A Phase I Trial of Bevacizumab and Bortezomib in Patients With Advanced Malignancy
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 104
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose (MTD) and Dose-limiting toxicities (DLT) of Combination Treatment with Bevacizumab and Bortezomib
Study Overview
Brief Summary
The goal of this clinical research study is to find the highest tolerable dose of Avastin™ (bevacizumab) and Velcade™ (bortezomib) that can be given in combination to patients with a metastatic or unresectable advanced malignancy. The safety and effectiveness of this drug combination will also be studied.
Detailed Description
Bevacizumab is an anti-cancer drug designed to prevent or slow down the growth of cancer cells by blocking blood vessels that supply nutrients necessary for tumor growth.
Bortezomib is an anti-cancer drug designed to block the proteins needed for tumor growth. This may cause cancer cells to die.
If you are found to be eligible to take part in this study, you will be enrolled into a group of about 6 participants. The first group of participants will receive the lowest dose of bevacizumab and bortezomib combined. The next group of participants will receive the next highest dose of bevacizumab and bortezomib combined. This process will continue until the study doctor finds the highest dose that can be tolerated. The dose that you receive will depend on when you are enrolled in this study and the safety data that is available at that time. The dose of bevacizumab and bortezomib that you receive may be lowered if you do not tolerate the study drug combination well. You will not receive any doses of the study drug higher than the dose you are first assigned to.
Bevacizumab and bortezomib will be given in "cycles." Cycles will be about 21 days long or longer, depending on any side effects you may experience. During Cycle 1, Day 1, you will receive bevacizumab by vein over 90 minutes. If bevacizumab is well tolerated in Cycle 1, it will given over 60 minutes in Cycle 2. If it is well tolerated in Cycle 2, it will be given over 30 minutes in Cycle 3. It will continue to be given over 30 minutes in further cycles as long as the drug is still being well tolerated. Depending on which dose level you are assigned to, you will receive bortezomib on Days 1 and 8, or on Days 1, 4, 8, and 11. You will receive bortezomib by vein over about 1-5 minutes.
You will have blood drawn (about 1 tablespoon each time) for routine tests once a week during Cycle 1. You will have a physical exam sometime between Days 7 to 14 during Cycle 1. During the rest of the cycles, you will have a physical exam and blood drawn (about 1 tablespoon each time) for routine tests once every 3 weeks. The status of the disease will be measured by a CT or MRI scan after every 2 cycles.
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 complete response (CR) rate of at least 10% or improves survival by at least three months.
- •Patients must be >/= 6 weeks beyond treatment with nitrosoureas or mitomycin-C, >/= 4 weeks beyond other chemo- or radiotherapy, and must have recovered to </= grade 1 toxicity for any treatment-limiting toxicity of prior therapy. (Exception: patients who received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, ribs, sternum, scapulae, vertebrae or skull were not included in the radiotherapy field). Patients who have received non-chemotherapeutic biologic agents must wait 5 half-lives or 4 weeks, whichever is shorter, from the last day of treatment.
- •The Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/= 60%).
- •Patients must have normal organ and marrow function defined as: leukocytes >/= 3,000/mL; absolute neutrophil count >/= 1,500/mL; platelets >/=75,000/mL; creatinine </= 2 * Upper Limits of Normal (ULN); total bilirubin </= 2.0; alanine aminotransferase (ALT or SGPT) </= 3 * ULN; Exception for patients with liver metastasis: total bilirubin </= 3 * ULN; ALT(SGPT) </= 5 * ULN.
- •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.
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.
- •Patients with clinically significant cardiovascular disease, including: history of cerebrovascular accident (CVA) within 6 months, myocardial infarction or unstable angina within 6 months, 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.
- •History of hypersensitivity to bortezomib, boron, mannitol, or any component of the formulation.
- •(Only for the 10-patient expansion cohort after identification of the MTD): Patients must be willing to undergo biopsy before treatment and at the end of cycle 1.
Arms & Interventions
Bevacizumab + Bortezomib
Bevacizumab starting Dose 2.5 mg/kg By Vein On Day 1 Every 21 Days. Bortezomib starting Dose 0.7 mg/m^2 By Vein On Days 1 and 8 Every 21 Days.
Intervention: Bevacizumab (Drug)
Bevacizumab + Bortezomib
Bevacizumab starting Dose 2.5 mg/kg By Vein On Day 1 Every 21 Days. Bortezomib starting Dose 0.7 mg/m^2 By Vein On Days 1 and 8 Every 21 Days.
Intervention: Bortezomib (Drug)
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD) and Dose-limiting toxicities (DLT) of Combination Treatment with Bevacizumab and Bortezomib
Time Frame: Weekly during 21 Day Cycle
The MTD is defined as the highest dose studied in which the incidence of DLT was less than 33%.
Secondary Outcomes
No secondary outcomes reported