Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication NEXAVAR is a kinase inhibitor indicated for the treatment of • Unresectable hepatocellular carcinoma ( 1.1 ) • Advanced renal cell carcinoma ( 1.2 ) • Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine treatment ( 1.3 ) 1.1 Hepatocellular Carcinoma NEXAVAR ® is indicated for the treatment of patients with unresectable hepatocellular carcinoma (HCC). FDA label
Also known as Nexavar, Sorafenib (BAY43-9006) Oral suspension, Sorafenib dose escalation, Sorafenib (BAY43-9006), BAY 43-9006, sorafenib (Nexavar)
Sorafenib · 70 trials · 63 indications
PFS was defined as the time from date of randomization to disease progression, radiological or death due to any cause, whichever occurs first. Per RECIST version 1.1, progressive disease was determined when there was at least 20% increase in the sum of diameters of the target lesions, taking as a reference the smallest sum on study (this included the baseline sum if that was the smallest sum on trial). In addition to a relative increase of 20%, the sum had demonstrated an absolute increase of at least 5 mm. Appearance of new lesions and unequivocal progression of existing non-target lesions was also interpreted as progressive disease. Participants without progression or death at the time of analysis were censored at their last date of evaluable tumor evaluation. Median and other 95% confidence intervals (CIs) computed using Kaplan-Meier estimates.
Overall Survival (OS) was defined as the time from date of randomization to death due to any cause.
Disease recurrence of HCC (intra or extra hepatic) was defined as the appearance of a new intrahepatic lesions fulfilling the American Association for the Study of Liver Diseases (AASLD) criteria of diagnosis of HCC or a new extra-hepatic lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.0. In addition to investigator assessment, all images were reviewed by an independent panel of radiologists. The calculation of the RFS was based on the independent evaluation of the scans. RFS was defined as the time from randomization to the first documented disease recurrence by independent radiological assessment or death due to any cause whichever occurred first. For subjects who had not recurred or died at the time of analysis, RFS was censored at their last date of evaluable scan before drop-out for any other reason than recurrence or death.
Overall survival (OS) was defined as the time from date of randomization to death due to any cause. Patients still alive at the time of analysis were censored at their last date of last contact.
Time to progression (TTP) was defined as the time from date of randomization to radiological progression / recurrence. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation.
The AUC(0-12h) was the observed AUC, calculated using a combination of linear and log trapezoidal rules, from pre-dose to 12 hours post-dose. The normalized AUC (AUC norm) is AUC (0-12h) divided by (dose \[mg\]/weight \[kg\]).
Cmax (maximum concentration) was measured at the time point at which the maximum concentration (Tmax) was observed. Cmin (minimum concentration) was measured at the time point at which the minimum concentration (Tmin) was observed.
Cmax (maximum concentration) was measured at the time point at which the maximum concentration (Tmax) was observed. Cmin (minimum concentration) was measured at the time point at which the minimum concentration (Tmin) was observed. The normalized variables (Cmax norm and Cmin norm) are the variables (Cmax and Cmin, see Primary Outcome Measure 2) divided by \[dose (mg)/weight (kg)\].
Overall Survival was defined as the time from date of starting treatment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
TTSP was defined as the time from randomization to the first documented symptomatic progression.
Overall survival determined as the time (days) from the date of randomization at start of study to the date of death, due to any cause. Outcome measure was assessed regularly, i.e. every 3 weeks for the first 24 weeks during treatment and every 4 weeks thereafter and approximately every 3 months during post-treatment.
Overall survival determined as the time (days) from the date of randomization at start of study to the date of death, due to any cause. Outcome measure was assessed regularly, i.e. every 3 weeks for the first 24 weeks during treatment and every 4 weeks thereafter and approximately every 3 months during post-treatment.
The disease control rate (DCR) was defined as the proportion of patients who did not meet Response Evaluation Criteria in Solid Tumors (RECIST) criteria for progressive disease (PD) at 8 weeks. Progressive disease was defined as at least a 20% increase in the sum of longest diameter (LD) of measured lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Criteria for response per the International Working Group for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Complete Response (CR) was defined as \</= 5% blasts in the bone marrow (BM) with peripheral blood (PB) demonstrating greater thatn 1x10\^9/L platelets with no detectable extramedullary disease. CR with incomplete recovery of PB counts (CRi) is the above criteria but neutrophil or platelet counts less than the stated values. Partial Response (PR) required all of the hematologic values for a CR but with a reduction of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.
