Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication TORISEL is indicated for the treatment of advanced renal cell carcinoma. TORISEL ® is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma. ( 1 ) FDA label
Also known as temsirolimus, Bevacizumab, Temsirolimus (CCI-779)
Torisel · 11 trials · 10 indications
PFS was defined as the interval from the date of randomization until the earlier date of progression or death. Progression was assessed by independent imaging reviewers using Response Evaluation Criteria in Solid Tumors (RECIST) criteria which is 20% increase in sum of longest diameter of target lesions from nadir (the lowest blood counts); measurable increase in non-target lesion; appearance of new lesions.
Interval from date of randomization until documentation of progressive disease (PD) by an independent tumor assessment according to Response Evaluation Criteria in Solid Tumor (RECIST) or death for any reason whichever occurred first.
The primary objective of this study is to determine whether Velcade in combination with temsirolimus provides benefit to subjects with relapsed or refractory B-cell non-Hodgkin lymphoma as assessed by overall response rate (ORR) to therapy. ORR is the sum of patients with a Complete Response and Partial Response to therapy. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: 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 (OR) = CR + PR.
The primary objective of this study is to determine whether Velcade in combination with temsirolimus provides benefit to subjects with relapsed or refractory B-cell non-Hodgkin lymphoma as assessed by progression-free survival (PFS).
pharmacokinetic study
Time in months from start of study treatment to first randomization date of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the first randomization date plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was "Death").
Clinical benefit: confirmed complete response (CR) or partial response (PR) or had stable disease (SD) lasting at least 24 weeks. CR was the disappearance of all target lesions and nontarget lesions. PR was at least a 30 percent (%) decrease in sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD was having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).
MTD of the drug as part of combination therapy will be determined.
MTD of the drug as part of combination therapy will be determined.
MTD of the drug as part of combination therapy will be determined.
Percentage of participants with objective response (OR) based assessment of confirmed complete response(CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all lesions and no appearance of new lesions. Confirmed PR defined as \>=30 percent (%) decrease in sum of the longest dimensions (LD) of the target lesions taking as reference the baseline sum LD , without progression of nontarget lesions and no appearance of new lesions. Confirmed responses are those that persist on repeat imaging study \>=4 weeks after initial documentation of response.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period.
TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period. National Cancer Institute (NCI)-graded Common Toxicity Criteria (CTC) provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death).
Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs).
SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability / incapacity or are a congenital anomaly or birth defect in the offspring of a study subject. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported.
Temporary interruption of study treatment; may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor.
Dose reduction for individual participant allowed if a dose limiting toxicity (DLT) occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of \>3 weeks) unless investigator and medical monitor agree participant should remain in the study.
Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature \>39 degrees Celsius (C), respiratory rate \>20 beats per minute (bpm), and systolic and diastolic blood pressure (BP) \>200/110 millimeters of mercury (mmHg). Participants may be reported in more than 1 category.
Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category.
Measured as Complete response (CR), Very good partial response (VGPR), or Partial response (PR) on at least 2 occasions greater than or equal to (\>=) 4 weeks apart within first 12 weeks. CR=disappearance of all primary and metastatic lesions; Homovanillic acid, Vanillymandelic acid (HVA/VMA) normal; bone marrow immunocytology negative. VGPR=disappearance of all metastatic lesions (residual areas of uptake on bone permitted); 90 to 99 percent (%) decrease in primary disease measurement; HVA/VMA normal or both decreased \>90%. PR=at least 50% decrease in primary and metastatic disease. Number of bone sites decreased by at least 50%.
