Phase I Study of Combination of Nab-paclitaxel, Gemcitabine, and Bevacizumab in Advanced Malignancies
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 176
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose (MTD) of Gemcitabine, Nab-Paclitaxel and Bevacizumab
Study Overview
Brief Summary
The goal of this clinical research study is to find the highest tolerable dose of the combination of Abraxane (nab-paclitaxel), Gemzar (gemcitabine), and Avastin (bevacizumab) that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.
Detailed Description
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of a combination of nab-paclitaxel, gemcitabine, and bevacizumab based on when you joined this study. All participants will receive the same dose level of gemcitabine. However, the first group of participants will receive the lowest dose level of nab-paclitaxel and bevacizumab. Each new group will receive a higher dose for one of the drugs than the group before it, if no intolerable side effects were seen. The other drug may be at the same dose or a lower dose. This will continue until the highest tolerable dose of combination of nab-paclitaxel, gemcitabine, and bevacizumab is found. Up to 15 dose levels of the study drug combination will be tested. Three (3) to 4 participants will be enrolled at each dose level.
Once the highest tolerated dose is found, up to 10 more participants will be added at that dose level. This is called an expansion group.
Study Drug Administration:
On Days 1, 8, and 15 of each 28-day cycle, you will receive nab-paclitaxel and gemcitabine by vein over about 90 minutes total. Also, if the first dose is well tolerated, you may be given the remaining doses of nab-paclitaxel and gemcitabine at home.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- 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; 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 > 140mmHg, diastolic blood pressure > 90 mmHg on medication).
- •Pregnant or lactating women.
- •History of hypersensitivity to bevacizumab, murine products, or any component of the formulation.
- •History of hypersensitivity to gemcitabine.
- •History of hypersensitivity to nab-paclitaxel or paclitaxel.
- •Patients with clinically significant cardiovascular disease: Myocardial Infarction or unstable angina pectoris within the last 6 months, Class III/IV NYHA heart failure.
- •History of CVA within 6 months.
- •History of surgery within last 28 days.
- •Grade 3/4 proteinuria.
- •Nephrotic syndrome.
- •Incompletely healed wound.
Arms & Interventions
Nab-paclitaxel, Gemcitabine + Bevacizumab
Starting doses of Nab-paclitaxel 50 mg/m^2, Bevacizumab 5 mg/kg + fixed dose of Gemcitabine 1000 mg/m^2
Intervention: Nab-paclitaxel (Drug)
Nab-paclitaxel, Gemcitabine + Bevacizumab
Starting doses of Nab-paclitaxel 50 mg/m^2, Bevacizumab 5 mg/kg + fixed dose of Gemcitabine 1000 mg/m^2
Intervention: Bevacizumab (Drug)
Nab-paclitaxel, Gemcitabine + Bevacizumab
Starting doses of Nab-paclitaxel 50 mg/m^2, Bevacizumab 5 mg/kg + fixed dose of Gemcitabine 1000 mg/m^2
Intervention: Gemcitabine (Drug)
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) of Gemcitabine, Nab-Paclitaxel and Bevacizumab
Time Frame: With each 28 day cycle
A MTD is defined as the dose level below the dose at which 2 of 6 patients experience drug-related dose limiting toxicity (DLT) in the first cycle. DLT defined as any grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v4.0, even if expected and believed related to study medications (except nausea and vomiting responsive to appropriate regimens or alopecia), any Grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by the NCI-CTCAE), despite supportive care; any Grade 4 nausea or vomiting \> 5 days despite maximum anti-nausea regimens, and any other Grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-CTCAE v.4.0 that is attributable to therapy.
Secondary Outcomes
- Response Rate(After 2, 28 day cycles)