Determine activity of sorafenib plus capecitabine on progression free survival (PFS) in patients with advanced colorectal cancer. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Progression Free Survival is defined as the time from enrollment to the date of first documented disease progression or death from any cause.
Progression free survival will be calculated from study entry to documented disease progression, death from any cause, or drop out due to toxicity, whichever occurs first.
Progression free survival will be calculated from study entry to documented disease progression, death from any cause, or drop out due to toxicity, whichever occurs first.
TTP is defined as the time (days) from randomization to radiological confirmed disease progression. Participants without progression at the time of analysis were censored at their last date of tumor evaluation.
Treatment toxicities assessed by CTCAE v3.0 were stratified by cycle - patients on Cycle 1, and patients on Cycles 2-5 or more. 50 patients were reviewed for toxicities for Cycle 1, and all 50 patients experienced at least one adverse event during this time period.
Time from randomization to the first documented disease progression by radiological or pathologic assessment or death due to any cause whichever occurred first. For patients who had not progressed or died at the time of analysis, PFS was censored at the date of their last evaluable tumor scan.
Tolerability will be defined as successful completion of the dose level without experiencing Grade 3 or 4 toxicity.
Best Response (Response Rate) of a subject was defined as the proportion of patients with confirmed Complete Response (CR) or Partial Response (PR) as their best response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed CR was defined as disappearance of tumor and PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes.
Tumor Response of a subject was defined as the best tumor response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed Complete Response (CR) was defined as disappearance of tumor, Partial Response (PR) was defined as a decrease of at least 30% in the sum of target lesions, Stable Disease (SD) was defined as steady state of disease, and Progressive Disease (PD) was defined as at least a 20% increase in the sum of measured lesions or appearance of new lesions.
Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.
The primary outcome was the proportion of patients who achieved progression free survival (PFS) of five months. PFS was defined as time to progression or any-cause mortality, whichever came first.
The proportion of patients with progression-free survival at 2 years. Progression-free survival is measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death on study. Progression is defined in RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation
Best Overall Response (BOR): Best tumor response achieved during or within 30 days after active therapy confirmed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR): The disappearance of all target and non-target lesions. Partial response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD was defined as steady state of disease, PD was defined as an increase of at least 20% increase in the sum of the LD of target lesions or appearance of new lesions.
Number of subjects with metastatic breast cancer treated with single agent BAY43-9006 who had best overall response assessed as complete response (CR) or partial response (PR) as per Modified World Health Organization (WHO) Tumor Response Criteria.
Objective response rate of sorafenib assessed as the proportion of subjects with confirmed complete or partial response as per modified World Health Organization (WHO) criteria.
Establish the recommended phase II dose of the combination of topotecan and sorafenib in children. This will be the maximum tolerated dose.
Primary endpoint: Define the recommended phase II dose (RPTD) by the number of dose limiting toxicity events (recorded during treatment cycle 1 and 2)
The number of patients who had a DLT during the dose finding/confirming portion (Phase I) of the trial for the safety of the combination of sorafenib, vorinostat, and bortezomib.
Evaluate the overall response rate of patients receiving therapy. Patients are considered as having a response if their overall response is Partial Response or better. The percentage of patients achieving this and the exact 95% confidence interval will be calculated. Responses will be defined using the response criteria determined by the International Working Group for AML.
MTD is defined as highest dose level in which 6 patients treated with at most 1 experiencing a dose limiting toxicity (DLT) during 1st cycle. One cycle of therapy is 7 days of azacitidine (AZA) and 28 days of sorafenib. Starting dose of Sorafenib is 200 mg twice a day azacitidine
To determine the maximally tolerated dose of weekly bortezomib in combination with 400mg twice daily sorafenib.
To document and summarize the toxicities of weekly bortezomib in combination with 400mg twice daily sorafenib
Safety and tolerability of sorafenib in combination with radiation and temozolomide chemotherapy in patients with newly diagnosed high grade glioma
Number of dose limiting toxicities and number with adverse events. Dose-escalation schedule comprising 6 to 12 patients (see schema). This sample size is based on a traditional 3+3 cohort design with escalating doses of sorafenib in combination with 50 Gy of conformal radiotherapy delivered in 25 fractions (200 cGy per fraction). Based on preclinical data regarding the radiobiology of sorafenib,33, 36 sorafenib will be initiated at a dose of 200 mg twice daily, followed by 200 mg Q AM/400 mg Q PM for the 2nd cohort, followed by 400 mg bid for the 3rd cohort. Since 400 mg bid is the well established MTD for sorafenib monotherapy in patients with renal cell carcinoma and hepatocellular carcinoma, the dose will not be escalated above this level even if DLT is not observed. Dose level escalation will be determined based on DLTs observed from initiation of sorafenib/RT until time of surgery.