| Arm | Type | Description |
|---|---|---|
| 1 | EXPERIMENTAL | Bevacizumab 10 mg/kg intravenous (IV) q8wks + Temsirolimus 25 mg IV weekly |
| 2 | ACTIVE_COMPARATOR | Bevacizumab 10 mg/kg intravenous (IV) q8wks + Interferon-Alfa 9MU SC TIW |
| A | EXPERIMENTAL | - |
| B | EXPERIMENTAL | - |
| C | ACTIVE_COMPARATOR | - |
| Velcade plus Temsirolimus | EXPERIMENTAL | Velcade 1.6 mg/m2 weekly (days 1, 8, 15, and 22) Temsirolimus 25mg IV weekly (days 1, 8, 15, 22, and 29) Treat for up to 6 cycles, cycles are 35 days long. |
| triweekly then biweekly | EXPERIMENTAL | The arm A consisted of 2 cycles of triweekly TOMOX (standard dose 3mg/m2 of Raltitrexed in 15-minutes infusion, and 130mg/m2 of oxaliplatin in 2h infusion, every 3 weeks), followed by 2 cycles of biweekly TOMOX (2mg/m2 of Raltitrexed in 15-minutes infusion, and 85mg/m2 of oxaliplatin in 2h infusion, every 2 weeks). |
| biweekly then triweekly | EXPERIMENTAL | The arm B consisted of the reserve sequence starting with 2 cycles of biweekly TOMOX followed by 2 cycles of triweekly TOMOX regimen. |
| D | ACTIVE_COMPARATOR | bevacizumab (avastin) |
| A. | EXPERIMENTAL | - |
| B. | EXPERIMENTAL | - |
| Temsirolimus, cisplatin, erlotinib | EXPERIMENTAL | Cisplatin and temsirolimus will be administered weekly on days one and eight of a three week cycle. Erlotinib will be taken by mouth daily. |
| 1.0 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Bevacizumab | DRUG | Bevacizumab 10 mg/kg intravenous (IV) q8wks |
| Temsirolimus | DRUG | Temsirolimus 25 mg IV weekly |
| Interferon-Alfa 9MU | DRUG | Interferon-Alfa 9MU SC TIW |
| Sorafenib | DRUG | Subjects randomized to arm B will take sorafenib 400 mg (2 x 200 mg tablets) PO, BID (total daily dose of 800 mg). |
| temsirolimus (Torisel) | DRUG | Subjects randomized to arm A will receive temsirolimus (Torisel) 25 mg via IV infusion once weekly. This infusion is to be administered over a 30-60 minute period. Subjects are to be pre-treated with 25-50 mg IV diphenhydramine (or comparable IV antihistamine) approximately 30 minutes before temsirolimus infusion. |
| Temsirolimus (CCI-779) | DRUG | Temsirolimus 175 mg IV once a week for 3 weeks; followed by 75 mg IV once a week |
| Investigator's choice | DRUG | Any of the following single agent treatments: 1. Fludarabine 25 mg/m2 IV over 30 minutes daily for 5 consecutive days, every 28 days or oral administration, as appropriate. 2. Chlorambucil 0.1 (0.1-0.2) mg/kg PO daily for 3 to 6 weeks as required OR 0.4 (0.3 0.8) mg/kg PO every 21 to 28 days 3. Gemcitabine 1 gm/m2 IV over 30 minutes on days 1, 8 and 15 every 28 days or day 1 and day 8 every 21 days 4. Cyclophosphamide 300 (200-450) mg/m2 PO daily for 5 consecutive days every 21 to 28 days, OR 600 (400-1200) mg/m2 IV every 21 to 28 days 5. Cladribine 5 mg/m2 IV daily for 5 consecutive days, every 28 days for 2-6 cycles depending on response, 6. Etoposide 50 (50-150) mg/m2 IV daily for 3-5 days every 21 to 28 days OR 100 (50 300) mg/m2 PO daily for 3-5 days every 21 to 28 days 7. Prednisone 40 (20-60) mg/m2 PO daily or every other day 8. Dexamethasone 20(20-40) mg PO/IV daily for 5 consecutive days, every 14 - 28 day |
| Velcade | DRUG | Velcade, 1.6 mg/m2 weekly (days 1, 8, 15, and 22) |
| TOMOX | DRUG | - |
| Carboplatin | DRUG | Carboplatin is available as pre-mixed 10mg /ml aqueous solution- The starting dose is AUC 6 mg\*min/ml, iv infusion, every 3 weeks. |
| Paclitaxel | DRUG | Paclitaxel is available in multidose vials (30 mg/5ml;100mg/16.7 ml;300 mg/50ml)- The starting dose is 200 mg/m2, every 3 weeks |
