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Adenocarcinoma of the PancreasPhase 3NCT00088894

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

A Phase 3 study testing gemcitabine hydrochloride, bevacizumab and laboratory biomarker analysis in people with Adenocarcinoma of the Pancreas and Recurrent Pancreatic Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
gemcitabine hydrochloride, bevacizumab and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
590 participants
Where
1 siteUnited States
Study dates
Jun 2004to Jun 2006
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cancer and Leukemia Group B

    Chicago, Illinois, 60606

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine if combination chemotherapy with gemcitabine and bevacizumab achieves superior survival compared to gemcitabine and placebo in patients with previously untreated advanced pancreatic cancer.

SECONDARY OBJECTIVES:

  1. To compare the objective response rates, duration of response, progression free survival, and toxicity of these two regimens in patients with advanced pancreatic cancer.

II. To measure baseline levels of VEGF and correlate with treatment outcome. III. To measure baseline and on treatment levels of additional growth factors that may be co- or counter- regulated with VEGF and correlate with response to treatment.

IV. To measure baseline and on treatment levels of coagulation and endothelial cell activation markers that may predict for thrombotic or bleeding risks related to treatment.

  1. To generate protein expression profiles using a MALDI-TOF based platform from serum samples. To analyze and compare protein expression profiles to elucidate ion peaks that differentiate patients who respond to therapy from patients who do not respond. To identify proteins responsible for the differentially expressed ion peaks. To develop quantitative assays for each of these proteins.

VI. To assess any differences in overall survival within the treatment arm (gemcitabine + bevacizumab), between the two VEGF genotypic groups: Group 1 denoted by individuals with CT or TT genotypes and Group 2 consisting of individuals with CC genotypes.

VII. To conduct an exploratory analysis of gene-toxicity, gene-response, and gene-survival relationships for the various polymorphisms described in the genes implicated in gemcitabine pharmacology (CDA, DCK, DCTD, SLC29A1, SLC28A1, SLC29A2). An exploratory quantitative interaction between the genotypes (group 1 or 2) and the treatment arms (gemcitabine + bevacizumab or gemcitabine + placebo) in predicting overall survival will also be evaluated.

VIII. To identify specific SNPs and genetic variation that are associated with differences among patients in the risk of toxicity.

IX. To compare the effects of gemcitabine + bevacizumab versus gemcitabine + placebo on resource utilization, cost, and utilities, and if applicable, to make estimates of marginal cost-utility.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to ECOG performance status (0-1 vs 2), disease extent (metastatic vs locally advanced), and prior radiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I: 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.

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

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 590 patients (295 per treatment arm) will be accrued for this study within 26.8 months.

Being tested
gemcitabine hydrochloride, bevacizumab, placebo, laboratory biomarker analysis, pharmacogenomic studies
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • gemcitabine hydrochlorideDrug

    Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

    Given IV

  • bevacizumabBiological

    Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

    Given IV

  • placeboOther

    Also called PLCB

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacogenomic studiesOther

    Also called Pharmacogenomic Study

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00088894
Study groupRoleWhat they receive
Arm I (gemcitabine hydrochloride, bevacizumab)ExperimentalPatients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15.
Receives: Drug: gemcitabine hydrochloride; Biological: bevacizumab; Other: laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study
Arm II (gemcitabine hydrochloride, placebo)Active comparatorPatients receive gemcitabine IV as in arm I and placebo IV over 30-90 minutes on days 1 and 15.
Receives: Drug: gemcitabine hydrochloride; Other: placebo; Other: laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival (OS)

    Based on the stratified logrank test.

    Measured: From trial entry until death, assessed up to 7 years

  2. 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.

    Measured: Up to 7 years

  3. 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)

    Measured: Up to 7 years

Secondary outcomes (8)

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

    Measured: Up to 7 years

  2. Duration of response

    Measured: 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

  3. Progression-free survival (PFS)

    The two-way multiplicative Cox model will be used.

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

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

    The two-way multiplicative Cox model will be used.

    Measured: Up to 7 years

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

    Measured: Up to 7 years

  6. Objective response (PR/CR versus stable disease [SD]/progressive disease [PD]) (Clinical endpoint)

    Measured: Up to 7 years

  7. Disease-control (PR/CR/SD versus PD) (Clinical endpoint)

    Measured: Up to 7 years

  8. OS (Clinical endpoint)

    This endpoint will be analyzed in the framework of a 3x6 singly ordered contingency table.

    Measured: Up to 7 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Aug 2004 (estimated)
  2. Study startJun 2004
  3. Primary completionJun 2006

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
590 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00088894
Sponsor's protocol ID
NCI-2012-02960
Other IDs
CALGB-80303, CDR0000377542, U10CA031946
Status last verified
Jun 2013
First submitted
4 Aug 2004
Last updated
5 Jun 2013
Results posted
No

Publications

  • 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.

    PubMed 34616010

  • 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.

    PubMed 34028627

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing gemcitabine hydrochloride, bevacizumab and laboratory biomarker analysis in people with Adenocarcinoma of the Pancreas and Recurrent Pancreatic Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (OS) (time frame: From trial entry until death, assessed up to 7 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00088894, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2013.

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