Response rate of participant to treatment
The MTD is based upon dose-limiting (DLTs) experienced during Cycle 1 of treatment. The MTD is the maximum dose level at which 0/6 or 1/6 patients experience DLT. Using Common Toxicity Criteria for Adverse EVents (CTCAE) version 3.0, DLTs are defined as any Grade 4 hematologic toxicity, or Grade 3 or 4 non-hematologic toxicity. A DLT will not be considered to have occurred in the case of a grade 3 or 4 allergic reaction due to cetuximab.
The proportion of patients for whom the best overall response is complete response (CR), partial response (PR) or stable disease (SD). A CR occurs when all lesions disappear; whereas, a PR is indicated when there is at least a 30% decrease in the sum of the longest diameters (LD) of the target lesion. A PD (progressive disease) occurs when there is at least a 20% increase in the sum of the LD relative to the smallest sum LD recorded since treatment is initiated. Disease is considered stable if there is no response and no PD. If follow-up assessments are not available, the best overall response is unevaluable.
The percentage of patients who experience an objective benefit from treatment, determined by the treating physician after reviewing key laboratory values from blood and urine.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response Rate (ORR) = Percentage of Patients Who Experience an Objective Response (CR+ PR) to Treatment. In oncology, this outcome measure is reported for all patients treated at the same dose level and is not separated into Phase I and Phase II. The phase I and phase II results are not separated out as the timing of their enrollment (early in phase 1 or later phase II) is not relevant to the outcome measure.
MTD was determined by testing increasing doses up to 400 mg twice daily (bid) on dose escalation cohorts 1 to 3 with 3 patients each. MTD reflects highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity (DLT) in more than 30% of patients; e.g., hematologic toxicities like Common Toxicity Criteria (CTC) Grade 4 Neutropenia in specific conditions, platelets \< 25,000 cells/mL; specific non-hematologic/biochemical toxicities CTC Grade 3 or 4; additionally, any toxicity considered by the investigator severe enough was designated a DLT); CTC Version 2 were used.
Participants are considered at risk for toxicity if participants had a lab measurement for the toxicity \>= National Cancer Institute Common Toxicity Criteria (NCI CTC) Grade 3 as defined by the NCI CTC version 2; SGOT: Serum Glutamic-Oxaloacetic Transaminase, SGPT: Serum Glutamic-Pyruvic Transaminase, AST: Aspartate Aminotransferase, ALT: Alanine Aminotransferase.
| Arm | Type | Description |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) + Capecitabine | EXPERIMENTAL | Capecitabine was administered orally at a dose of 1,000 milligram per square meter (mg/m\^2) twice daily (12 hours apart) on Days 1 through 14 of each 21-day cycle. Sorafenib was administered orally at a dose of 600 mg (200 mg in the morning, 400 mg in the evening) daily, continuously (that is, Days 1 to 21, inclusive). A treatment cycle consisted of 21 days. If tolerability criteria were met for a subject, capecitabine dose was escalated to 1,250 mg/m\^2 twice daily and sorafenib dose to a total daily dose of 800 mg for that subject. |
| Placebo + Capecitabine | PLACEBO_COMPARATOR | Capecitabine was administered orally at a dose of 1,000 mg/m\^2 twice daily (12 hours apart) on Days 1 through 14 of each 21-day cycle. Placebo matching to sorafenib was administered orally, 3 tablets (1 tablet in the morning, 2 tablets in the evening) daily, continuously (that is, Days 1 to 21, inclusive). A treatment cycle consisted of 21 days. If tolerability criteria were met for a subject, capecitabine dose was escalated to 1,250 mg/m\^2 twice daily and placebo dose to a total daily dose of 4 tablets (2 tablets twice daily) for that subject. |
| Sorafenib (Nexavar, BAY43-9006) + Erlotinib (Tarceva) | EXPERIMENTAL | Participants received sorafenib 400 mg twice daily (bid) and erlotinib 150 mg tablet once daily (qd) |
| Sorafenib (Nexavar, BAY43-9006) + Placebo | ACTIVE_COMPARATOR | Participants received sorafenib 400 mg twice daily (bid) and matching erlotinib placebo 150 mg tablet once daily (qd) |
