A Phase I Trial of Bevacizumab and Temsirolimus in Patients With Advanced Malignancy
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 193
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose (MTD)
Study Overview
Brief Summary
The goal of this clinical research study is to find the highest tolerable dose of Avastin (bevacizumab) and Torisel (temsirolimus) that can be given, in combination, to patients with advanced cancer that has spread or is unable to be surgically removed. The safety of this drug combination will also be studied.
Detailed Description
The Study Drugs:
Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels that supply nutrients necessary for tumor growth.
Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells to die.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of bevacizumab and temsirolimus combined, based on when you joined this study. Up to 13 dose levels of the study drug combination will be tested. Three (3) participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the study drug combination is found.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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 should be at least four weeks from the last day of therapeutic radiation or cytotoxic chemotherapy or from antibody therapy, or at least five half-lives from non-cytotoxic targeted or biologic therapy. Patients may have received palliative radiation immediately before (or during) treatment provided radiation is not to the only target lesion available.
- •ECOG performance status </= 2 (Karnofsky >/= 60%).
- •Patients must have allowable organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/=50,000/mL; creatinine </= 3 X ULN; total bilirubin </= 3.0; AST(SGOT)/ALT(SGPT) </= 5 X ULN; fasting level of total cholesterol of no more than 350mg/dL; triglyceride level of no more than 400mg/dL.
- •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
- •Patients may not be receiving any other investigational agents and/or any other concurrent anticancer agents or therapies.
Exclusion Criteria
- •Patients with hemoptysis within 28 days prior to entering the study.
- •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
- •Pregnant or lactating women.
- •History of hypersensitivity to bevacizumab, murine products, or any component of the formulation.
- •History of hypersensitivity to Temsirolimus or its metabolites (including sirolimus), polysorbate 80, or to any component of the formulation
- •Patients that are taking CYP3A4 inducers and/or inhibitors. Please see section 3.2 in the protocol for details. If a patient has a history of taking CYP3A4 inducers and/or inhibitors prior to enrollment on the protocol, it is strongly recommended that the patient stops the drug and waits at least 5 half-lives of said drug before initiating therapy on protocol.
Arms & Interventions
Bevacizumab + Temsirolimus
Bevacizumab 5 mg/kg By Vein Over 90 Minutes on Day 1 of Each 21 Day Cycle. Temsirolimus 5 mg By Vein Over 30-60 Minutes on Days 1, 8, 15 of Each 21 Day Cycle. First tumor biopsy during screening visit and Second at the end of Cycle 1. DCE-MRI (dynamic contrast-enhanced magnetic resonance imaging) scan during screening visit, at 24-48 hours after the start of Cycle 1, and at the end of Cycle 1.
Intervention: Bevacizumab (Drug)
Bevacizumab + Temsirolimus
Bevacizumab 5 mg/kg By Vein Over 90 Minutes on Day 1 of Each 21 Day Cycle. Temsirolimus 5 mg By Vein Over 30-60 Minutes on Days 1, 8, 15 of Each 21 Day Cycle. First tumor biopsy during screening visit and Second at the end of Cycle 1. DCE-MRI (dynamic contrast-enhanced magnetic resonance imaging) scan during screening visit, at 24-48 hours after the start of Cycle 1, and at the end of Cycle 1.
Intervention: Temsirolimus (Drug)
Bevacizumab + Temsirolimus
Bevacizumab 5 mg/kg By Vein Over 90 Minutes on Day 1 of Each 21 Day Cycle. Temsirolimus 5 mg By Vein Over 30-60 Minutes on Days 1, 8, 15 of Each 21 Day Cycle. First tumor biopsy during screening visit and Second at the end of Cycle 1. DCE-MRI (dynamic contrast-enhanced magnetic resonance imaging) scan during screening visit, at 24-48 hours after the start of Cycle 1, and at the end of Cycle 1.
Intervention: Additional Blood Drawn (Procedure)
Bevacizumab + Temsirolimus
Bevacizumab 5 mg/kg By Vein Over 90 Minutes on Day 1 of Each 21 Day Cycle. Temsirolimus 5 mg By Vein Over 30-60 Minutes on Days 1, 8, 15 of Each 21 Day Cycle. First tumor biopsy during screening visit and Second at the end of Cycle 1. DCE-MRI (dynamic contrast-enhanced magnetic resonance imaging) scan during screening visit, at 24-48 hours after the start of Cycle 1, and at the end of Cycle 1.
Intervention: Biopsy (Procedure)
Bevacizumab + Temsirolimus
Bevacizumab 5 mg/kg By Vein Over 90 Minutes on Day 1 of Each 21 Day Cycle. Temsirolimus 5 mg By Vein Over 30-60 Minutes on Days 1, 8, 15 of Each 21 Day Cycle. First tumor biopsy during screening visit and Second at the end of Cycle 1. DCE-MRI (dynamic contrast-enhanced magnetic resonance imaging) scan during screening visit, at 24-48 hours after the start of Cycle 1, and at the end of Cycle 1.
Intervention: DCE-MRI Scan (Procedure)
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD)
Time Frame: 21 days
Maximum tolerated dose defined as the dose level below the dose at which two of six patients experience drug-related dose limiting toxicity in the first cycle.
Secondary Outcomes
- Anti-Tumor Efficacy(Baseline, 24-48 hours after the start of Cycle 1, and at the end of Cycle 1. Cycles are 21 days.)