Phase I Trial of Bevacizumab and Temsirolimus in Combination With 1) Carboplatin, 2) Paclitaxel, 3) Sorafenib for the Treatment of Advanced Cancer
2 other identifiers
interventional
278
1 country
1
Brief Summary
The goal of this clinical research study is to find the highest tolerable dose of the combination of bevacizumab (Avastin) and temsirolimus (Torisel) that can be given with 1 of 3 other study drugs --carboplatin (Paraplatin), paclitaxel (Taxol), or sorafenib (Nexavar). The safety of these drug combinations will also be studied.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2010
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 19, 2010
CompletedFirst Submitted
Initial submission to the registry
August 20, 2010
CompletedFirst Posted
Study publicly available on registry
August 23, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2026
CompletedApril 16, 2026
April 1, 2026
15.7 years
August 20, 2010
April 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum Tolerated Dose (MTD)
MTD defined by dose-limiting toxicities (DLTs) that occur during the first four weeks of therapy. DLT defined as any grade 3 or 4 non-hematologic toxicity as defined in NCI CTC v4.0.
4 weeks
Secondary Outcomes (3)
Anti-Tumor Efficacy of Temsirolimus and Bevacizumab When Used in Combination with Carboplatin
56 days
Anti-Tumor Efficacy of Temsirolimus and Bevacizumab When Used in Combination with Paclitaxel
56 days
Anti-Tumor Efficacy of Temsirolimus and Bevacizumab When Used in Combination with Sorafenib
56 days
Study Arms (3)
Carboplatin Group
EXPERIMENTALCarboplatin: Starting dose AUC 2 by vein on day 1 of a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
Paclitaxel Group
EXPERIMENTALPaclitaxel: Starting dose 30 mg/m2 given by vein on day 1 of a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
Sorafenib Group
EXPERIMENTALSorafenib: Starting dose 200 mg by mouth daily for a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
Interventions
Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle.
Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
Starting dose 30 mg/m2 given by vein on day 1 of a 21 day cycle.
Starting dose 200 mg by mouth daily for a 21 day cycle.
Starting dose AUC 2 by vein on day 1 of a 21 day cycle.
Eligibility Criteria
You may qualify if:
- Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
- Patients must have been off previous chemotherapy or radiotherapy for the three weeks prior to entering this study. Six weeks will be required if the patient has received therapy which is known to have delayed toxicity (mitomycin or a nitrosurea). Five half-lives will be required for biologic/targeted therapies with short (\<24 hour) half-lives and pharmacodynamic effects. Patients may have received palliative radiation immediately before (or during) treatment provided radiation does not target the only measurable or evaluable disease.
- Patients must have measurable or evaluable disease
- ECOG performance status \</= 2 (Karnofsky \>/= 60%, Lansky \>/= 50%).
- Patients must have normal organ function defined as: creatinine \</= 1.5 x ULN for children and \</= 2.0 x ULN for adults; total bilirubin \</= 2.0; ALT(SGPT)/AST (SGOT) \</= 5 X ULN. In patients with significant liver disease and chronically elevated liver transaminases, ALT/AST may be elevated as high as 8 X ULN.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days after the last dose.
- Ability to understand and the willingness to sign a written informed consent document.
- Life expectancy of at least 3 months.
- Patients may not be receiving any other experimental agents and/or any other concurrent anticancer agents or therapies except hormonal maintenance.
- Patients must have normal marrow function defined as: absolute neutrophil count \>/= 1,500/mL; platelets \>/= 100,000/mL.
- Patient with neuropathies of CTC grade 1 or less.
- Patients must have normal marrow function defined as: absolute neutrophil count \>/= 1,000/mL; platelets \>/= 75,000/mL.
You may not qualify if:
- Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
- Uncontrolled systemic vascular hypertension (Systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg on medication).
- Patients with clinically significant cardiovascular disease: History of CVA within 6 months Myocardial infarction or unstable angina within 6 months Unstable angina pectoris New York Heart Association Class \> II
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
- Pregnant or lactating women.
- History of hypersensitivity to bevacizumab or murine products, temsirolimus or its metabolites, or any component of the formulation.
- Patients with hemorrhagic brain metastases.
- Patients with prior abdominal surgery within 30 days prior to entering the study.
- Medications with potent inducer or inhibitor of P450 3A4 should be avoided within 5 half lives of temsirolimus.
- Hypersensitivity to carboplatin or any component of the formulation.
- Hypersensitivity to paclitaxel or any component of the formulation.
- History of hypersensitivity to sorafenib or any component of the formulation.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Subbiah V, Westin SN, Wang K, Araujo D, Wang WL, Miller VA, Ross JS, Stephens PJ, Palmer GA, Ali SM. Targeted therapy by combined inhibition of the RAF and mTOR kinases in malignant spindle cell neoplasm harboring the KIAA1549-BRAF fusion protein. J Hematol Oncol. 2014 Jan 14;7:8. doi: 10.1186/1756-8722-7-8.
PMID: 24422672DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Shannon Westin, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 20, 2010
First Posted
August 23, 2010
Study Start
August 19, 2010
Primary Completion
April 30, 2026
Study Completion
April 30, 2026
Last Updated
April 16, 2026
Record last verified: 2026-04