| Sorafenib (Nexavar, BAY43-9006) | EXPERIMENTAL | Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) |
| Placebo | PLACEBO_COMPARATOR | Participants received 2 tablets of placebo orally twice daily (BID) |
| Sorafenib (Nexavar, BAY43-9006) + GC | EXPERIMENTAL | Up to 6 cycles (21 days per cycle) of gemcitabine (G) and cisplatin (C) with sorafenib. Day 1: gemcitabine 1250 mg/ m\^2 infusion (IV), followed by cisplatin 75 mg/ m\^2 IV; Day 8: gemcitabine 1250 mg/ m\^2 IV; Days 1-21: sorafenib 2 tablets (200 mg) taken orally (po) twice daily (bid). If the patient had radiological evidence of stable disease (SD) or better after completing up to 6 cycles in the Chemotherapy Phase, the patient could continue to Maintenance Phase, during which sorafenib was administered 400 mg bid until criteria for withdrawal were met. |
| Placebo + GC | PLACEBO_COMPARATOR | Up to 6 cycles (21 days per cycle) of gemcitabine (G) and cisplatin (C) with placebo. Day 1: gemcitabine 1250 mg/ m\^2 infusion (IV), followed by cisplatin 75 mg/ m\^2 IV; Day 8: gemcitabine 1250 mg/ m\^2 IV; Days 1-21: placebo 2 tablets po bid. If the patient had radiological evidence of SD or better after completing up to 6 cycles in the Chemotherapy Phase, the patient could continue to Maintenance Phase, during which 2 placebo tablets were administered bid until criteria for withdrawal were met. |
| Arm 1 | EXPERIMENTAL | - |
| Sorafenib | EXPERIMENTAL | Sorafenib 400 mg By Mouth Twice Daily for 28 Days. |
| Azacytidine + Sorafenib | EXPERIMENTAL | Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously. |
| Sorafenib plus Doxorubicin | EXPERIMENTAL | Doxorubicin 60 mg/m2 IV on Day 1 of each 3 weeks cycle until unacceptable toxicity Sorafenib 400 mg PO BID or last dose patient from previous sorafenib based therapy, until unacceptable toxicity or disease progression, after which sorafenib can be continued as a single agent. |
| Sorafenib Plus Capecitabine (SorCape) | EXPERIMENTAL | Sorafenib 200-400 mg PO twice daily on days 1-21 (dose escalation schema) plus Capecitabine 1000 mg/m2 PO twice daily on days 1-14 repeated every 21 days. Single arm study. |
| sorafenib combined with chemotherapy | EXPERIMENTAL | this trial is designed single arm. all the subjects enrolled will receive the experimental intervention,ie. sorafenib+gemcitabine+cisplatin. |
| Gemcitabine and Cisplatin plus Sorafenib | EXPERIMENTAL | This is a non-randomized, open label, single institution, phase II study of gemcitabine and cisplatin plus sorafenib for the treatment of patients with advanced or biliary tract carcinomas naïve to systemic therapy. |
| Sorafenib (Nexavar, BAY43-9006) + TACE | EXPERIMENTAL | Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Patients were then also treated with Transarterial Chemoembolization (TACE) performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of sorafenib, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.) |
| Placebo + TACE | PLACEBO_COMPARATOR | Placebo was to be orally administered as 2 tablets bid (twice daily). Patients were then also treated with TACE performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of placebo, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.) |
| sorafenib and drug eluting beads | EXPERIMENTAL | single arm |
| Intra-Patient Dose Escalation: Sorafenib | EXPERIMENTAL | All patients will receive a starting dose of sorafenib 400 mg by mouth twice daily. At four weeks, all patients who have not experienced Grade 3 or 4 toxicity will undergo dose escalation using a treatment schedule of days 1-5 days of each week. Doses will continue to be escalated every 4 weeks depending on tolerability and tumor response. |
| Sorafenib + Temozolomide | EXPERIMENTAL | Subjects receive 400mg of Sorafenib twice daily and 50mg/m\^2 of Temozolomide once daily Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changes in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure |
| Combination Therapy | EXPERIMENTAL | In the combined modality portion of the study, patients were administered: Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily Patients took a four week break before beginning follow-up systemic therapy: Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months |
