Gemcitabine With or Without Bevacizumab in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00088894
First received: August 4, 2004
Last updated: June 4, 2013
Last verified: June 2013
  Purpose

This randomized phase III trial is studying gemcitabine and bevacizumab to see how well they work compared to gemcitabine alone in treating patients with locally advanced or metastatic pancreatic cancer. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Bevacizumab may also stop the growth of tumor cells by stopping blood flow to the tumor. Combining gemcitabine with bevacizumab may kill more tumor cells. It is not yet known whether gemcitabine is more effective with or without bevacizumab in treating pancreatic cancer.


Condition Intervention Phase
Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage II Pancreatic Cancer
Stage III Pancreatic Cancer
Stage IV Pancreatic Cancer
Drug: gemcitabine hydrochloride
Biological: bevacizumab
Other: placebo
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Phase III Trial Of Gemcitabine Plus Bevacizumab (NSC#704865 IND#7621) Versus Gemcitabine Plus Placebo In Patients With Advanced Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival (OS) [ Time Frame: From trial entry until death, assessed up to 7 years ] [ Designated as safety issue: No ]
    Based on the stratified logrank test.

  • Discrepancies in the response rate between the two genotypic groups (CT/TT or CC) (Pharmacogenetics portion) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    This analysis will be done in the context of a two-way multiplicative logistic model with genotype and treatment as the two factors.

  • Grade 3-4 neutropenia in terms of specific single-nucleotide polymorphisms (SNPs) and/or copy number variations that are associated with the prevalence of these events (Clinical endpoint) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response (complete or partial [CR/PR]) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Time from the first tumor assessment that supports the patient's response to the time of disease progression or death from any cause, assessed up to 7 years ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: From study entry until documented progression of disease or death from any cause, assessed up to 7 years ] [ Designated as safety issue: No ]
    The two-way multiplicative Cox model will be used.

  • Toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 [ Time Frame: Up to 7 years ] [ Designated as safety issue: Yes ]
    The two-way multiplicative Cox model will be used.

  • Quantitative interaction between the genotypes (group 1 or 2) and the treatment arm (gemcitabine or gemcitabine + bevacizumab) in modeling response (Pharmacogenetics portion) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  • Objective response (PR/CR versus stable disease [SD]/progressive disease [PD]) (Clinical endpoint) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  • Disease-control (PR/CR/SD versus PD) (Clinical endpoint) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  • OS (Clinical endpoint) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    This endpoint will be analyzed in the framework of a 3x6 singly ordered contingency table.


Enrollment: 590
Study Start Date: June 2004
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (gemcitabine hydrochloride, bevacizumab)
Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Active Comparator: Arm II (gemcitabine hydrochloride, placebo)
Patients receive gemcitabine IV as in arm I and placebo IV over 30-90 minutes on days 1 and 15.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: placebo
Given IV
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic or cytologic documentation of adenocarcinoma of the pancreas; documentation of disease extent by CT scan is required; radiologically measurable disease is not required; patients with documented invasion of adjacent organs (e.g., duodenum, stomach) by CT scan are not eligible
  • No prior chemotherapy for metastatic disease
  • If the patient received adjuvant therapy, it must have been completed at least 4 weeks prior to enrollment on this study; the patient must have recovered from all treatment related toxicities and must have evidence of disease progression following adjuvant treatment
  • Prior radiation therapy, with or without a radiosensitizing dose of fluoropyrimidines, is allowed provided the patient has disease outside of the radiation port; at least 4 weeks must have elapsed from completion of the radiation therapy and all signs of toxicity must have resolved
  • No prior treatment with gemcitabine or bevacizumab in the adjuvant or metastatic setting
  • No current or recent (within 1 month) use of a thrombolytic agent
  • Patients may not have had prior therapy with other VEGF inhibitors
  • No recent invasive surgical procedures; this includes:

    • Major surgical procedure (e.g. exploratory laparotomy or laparoscopy), open biopsy, or significant traumatic injury within 28 days prior to registration
    • Fine needle aspirations or venous access device within 7 days prior to registration
    • Anticipation of need for major surgical procedures during the course of the study
  • No clinically significant cardiovascular disease; this includes:

    • Uncontrolled hypertension (blood pressure > 150/90 on medication)
    • New York Heart Association grade II or greater congestive heart failure
    • Serious cardiac arrhythmia requiring medication
  • No recent (within 6 months) arterial thrombotic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) are also ineligible
  • No evidence of CNS disease, including primary brain tumor, or any brain metastasis
  • No serious or non-healing wound, ulcer or bone fracture
  • No serious active infection (viral, fungal bacterial); no infection requiring parenteral antibiotics at time of registration
  • Patients with known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies are not eligible
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not to be registered; patients are not considered to have a "currently active" malignancy if they have completed therapy and considered by their physician to be at less than 30% risk of relapse
  • Women must be non-pregnant and non-breast feeding
  • ECOG Performance status of 0, 1 or 2
  • Granulocytes ≥ 1,500/μl
  • Platelet count ≥ 100,000/μl
  • Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 60 mL/min
  • Total bilirubin ≤ 1 x upper limit of normal
  • SGOT(AST) ≤ 2.5 x upper limit of normal
  • PT INR =< 1.5, unless patient is on full dose warfarin
  • Urine protein; for ≥ 1+ proteinuria, 24 hour urine collection must demonstrate < 1 gm of protein/24 hours
  • Required diagnostic procedures:

    • CT of the abdomen
    • Chest x-ray
  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: NCT00088894

Locations
United States, Illinois
Cancer and Leukemia Group B
Chicago, Illinois, United States, 60606
Sponsors and Collaborators
Investigators
Principal Investigator: Hedy Kindler Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00088894     History of Changes
Other Study ID Numbers: NCI-2012-02960, CALGB-80303, CDR0000377542, U10CA031946
Study First Received: August 4, 2004
Last Updated: June 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pancreatic Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Bevacizumab
Gemcitabine
Antibodies
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014