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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 (CCI-779), temsirolimus (Torisel), Torisel, CCI-779
Temsirolimus · 8 trials · 9 indications
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).
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.
Toxicity of CCI-779 (Temsirolimus) and bortezomib (Velcade) in patients with multiple myeloma.
Response rate of PR or better to the combination treatment of CCI-779 (Temsirolimus) and bortezomib (Velcade) in patients with relapsed or refractory multiple myeloma
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 | - |
| 2 | EXPERIMENTAL | - |
| 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. |
| 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. |
| CCI779 and Bortezomib Phase I/II | EXPERIMENTAL | In Phase I part, 15 or 25 mg temsirolimus (CCI-779)and 1·3 or 1·6 mg/m² bortezomib was given once a week.In Phase II, patients received intravenous temsirolimus once a week on days 1, 8, 15, 22, and 29 for a cycle of 35 days, and intravenous bortezomib once a week on days 1, 8, 15, and 22 for a cycle of 35 days, the MTD ascertained in the Phase I part. |
| 1.0 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| 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) |
| Temsirolimus | DRUG | Temsirolimus 25mg IV weekly (days 1, 8, 15, 22, and 29) |
| CCI-779 | DRUG | - |
| 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 |
| Bortezomib | DRUG | Given by injection once a week for 4 weeks (a cycle equals 5 weeks) for up to 8 cycles |
| 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 confirmed diagnosis of mRCC (regardless of histology or nephrectomy status) with well-documented Radiological PD by RECIST criteria or clinical PD as judged by the investigator while receiving first-line sunitinib therapy. Subjects must have at least 1 cycle of ...
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Temsirolimus is an oncology drug studied in advanced renal cell carcinoma, renal cell carcinoma, lymphoma, non-Hodgkin lymphoma, and triple negative breast cancer. It has been evaluated as a second-line therapy in patients with advanced renal cell carcinoma who failed first-line sunitinib, and in combination regimens for relapsed or refractory non-Hodgkin lymphoma and solid tumors.
Temsirolimus targets FKBP1A. It is a small-molecule inhibitor that binds to FKBP1A, and this interaction is central to its mechanism of action as an mTOR inhibitor in oncology. The target class is inhibitor, and the drug is being developed for cancers including renal cell carcinoma and lymphoma.
Temsirolimus is developed by Pfizer, Inc., which trades under the ticker PFE. Pfizer is the company responsible for the clinical development of temsirolimus across its studied oncology indications, including renal cell carcinoma, lymphoma, and triple negative breast cancer.
Temsirolimus is in Phase 2 development. It is an investigational small-molecule drug and is not described as approved. Clinical trials have included Phase 1, Phase 2, and Phase 3 studies, with the most advanced completed trial being a Phase 3 study in renal cell carcinoma.
Temsirolimus has been studied in completed trials including NCT01281917, a Phase 2 study of Velcade and temsirolimus for relapsed or refractory non-Hodgkin lymphoma; NCT00998036, a Phase 1 study in triple negative breast cancer; NCT00494091, a Phase 2 study in advanced renal cell carcinoma; and NCT00474786, a Phase 3 study versus sorafenib in advanced renal cell carcinoma.
Yes, temsirolimus is also known as CCI-779 and by the brand name Torisel. These names refer to the same small-molecule drug developed by Pfizer for oncology indications including renal cell carcinoma, lymphoma, and triple negative breast cancer.