| Chemotherapy plus sorafenib | EXPERIMENTAL | Gemcitabine 1000 mg/m2 weekly x 2 weeks plus carboplatin AUC (Area under curve) 5 every 3 weeks plus sorafenib x 6 cycles then maintenance sorafenib alone |
| Paclitaxel/Carboplatin/Sorafenib | ACTIVE_COMPARATOR | Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV, Day 1 Sorafenib 400mg PO bid |
| Paclitaxel/carboplatin | ACTIVE_COMPARATOR | Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV |
| A | PLACEBO_COMPARATOR | Chemotherapy + Placebo |
| B | ACTIVE_COMPARATOR | Chemotherapy + Sorafenib |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg then 600 mg | EXPERIMENTAL | Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression (= first intervention period, 5.7 months \[median\] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months \[median\]) on a continuous basis. |
| First Interferon then Sorafenib (Nexavar, BAY43-9006) 400 mg | ACTIVE_COMPARATOR | Interferon (IFN) α-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months \[median\]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period.After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months \[median\]). |
| Sorafenib + Dacarbazine | EXPERIMENTAL | Dacarbazine 1000 mg/m\^2 on day one of repeated 21 day cycles, in combination with daily continuous oral sorafenib (Nexavar, BAY 43-9006), 400 mg twice a day (bid) |
| Sorafenib + Doxorubicin | EXPERIMENTAL | "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
| Placebo + Doxorubicin | ACTIVE_COMPARATOR | "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
| Arm 2 | PLACEBO_COMPARATOR | - |
| Sorafenib 400 mg b.i.d. | EXPERIMENTAL | Sorafenib (Nexavar, BAY43-9006) 400 mg administered bis in die (bid, twice a day) |
| Arm A: Pazopanib with Radium-223 | EXPERIMENTAL | No prior targeted therapy * Pazopanib oral, daily and at predetermined dosage per cycle * Radium-223 predetermined dosage via IV, per cycle |
| Arm B: Sorafenib with Radium-223 | EXPERIMENTAL | At least one line of prior targeted therapy: * Sorafenib at predetermined dosage, mouth twice daily * Radium-223 predetermined dosage via IV, per cycle |
| Sorafenib (Nexavar, BAY43-9006) & Levothyroxine | EXPERIMENTAL | Sorafenib be administrated without and with levothyroxine orally |
| Combination Chemotherapy | EXPERIMENTAL | Combination Chemotherapy: Topotecan and Sorafenib. Participants will receive the treatment in cycles. Every cycle is 28 days long. For the first cycle participants will get the chemotherapy drugs: * Topotecan PO (by mouth) once daily on days 1-5 and days 8-12 * Sorafenib PO (by mouth) twice daily (BID), continuously on days 2-28 of cycle one and days 1-28 on each additional cycle. * Level -1: Topotecan 1.0 mg/m\^2: Sorafenib 100 mg/m\^2 BID * Level -2: Topotecan 0.8 mg/m\^2: Sorafenib 100 mg/m\^2 BID * Level 1: Topotecan 1.0 mg/m\^2: Sorafenib 150 mg/m\^2 BID * Level 2: Topotecan 1.4 mg/m\^2: Sorafenib 150 mg/m\^2 BID * Level 3: Topotecan 1.4 mg/m\^2: Sorafenib 200 mg/m\^2 BID * Level 4: Topotecan 1.8 mg/m\^2: Sorafenib 200 mg/m\^2 BID |
| Sorafenib + Eribulin | EXPERIMENTAL | - |
| vinflunine + sorafenib | EXPERIMENTAL | Single arm study. |
| sorafenib, vorinostat and bortezomib | EXPERIMENTAL | Escalating cohorts of sorafenib, vorinostat and bortezomib |
| Azacitidine + Sorafenib | EXPERIMENTAL | Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days; Sorafenib 200 mg orally twice a day. |
| Dose Escalation | EXPERIMENTAL | - |
| Research Participants | OTHER | Participants treated with sorafenib, cytarabine and clofarabine. |
| Sorafenib and RAD001 | EXPERIMENTAL | * Since we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have neuroendocrine tumors, not everyone who participates in this research study will receive the same dose of the study drug. The dose the participant will be given will depend on the number of participants who have been enrolled in the study. * Each treatment cycle lasts 28 days. Participants will take RAD001 orally once a day in the morning. Participants will take sorafenib orally twice daily. * Participants will remain on this research study as long as they continue to benefit from the study medications. |
| Sorafenib dose titration | EXPERIMENTAL | - |
| Phase I | EXPERIMENTAL | - |
