A Phase 1 Study of Bevacizumab in Combination With 1) Sunitinib, 2) Sorafenib, 3) Erlotinib and Cetuximab, 4) Trastuzumab and Lapatinib
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 343
- Locations
- 1
- Primary Endpoint
- Maximum Tolerable Dose (MTD) of Avastin in combination with 4 other study drug/drug combinations
Study Overview
Brief Summary
The goal of this clinical research study is to find the highest tolerable dose of Avastin™ that can be given in combination with 4 other study drug/drug combinations. It will be given with sunitinib, with sorafenib, with a combination of erlotinib and cetuximab, and with a combination of trastuzumab and lapatinib. The safety and effectiveness of these drug combinations will also be studied.
Detailed Description
The Study Drugs:
Bevacizumab (Avastin™) is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels
Sunitinib malate (SutentTM) is designed to block pathways that control important events such as the growth of blood vessels that are vital for the growth of cancer.
Sorafenib (NexavarTM) is designed to block the function of important proteins in cancer cells. These proteins, when active, are in part responsible for the abnormal growth and behavior of cancer cells.
Erlotinib hydrochloride (TarcevaTM) is designed to block the activity of a protein found on the surface of many tumor cells that may control tumor growth and survival. This may stop tumors from growing.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- 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 must be three weeks from prior cytotoxic therapy; if they have recovered their blood counts to eligibility levels sooner and have no mucositis or other acute toxicities, they may be treated earlier but no sooner than two weeks after their last chemotherapy. Patients must be two weeks or five half lives from biologic therapy, whichever is shorter.
- •ECOG performance status </= 2 (Karnofsky >/= 60%).
- •Patients must have normal organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/=75,000/mL; creatinine </= 3 X ULN; total bilirubin </= 2.0; ALT(SGPT) </= 3 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 5 X ULN. Exception for the bevacizumab + erlotinib + cetuximab arm and the bevacizumab + trastuzumab + lapatinib arm: no minimum absolute neutrophil count or platelet count.
- •The effects of bevacizumab on the developing human fetus are unknown. Angiogenesis is of critical importance to fetal development, and bevacizumab is likely to have adverse consequences in terms of fetal development. For this reason, 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 30 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 with a prior DVT/PE are eligible for treatment if they are receiving or have finished receiving appropriate anticoagulation therapy.
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, or unstable angina pectoris.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day
- •Pregnant or lactating women.
- •History of hypersensitivity to bevacizumab, murine products, or any component of the formulation.
- •(For patients on the sunitinib treatment arm and the trastuzumab/lapatinib treatment arm only) Left ventricular ejection fraction of less than 50% unless the patient is receiving an angiotensin-converting enzyme (ACE) inhibitor / angiotensin receptor blocker (ARB) and a beta-blocker.
- •(For sorafenib treatment arm only) Hypersensitivity to sorafenib or any component of the formulation.
- •(For erlotinib and cetuximab treatment arm only) History of hypersensitivity to erlotinib or any component of the formulation.
- •(For erlotinib and cetuximab treatment arm only) History of hypersensitivity to cetuximab, murine products, or any component of the formulation.
- •(For trastuzumab and lapatinib treatment arm only) History of hypersensitivity to trastuzumab, Chinese hamster ovary cell proteins, or any component of the formulation.
- •(For trastuzumab and lapatinib treatment arm only) History of hypersensitivity to lapatinib or any component of the formulation.
- •Patients with clinically significant gastrointestinal bleeding within 28 days prior to entering the study.
- •Patients with hemorrhagic brain metastases.
- •Patients with prior abdominal surgery within 30 days prior to entering the study.
- •(For patients on the sunitinib treatment arm and the trastuzumab/lapatinib treatment arm only) Left ventricular ejection fraction of less than 50%, unless the patient is receiving an angiotensin-converting enzyme (ACE) inhibitor / angiotensin receptor blocker (ARB) and a beta-blocker.
- •(For patients on the sunitinib treatment arm and the trastuzumab/lapatinib treatment arm only) QTc prolongation, defined as greater than 440 milliseconds for males, and greater than 460 milliseconds for females.
Arms & Interventions
Bevacizumab + Sunitinib
Arm 1: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Sunitinib 12.5 mg orally daily for 4 weeks, then 2 weeks off.
Intervention: Bevacizumab (Drug)
Bevacizumab + Sunitinib
Arm 1: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Sunitinib 12.5 mg orally daily for 4 weeks, then 2 weeks off.
Intervention: Sunitinib (Drug)
Bevacizumab + Sorafenib
Arm 2: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Sorafenib 200 mg by mouth daily for 28 Days
Intervention: Bevacizumab (Drug)
Bevacizumab + Sorafenib
Arm 2: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Sorafenib 200 mg by mouth daily for 28 Days
Intervention: Sorafenib (Drug)
Bevacizumab + Erlotinib + Cetuximab
Arm 3: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Erlotinib 50 mg By Mouth Daily for 28 Days + Cetuximab loading dose 100 mg/m² IV and maintenance 75 mg/m² on Days 1, 8, 15, 22.
Intervention: Bevacizumab (Drug)
Bevacizumab + Erlotinib + Cetuximab
Arm 3: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Erlotinib 50 mg By Mouth Daily for 28 Days + Cetuximab loading dose 100 mg/m² IV and maintenance 75 mg/m² on Days 1, 8, 15, 22.
Intervention: Erlotinib (Drug)
Bevacizumab + Erlotinib + Cetuximab
Arm 3: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Erlotinib 50 mg By Mouth Daily for 28 Days + Cetuximab loading dose 100 mg/m² IV and maintenance 75 mg/m² on Days 1, 8, 15, 22.
Intervention: Cetuximab (Drug)
Bevacizumab + Trastuzumab + Lapatinib
Arm 4: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Trastuzumab loading dose 2 mg/kg IV then maintenance dose 1 mg/kg IV on Day 1 + Lapatinib 250 mg By Mouth Daily for 21 Days.
Intervention: Bevacizumab (Drug)
Bevacizumab + Trastuzumab + Lapatinib
Arm 4: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Trastuzumab loading dose 2 mg/kg IV then maintenance dose 1 mg/kg IV on Day 1 + Lapatinib 250 mg By Mouth Daily for 21 Days.
Intervention: Trastuzumab (Drug)
Bevacizumab + Trastuzumab + Lapatinib
Arm 4: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Trastuzumab loading dose 2 mg/kg IV then maintenance dose 1 mg/kg IV on Day 1 + Lapatinib 250 mg By Mouth Daily for 21 Days.
Intervention: Lapatinib (Drug)
Outcomes
Primary Outcomes
Maximum Tolerable Dose (MTD) of Avastin in combination with 4 other study drug/drug combinations
Time Frame: 28 days
MTD defined by Dose Limiting Toxicity in first 28 day cycle (induction phase)
Secondary Outcomes
No secondary outcomes reported