Nab-paclitaxel, Gemcitabine, and Bevacizumab in Advanced Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01113476
First received: April 28, 2010
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Advanced Cancer
Drug: Nab-paclitaxel
Drug: Bevacizumab
Drug: Gemcitabine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Combination of Nab-paclitaxel, Gemcitabine, and Bevacizumab in Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Gemcitabine, Nab-Paclitaxel and Bevacizumab [ Time Frame: With each 28 day cycle ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • Response Rate [ Time Frame: After 2, 28 day cycles ] [ Designated as safety issue: No ]
    Patients with lymphoma measured per WHO criteria, all others evaluated with RECIST (version 1.1) criteria. Measurable disease defined as at least one lesion that can be accurately measured in at least one dimension. Best Response: Measurement of longest dimension of each lesion size is required for follow-up. Complete Response (CR): Disappearance of all target and non-target lesions and no evidence of new lesions documented by 2 disease assessments at least 4 weeks apart. Partial Response (PR): At least 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions, taking as reference baseline sum of LD. Stable Disease (SD): Stable disease defined as any condition not meeting above criteria. Progressive Disease (PD): At least a 20% increase in sum of LD of target lesions taking as reference smallest sum LD or appearance of new lesions after study entry.


Estimated Enrollment: 120
Study Start Date: April 2010
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: Nab-paclitaxel
Starting dose of 50 mg/m^2 on Day 1, 8 + 15 every 28 days (+/- 2 days)
Other Names:
  • paclitaxel
  • Abraxene
  • ABI-007
Drug: Bevacizumab
Starting dose of 5 mg/m^2 on Day 1 + 15 every 28 days (+/- 2 days)
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Gemcitabine
1000 mg/kg Day 1, 8 + 15 every 28 days (+/- 2 days)
Other Names:
  • Gemcitabine Hydrochloride
  • Gemzar

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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.
  3. ECOG performance status </= 2 (Karnofsky >/= 60%).
  4. 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.
  5. 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.
  6. Ability to understand and the willingness to sign a written informed consent document.
  7. Patients may not be receiving any other investigational agents and/or any other concurrent anticancer agents or therapies.

Exclusion Criteria:

  1. Patients with hemoptysis within 28 days prior to entering the study.
  2. Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
  3. Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140mmHg, diastolic blood pressure > 90 mmHg on medication).
  4. Pregnant or lactating women.
  5. History of hypersensitivity to bevacizumab, murine products, or any component of the formulation.
  6. History of hypersensitivity to gemcitabine
  7. History of hypersensitivity to nab-paclitaxel or paclitaxel
  8. Patients with clinically significant cardiovascular disease: Myocardial Infarction or unstable angina pectoris within the last 6 months, Class III/IV NYHA heart failure
  9. History of CVA within 6 months
  10. History of surgery within last 28 days.
  11. Grade 3/4 proteinuria
  12. Nephrotic syndrome
  13. Incompletely healed wound.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01113476

Contacts
Contact: David S. Hong, MD 713-794-1226

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: David S. Hong, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: David S. Hong, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01113476     History of Changes
Other Study ID Numbers: 2009-0855, NCI-2011-02061
Study First Received: April 28, 2010
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Advanced Malignancies
Nab-paclitaxel
Gemcitabine
Bevacizumab

Additional relevant MeSH terms:
Neoplasms
Antibodies, Monoclonal
Gemcitabine
Bevacizumab
Paclitaxel
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on September 14, 2014