Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	CALGB-80303 ECOG-80303, NCT00088894

Special Category: CTSU trial, NCI Web site featured trial

Objectives

Primary

1. Compare survival of patients with locally advanced or metastatic adenocarcinoma of the pancreas treated with gemcitabine with vs without bevacizumab.

Secondary

1. Compare objective response rate, duration of response, and progression-free survival of patients treated with these regimens.
2. Compare the toxicity of these regimens in these patients.
3. Correlate baseline levels of vascular endothelial growth factor (VEGF) with treatment outcome in patients treated with these regimens.
4. Determine baseline and on-treatment levels of additional growth factors that may be co- or counter-regulated with VEGF and correlate these levels with response in patients treated with these regimens.
5. Determine baseline and on-treatment levels of coagulation and endothelial cell activation markers that may predict thrombotic or bleeding risks in patients treated with these regimens.
6. Compare the effects of these regimens on resource utilization, cost, and utilities.
7. Determine estimates of marginal cost-utility.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
  • Locally advanced or metastatic disease
• Not amenable to curative resection
• No invasion of adjacent organs (e.g., duodenum or stomach) by CT scan
• No evidence of CNS disease, including primary brain tumor or brain metastasis

Prior/Concurrent Therapy:

Biologic therapy

• No prior bevacizumab in the adjuvant or metastatic setting
• No other prior vascular endothelial growth factor inhibitors
• No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
• No concurrent pegfilgrastim

Chemotherapy

• See Radiotherapy
• More than 4 weeks since prior adjuvant chemotherapy and recovered
  • Patients must have evidence of disease progression after adjuvant chemotherapy
• No prior chemotherapy for metastatic disease
• No prior gemcitabine in the adjuvant or metastatic setting
• No other concurrent chemotherapy agents

Endocrine therapy

• No concurrent hormones except steroids for adrenal failure, hormones for non-disease-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic

Radiotherapy

• Prior radiotherapy with or without a radiosensitizing dose of fluoropyrimidines allowed provided there is disease outside radiotherapy port
• At least 4 weeks since prior radiotherapy and recovered
• No concurrent palliative radiotherapy

Surgery

• More than 28 days since prior major surgical procedure or open biopsy
• More than 7 days since prior fine needle aspirations
• No concurrent major surgical procedures

Other

• More than 1 month since prior thrombolytic agent
• No concurrent thrombolytic agent
• Concurrent full-dose anticoagulants allowed provided the patient is maintained on a stable dose of warfarin with an in-range INR (between approximately 2-3) OR on a stable dose of low molecular weight heparin

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• No other significant bleeding episodes within the past 6 months

Hepatic

• Bilirubin normal
• SGOT ≤ 2.5 times upper limit of normal (ULN)
• PT and INR ≤ 1.5 times ULN (except for patients on full-dose warfarin)
• No esophageal varices

Renal

• Creatinine ≤ 1.5 mg/dL

  OR

• Creatinine clearance ≥ 60 mL/min
• No proteinuria
  • Patients with ≥ 1+ proteinuria must demonstrate < 1 g/dL of protein on 24-hour urine collection

Cardiovascular

• No clinically significant cardiovascular disease
• No uncontrolled hypertension (i.e., blood pressure > 150/90 mm Hg on medication)
• No arterial thromboembolic event within the past 6 months, including any of the following:
  • Myocardial infarction
  • Unstable angina pectoris
  • Cerebrovascular accident
  • Transient ischemic attack
• No New York Heart Association grade II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No peripheral vascular disease ≥ grade 2
• No clinically significant peripheral artery disease (i.e., claudication on < 1 block)

Pulmonary

• No hemoptysis within the past 6 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 3 months after study participation
• No upper or lower gastrointestinal bleeding within the past 6 months
• No serious or non-healing wound, ulcer, or bone fracture
• No serious active viral, fungal, or bacterial infection
• No infection requiring parenteral antibiotics
• No hypersensitivity to Chinese hamster ovary cell products or other recombinant antibodies
• No significant traumatic injury within the past 28 days
• No other active malignancy except nonmelanoma skin cancer

Expected Enrollment

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

Outcomes

Overall survival

Response
Duration of response
Progression-free survival
Toxicity

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.

Innocenti F, Owzar K, Cox N, et al.: Heritable interleukin-17F (IL17F) gene variation and overall survival (OS) in pancreatic cancer patients (pts): results from a genome-wide association study (GWAS) in CALGB 80303. [Abstract] J Clin Oncol 27 (Suppl 15): A-4531, 2009.

Kindler HL, Niedzwiecki D, Hollis D, et al.: A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): a preliminary analysis of Cancer and Leukemia Group B (CALGB) 80303. [Abstract] American Society of Clinical Oncology 2007 Gastrointestinal Cancers Symposium, 19 -21 January 2007, Orlando, Florida A-108, 2007.

Romanus D, Archer L, Wang X, et al.: Does health-related quality of life (HRQL) improve for patients who respond to chemotherapy? Analysis of patients with advanced pancreas cancer (APC) receiving gemcitabine on Cancer and Leukemia Group B (CALGB) study #80303. [Abstract] J Clin Oncol 25 (Suppl 18): A-9008, 495s, 2007.

Schrag D, Archer L, Wang X, et al.: A patterns-of-care study of post-progression treatment (Rx) among patients (pts) with advanced pancreas cancer (APC) after gemcitabine therapy on Cancer and Leukemia Group B (CALGB) study #80303. [Abstract] J Clin Oncol 25 (Suppl 18): A-4524, 2007.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Hedy Kindler, MD, Protocol chair		Ph: 773-702-0360; 888-824-0200

Related Information

Featured trial article

Registry Information
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
Trial Start Date		2004-06-15
Registered in ClinicalTrials.gov		NCT00088894
Date Submitted to PDQ		2004-06-17
Information Last Verified		2006-04-16
NCI Grant/Contract Number		CA31946

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