| AG-013736 (axitinib) | DRUG | AG-013736 (axitinib) is available as 1mg, and 5 mg film-coated tablets for oral administration- The starting dose is 5 mg BID- |
| Bevacizumab (avastin) | DRUG | Bevacizumab intravenous \[IV\] infusion 5 mg/kg every two weeks until disease progression, intolerance or withdrawal of consent. |
| FOLFIRI (Irinotecan, leucovorin, 5-fluorouracil [5FU]) | DRUG | Irinotecan (180 mg/m²) intravenous infusion \[IV\] over 90 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion \[IV\] over 2 hours followed immediately by 5-FU bolus (400 mg/m²) intravenous \[IV\] and a subsequent 5-FU infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent. |
| FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]) | DRUG | Oxaliplatin (85 mg/m²) intravenous infusion \[IV\] over 120 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion \[IV\] over 2 hours followed by 5-FU IV bolus (400 mg/m²) and a subsequent 5-FU IV infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent. |
| Cisplatin | DRUG | Cisplatin at 30mg/m2 will be administered intravenously weekly on days one and eight of a three week cycle. Cisplatin will be given first over a 30 minute infusion with prehydration. |
| Erlotinib | DRUG | Erlotinib will be taken by mouth daily starting at 100mg. On days of cisplatin and temsirolimus infusions, erlotinib should be taken at least two hours after the beginning of the temsirolimus infusion. Dose escalation will follow the standard 3 by 3 design with three set dosing levels. Dose Level 1: Erlotinib 100mg Dose Level 2: Erlotinib 150mg Dose Level 3: Erlotinib 150mg |
| AG-013726 | DRUG | AG-013726 5 mg bid every 2 weeks |
| Torisel | DRUG | 60-minute intravenous (IV) infusion once weekly to pediatric subjects with advanced solid tumors. Part 1 is an ascending-dose study to evaluate the safety of IV temsirolimus given once weekly to subjects ages 1 to 21 years with advanced solid tumors disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available. (enrollment completed) Part 2 will be conducted in three groups of children with refractory or relapsed pediatric solid tumors. Subjects with the following tumor types will be enrolled: neuroblastoma, rhabdomyosarcoma, and high-grade gliomas. Subjects will receive IV temsirolimus once weekly until disease progression or unacceptable toxicity. |
Inclusion Criteria: * Histologically and/or cytologically confirmed to have advanced renal cell carcinoma (RCC) * Majority component of conventional clear-cell type is mandatory * At least 1 measurable lesion (per RECIST) Exclusion Criteria: * Prior systemic treatment for RCC * Evidence of curren...
Torisel is an investigational small molecule being studied for the treatment of adenocarcinoma. It is in Phase 1 clinical development for this oncology indication. The drug is not approved and remains under investigation.
Torisel is being developed by Pfizer, Inc., which trades on the New York Stock Exchange under the ticker PFE. The company is conducting clinical research on this small molecule for adenocarcinoma.
Torisel is in Phase 1 clinical development. It has completed one Phase 1 trial, which was an uncontrolled study. The drug remains investigational and is not yet approved for any use.
Torisel has been studied in one completed Phase 1 trial, NCT00106353, titled "Study Evaluating Biomarkers In Relapsed/Refractory Pediatric Solid Tumors." The trial enrolled 71 participants with adenocarcinoma and other neoplasms across multiple countries.
Torisel is not FDA approved. It is an investigational drug currently in Phase 1 clinical development for adenocarcinoma. The completed trial was uncontrolled and did not involve randomization or blinding.