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

NCT00088894 | Completed Phase 3

• 4 other identifiers: NCI-2012-02960CALGB-80303CDR0000377542U10CA031946
• Study Type: interventional
• Target: 590
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

Outcome Measures

Primary Outcomes (3)

• Overall survival (OS)

  Based on the stratified logrank test.

  From trial entry until death, assessed up to 7 years

• Discrepancies in the response rate between the two genotypic groups (CT/TT or CC) (Pharmacogenetics portion)

  This analysis will be done in the context of a two-way multiplicative logistic model with genotype and treatment as the two factors.

  Up to 7 years

• 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)

  Up to 7 years

Secondary Outcomes (8)

• Objective response (complete or partial [CR/PR])

  Up to 7 years

• Duration of response

  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

• Progression-free survival (PFS)

  From study entry until documented progression of disease or death from any cause, assessed up to 7 years

• Toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0

  Up to 7 years

• Quantitative interaction between the genotypes (group 1 or 2) and the treatment arm (gemcitabine or gemcitabine + bevacizumab) in modeling response (Pharmacogenetics portion)

  Up to 7 years

Study Arms (2)

Arm I (gemcitabine hydrochloride, bevacizumab)

EXPERIMENTAL

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; Biological: bevacizumab; Other: laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study

Arm II (gemcitabine hydrochloride, placebo)

ACTIVE COMPARATOR

Patients receive gemcitabine IV as in arm I and placebo IV over 30-90 minutes on days 1 and 15.

Drug: gemcitabine hydrochloride; Other: placebo; Other: laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study

Interventions

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

Arm I (gemcitabine hydrochloride, bevacizumab); Arm II (gemcitabine hydrochloride, placebo)

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Arm I (gemcitabine hydrochloride, bevacizumab)

placebo OTHER

Given IV

Also known as: PLCB

Arm II (gemcitabine hydrochloride, placebo)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (gemcitabine hydrochloride, bevacizumab); Arm II (gemcitabine hydrochloride, placebo)

pharmacogenomic studies OTHER

Correlative studies

Also known as: Pharmacogenomic Study

Arm I (gemcitabine hydrochloride, bevacizumab); Arm II (gemcitabine hydrochloride, placebo)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I (gemcitabine hydrochloride, bevacizumab); Arm II (gemcitabine hydrochloride, placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Cancer and Leukemia Group B

Chicago, Illinois, 60606, United States

Location

Related Publications (2)

• Quintanilha JCF, Wang J, Sibley AB, Jiang C, Etheridge AS, Shen F, Jiang G, Mulkey F, Patel JN, Hertz DL, Dees EC, McLeod HL, Bertagnolli M, Rugo H, Kindler HL, Kelly WK, Ratain MJ, Kroetz DL, Owzar K, Schneider BP, Lin D, Innocenti F. Bevacizumab-induced hypertension and proteinuria: a genome-wide study of more than 1000 patients. Br J Cancer. 2022 Feb;126(2):265-274. doi: 10.1038/s41416-021-01557-w. Epub 2021 Oct 6.

  PMID: 34616010 DERIVED

• Quintanilha JCF, Liu Y, Etheridge AS, Yazdani A, Kindler HL, Kelly WK, Nixon AB, Innocenti F. Plasma levels of angiopoietin-2, VEGF-A, and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance). Angiogenesis. 2022 Feb;25(1):47-55. doi: 10.1007/s10456-021-09799-1. Epub 2021 May 24.

  PMID: 34028627 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Bevacizumab; Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Hedy Kindler

  Cancer and Leukemia Group B

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2004
• First Posted: August 5, 2004
• Study Start: June 1, 2004
• Primary Completion: June 1, 2006
• Last Updated: June 5, 2013

Record last verified: 2013-06

Locations

US (1)