| Sorafenib and irinotecan | EXPERIMENTAL | - |
| Arm 3 | EXPERIMENTAL | - |
| Erlotinib/Sorafenib | EXPERIMENTAL | Patients will receive erlotinib 150 mg once daily by mouth and sorafenib 400 mg twice daily by mouth. The study will begin with a 2-week run-in period (which will begin on Day 14 of the study, and continue through Day 1 of the study), in which erlotinib will be dosed alone at 150 mg once daily. Patients will continue taking erlotinib as a single agent at 150 mg once daily through Day 1. After the 2-week run-in period, patients will receive continuous dosing of both agents (erlotinib 150 mg once daily and sorafenib 400 mg twice daily) in cycles of 28 days each. Toxicity will be assessed every cycle (every 4 weeks) for all patients. Because this is not an efficacy study, restaging tumor measurements will be at the discretion of the physician every 8 weeks during treatment. Patients with objective response or stable disease will continue therapy; patients with disease progression or unacceptable toxicity will be discontinued from the study. |
| Phase I: 200mg Sorafenib+2DOC | EXPERIMENTAL | Cohort 1: 200mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib |
| Phase I: 400mg Sorafenib BID+2DOC | EXPERIMENTAL | Cohort 2: 400mg Sorafenib+2DOC Oxaliplatin + Oral Capecitabine + Sorafenib |
| Phase II: Pancreatic Cancer | EXPERIMENTAL | Oxaliplatin + Oral Capecitabine + Sorafeni |
| Phase II: Biliary Tract Cancer | EXPERIMENTAL | Oxaliplatin + Oral Capecitabine + Sorafeni |
| Sorafenib, Bevacizumab & Paclitaxel | EXPERIMENTAL | Paclitaxel is given as i.v infusion over 60 min on days 1, 8, 15 every 28 days. Sorafenib is given orally starting with cycle 1 day 2. Bevacizumab is given as i.v infusion on days 1 and 15 every 28 days. |
| Cetuximab + sorafenib | EXPERIMENTAL | Cetuximab will be given at standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib will be given at 200mg/m2 twice daily. |
| Intervention | EXPERIMENTAL | The trial was designed as a single-arm Phase I/II study of sorafenib and bortezomib with dose optimization in initial patients. Phase I consisted of cohorts of 3 patients at each of three dose levels. Patients received bortezomib (Dose Level 1 - 1.3 mg/m2; Dose Level 2 - 1.6 mg/m2) by IV bolus on days 1, 8, 15, and 22 of each 5-week cycle with continuous oral dosing of sorafenib at 200 mg twice daily. Dose level 3 was planned as bortezomib 1.6 mg/m2 IV bolus on days 1, 8, 15, and 22 with sorafenib 400 mg by mouth twice daily throughout each 5-week cycle. |
| RAD001 and Sorafenib | EXPERIMENTAL | RAD001 and Sorafenib |
| Arm 4 | EXPERIMENTAL | - |
| Arm 5 | EXPERIMENTAL | - |
| Arm 6 | EXPERIMENTAL | - |
| Sorafenib 100 mg (50-mg tablet) | EXPERIMENTAL | Dose-escalation cohort 1: Sorafenib (Nexavar, BAY43-9006) 100 mg twice daily (50-mg tablet). Treatment were planned until primary completion date (PCD). |
| Sorafenib 200 mg (50-mg tablet) | EXPERIMENTAL | Dose-escalation cohort 2: Sorafenib (Nexavar, BAY43-9006) 200 mg twice daily (50-mg tablet). Treatment were planned until primary completion date (PCD). |
| Sorafenib 400 mg (50-mg tablet) | EXPERIMENTAL | Dose-escalation cohort 3: Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (50-mg tablet). Treatment were planned until primary completion date (PCD). |
| Sorafenib 400 mg (200-mg tablet) | EXPERIMENTAL | Dose-escalation cohort 4: Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (200-mg tablet). Treatment were planned until primary completion date (PCD). |
| Sorafenib 400 mg (Expansion) | EXPERIMENTAL | Dose-expansion cohort: Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (200-mg tablet) expansion. Treatment were planned until primary completion date (PCD). 25 of 119 participants from the Expansion Phase, were still on the treatment as of 31 May 2005. Of these, 6 subjects were continuing to receive sorafenib in combination with carboplatin and/or paclitaxel and 19 subjects were receiving single-agent sorafenib until 18 Sep 2008. |
