A Phase I Study of Bendamustine and Bevacizumab for Patients With Advanced Cancers
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 59
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose (MTD) of Bendamustine and Bevacizumab
Study Overview
Brief Summary
The goal of this clinical research study is to find the highest tolerable combination dose of bendamustine and bevacizumab that can be given to patients with advanced cancer. The safety of the drug combination will also be studied.
Detailed Description
The Study Drugs:
Bendamustine is designed to damage DNA (the genetic material) of cancer cells. Bendamustine also interferes with the creation of new DNA, which may keep cancer cells from repairing themselves or forming new cancer cells.
Bevacizumab is designed to block the growth of blood vessels that supply the nutrients needed for tumor growth, which may prevent or slow down the growth of cancer cells. Bevacizumab is no longer FDA approved to treat breast cancer.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of bendamustine based on when you join this study. Up to 4 dose levels of bendamustine will be tested. Up to 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 bendamustine is found.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 13 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients must have histologically confirmed cancer.
- •Patients should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that increases survival by at least 3 months.
- •Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 (capable of all self care but unable to carry out any work activities). Pediatric: performance status Karnovsky (>10) or Lansky (<10).
- •Adequate renal function (serum creatinine </= 2.0 mg/dL or the calculated Glomerular Filtration Rate (GFR) >/= 40 mL/min if creatinine > 2.0 mg/dL). Pediatric: serum creatinine </= 1.5 mg/dL or 2x upper limit of normal, for age.
- •Hepatic function: total bilirubin </= 1.0 mg/dL (Patients with Gilbert's Syndrome must have a total bilirubin </= 3.0 mg/dL); ALT </= 3 times upper limit of normal. If patient has liver metastases, total bilirubin </= 5 mg/dL; ALT </= 5 times upper limit of normal.
- •Adequate bone marrow function (Absolute neutrophil count (ANC) >/= 1,000 cells/uL; Platelets (PLT) >/= 75,000 cells/uL), unless these abnormalities are due to bone marrow involvement.
- •At least three weeks from previous cytotoxic chemotherapy. After targeted or biologic therapy there should be 5 half-lives or 3 weeks, whichever is shorter.
- •All females in childbearing age MUST have a negative urine human chorionic gonadotropin (HCG) test unless prior hysterectomy or menopause (defined as age above 55 and six months without menstrual activity). Patients should not become pregnant or breast-feed while on this study. Sexually active patients should use effective birth control.
- •Must be >/= 13 years of age.
- •Sign informed consent. Pediatric participants: age 13-17 would sign assent, parent or guardian would sign consent.
Exclusion Criteria
- •Pregnant females.
- •Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
- •Serious or non-healing wound, ulcer or bone fracture.
- •Uncontrolled systemic vascular hypertension (systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg).
- •Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection requiring parental antibiotics, or psychiatric illness/social situations that would limit compliance with study requirements.
- •History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
- •Patients with clinical bleeding, active gastric or duodenal ulcer.
- •Patients with history of bleeding central nervous system (CNS) metastasis will be excluded from the trial.
- •Patients with major surgery within 28 days prior to entering the study.
Arms & Interventions
Bendamustine + Bevacizumab
Bendamustine starting dose of 70 mg/m^2 by vein on Days 1 and 2 of a 28 day cycle. Bevacizumab 10 mg/kg by vein on Days 1 & 15 of every 28 day cycle.
Intervention: Bendamustine (Drug)
Bendamustine + Bevacizumab
Bendamustine starting dose of 70 mg/m^2 by vein on Days 1 and 2 of a 28 day cycle. Bevacizumab 10 mg/kg by vein on Days 1 & 15 of every 28 day cycle.
Intervention: Bevacizumab (Drug)
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) of Bendamustine and Bevacizumab
Time Frame: 28 days
MTD defined as highest dose below any dose that has one third or more patients with dose limiting toxicity (DLT). If not more than 33% of the patients in the cohort develop DLT, this cohort considered MTD. DLT defined as any Grade 3 or 4 non-hematologic toxicity as defined in most current version of NCI Common Toxicity Criteria for Adverse Effects (CTCAE).
Secondary Outcomes
No secondary outcomes reported