| Name | Type | Description |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | DRUG | Capecitabine was administered orally at a dose of 1,000 milligram per square meter (mg/m\^2) twice daily (12 hours apart) on Days 1 through 14 of each 21-day cycle. Sorafenib was administered orally at a dose of 600 mg (200 mg in the morning, 400 mg in the evening) daily, continuously (that is, Days 1 to 21, inclusive). A treatment cycle consisted of 21 days. If tolerability criteria were met for a subject, capecitabine dose was escalated to 1,250 mg/m\^2 twice daily and sorafenib dose to a total daily dose of 800 mg for that subject. |
| Placebo | DRUG | Capecitabine was administered orally at a dose of 1,000 mg/m\^2 twice daily (12 hours apart) on Days 1 through 14 of each 21-day cycle. Placebo matching to sorafenib was administered orally, 3 tablets (1 tablet in the morning, 2 tablets in the evening) daily, continuously (that is, Days 1 to 21, inclusive). A treatment cycle consisted of 21 days. If tolerability criteria were met for a subject, capecitabine dose was escalated to 1,250 mg/m\^2 twice daily and placebo dose to a total daily dose of 4 tablets (2 tablets twice daily) for that subject. |
| Capecitabine | DRUG | Capecitabine was administered orally at a dose of 1,000 milligram per square meter (mg/m\^2) twice daily (12 hours apart) on Days 1 through 14 of each 21-day cycle.days. If tolerability criteria were met for a subject, capecitabine dose was escalated to 1,250 mg/m\^2 twice daily, |
| Erlotinib (Tarceva) | DRUG | Erlotinib 150 mg once daily |
| Nexavar (Sorafenib, BAY43-9006) | DRUG | Sorafenib 400 mg twice daily (BID) |
| Gemcitabine | DRUG | Chemotherapy component; Gemcitabine 1250 mg/m\^2 IV |
| Cisplatin | DRUG | Chemotherapy component; Cisplatin 75 mg/m\^2 IV |
| Sorafenib | DRUG | 400 mg By Mouth Twice Daily for 28 Days. |
| Azacytidine | DRUG | 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle. |
| Sorafenib (Nexavar,BAY43-9006) | DRUG | Sorafenib 400 mg will be administered orally,twice daily in a 28 day cycle |
| Doxorubicin | DRUG | - |
| Sorafenib Plus Capecitabine (SorCape) | DRUG | Sorafenib 200-400 mg PO twice daily on days 1-21 (dose escalation schema) plus Capecitabine 1000 mg/m2 PO twice daily on days 1-14 repeated every 21 days |
| LC Bead-TACE | PROCEDURE | LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period |
| Sorafenib and Temozolomide | DRUG | Temozolomide (50 mg per meter-squared of body surface area)every day by mouth in combination with sorafenib. Sorafenib will be taken by mouth twice every day. The dose of sorafenib will be 400 mg (2 x 200mg tablets). |
| Radiation Therapy | RADIATION | 2 Gy/fraction, single daily fractions M-F, to 60 Gy total |
| Temozolomide | DRUG | In Combined Modality Therapy, administered as 75 mg/m2 by mouth once daily In follow-up systemic therapy, administered as 150 mg/m2 by mouth on days 1-5 every 28 days for 6 cycles |
| Carboplatin | DRUG | Carboplatin will be given on day 1 to an AUC of 5. |
| Paclitaxel | DRUG | Paclitaxel |
| Interferon | DRUG | Interferon |
| Sorafenib (Nexavar, BAY43-9006) + Dacarbazine (DTIC) | DRUG | Dacarbazine 1000 mg/m\^2 on day one of repeated 21 day cycles, in combination with daily continuous oral sorafenib (Nexavar, BAY 43-9006), 400 mg twice a day (bid) |
| Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin | DRUG | Multi kinase inhibitor plus Chemotherapy |
| Doxorubicin/Placebo | DRUG | Chemotherapy plus Placebo |
| Pazopanib | DRUG | - |
| Radium-223 | DRUG | - |
| Levothyroxine | DRUG | Single dose of 300 mcq orally from Period 2 Day 1 to Period 2 Day 14 |
| Topotecan | DRUG | Topotecan will be given by mouth as outlined in treatment arm. |
| Eribulin | DRUG | Eribulin: 1.4 mg/m2 as an intravenous infusion on Days 1 and 8 of each 21-day cycle. |
| Vinflunine | DRUG | Vinflunine (Javlor®, Pierre Fabre Pharma): 320 mg/m2 I.V., day 1, repeated every 21 days for patients with PS 0, adequate renal (creatinine clearance \>60 ml/min) and hepatic function (as described in the inclusion criteria). PLEASE NOTE THAT THE 320 mg/m2 ARM IS CLOSED FOR RECRUITMENT. For patients with PS 1, or age 75 to 80 years, or exposed to radiation of the lower pelvis region, or with impaired renal function (creatinine clearance 40-60 ml/min) but adequate hepatic function (as described in the inclusion criteria), the dose of vinflunine is 280 mg/m2 I.V. day 1, repeated every 21 days. |
| sorafenib, vorinostat and bortezomib | DRUG | Escalating dose cohorts of sorafenib, vorinostat and bortezomib. The first cohort will receive sorafenib from day 1 to 14, vorinostat will be given on days 1-4 and 8-12, and bortezomib will be given on days 1 and 8. This will be followed by 7 days of rest. Therefore each cycle will be 21 days. |
| Azacitidine | DRUG | 75 mg/m\^2 subcutaneously (SQ) or by vein (IV) daily for 7 days per 28 day cycle. |
| bortezomib | DRUG | Given intravenously on days 1, 8 and 15 of each 28 day cycle |
| Cytarabine | DRUG | Please see Detailed Description. |
| Clofarabine | DRUG | Please see Detailed Description. |
| RAD001 | DRUG | Taken orally once daily in the morning |
| Sorafenib dose escalation | DRUG | Sorafenib dose escalation scheme: 3 first patients: 200 mg/d, if dose limiting toxicities (DLT) not reached: 3 patients at 200 mg BID, if no DLT reached: 3 patients at 400 mg bid |
| Nexavar (Sorafenib) and irinotecan (Campto) | DRUG | Sorafenib administrated continuously orally 400 mg twice daily (a daily total dose of 800 mg). Irinotecan 180 mg/m² will be administered IV for 90 minutes every 2 weeks. The first dose of sorafenib will be administered after the first perfusion of irinotecan 180 mg/m² at the first infusion |
| Erlotinib | DRUG | 150 mg once daily by mouth |
| Oxaliplatin | DRUG | On days 1 and 15 of each 28 day treatment cycle, patients receive oxaliplatin 85 mg/m2 as a 2-hour IV infusion. Following the infusion of oxaliplatin, the infusion line should be flushed with Dextrose 5% in Water. |
| Cetuximab | DRUG | Cetuximab will be given at standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. |
| Sirolimus | DRUG | - |
| Bevacizumab | DRUG | Bevacizumab 2.5 mg/kg intravenously |
| Sorafenib (BAY43-9006, Nexavar) | DRUG | All subjects were given a open-label, single dose of 400mg sorafenib |
| Sorafenib 100 mg (50-mg tablet) | DRUG | Sorafenib (Nexavar, BAY43-9006) 100 mg twice daily (50-mg tablet) |
| Sorafenib 200 mg (50-mg tablet) | DRUG | Sorafenib (Nexavar, BAY43-9006) 200 mg twice daily (50-mg tablet) |
| Sorafenib 400 mg (50-mg tablet) | DRUG | Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (50-mg tablet) |
| Sorafenib 400 mg (200-mg tablet) | DRUG | Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (200-mg tablet) |
| Sorafenib 400 mg (Expansion) | DRUG | Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (200-mg tablet) expansion |
Inclusion Criteria: * Age is \>=18 years * Subject has histologically or cytologically confirmed HER2-negative adenocarcinoma of the breast. HER2 status should be determined by an accredited laboratory * Subject has locally advanced or metastatic disease; locally advanced disease must not be amenab...
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Sorafenib is an oral small molecule studied in several cancers, including acute myeloid leukemia, advanced solid tumors, bladder cancer, breast cancer, and other cancers. It is also being evaluated in metastatic renal cell carcinoma and thyroid carcinoma. Sorafenib is given as a tablet or oral suspension in clinical trials.
Sorafenib targets RAF1, PDGFRB, BRAF, KIT, FLT3, and RET. It is a small molecule inhibitor that blocks these kinases, which are involved in tumor cell signaling and angiogenesis. This multi-target profile is being studied across various cancer types.
Sorafenib is developed by Bayer AG, which trades on the OTC market under the ticker BAYRY. Bayer AG is the sponsor of the clinical trials evaluating sorafenib in oncology indications.
Sorafenib is in Phase 2 clinical development. It is an investigational agent and has not been approved by the FDA for the indications currently being studied. The Phase 2 trials are evaluating its use in acute myeloid leukemia, thyroid carcinoma, and other cancers.
Sorafenib has been studied in multiple clinical trials, including NCT02406521 in metastatic renal cell carcinoma, NCT02332031 in healthy male subjects for drug interactions, NCT02196857 in acute myeloid leukemia and high-risk myelodysplastic syndrome with FLT3-ITD mutation, and NCT02114658 in Japanese patients with anaplastic or medullary thyroid carcinoma.
Yes, Sorafenib is also known as Nexavar. Other names include BAY43-9006 and Sorafenib (Nexavar, BAY43-9006). These terms refer to the same drug, which is developed by Bayer AG.