Clinical trial NCT00100815: Gemcitabine, Capecitabine, and Bevacizumab in Treating Patients With Metastatic or Unresectable Pancreatic Cancer
Official title: Multicenter, Open Label, Phase II Clinical Study of Gemcitabine, Capecitabine and Avastin in Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: adenocarcinoma of the pancreas
recurrent pancreatic cancer
stage IV pancreatic cancer
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
First posted: 2005-01-07
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab may stop the growth of tumor cells by stopping blood flow to the tumor. Giving gemcitabine and capecitabine together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gemcitabine and capecitabine together with bevacizumab works in treating patients with metastatic or unresectable pancreatic cancer.

Detailed description: OBJECTIVES:

Primary

* Determine progression-free survival of patients with metastatic or unresectable adenocarcinoma of the pancreas treated with gemcitabine, capecitabine, and bevacizumab.

Secondary

* Determine clinical response in patients treated with this regimen.
* Determine toxicity of this regimen in these patients.
* Determine quality of life of patients treated with this regimen.

OUTLINE: This is an open-label, multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1, oral capecitabine twice daily on days 1-14, and gemcitabine IV over 30 minutes on days 1 and 8. Courses repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline then weekly for 3 weeks.

Patients are followed every 2-4 months for 1 year and then every 6 months for at least 5 years.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study within 8.8-17.5 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed adenocarcinoma of the pancreas meeting 1 of the following criteria:

  * Newly diagnosed or previously treated metastatic disease
  * Unresectable disease
* No CNS or brain metastases

PATIENT CHARACTERISTICS:

Age

* Over 18

Performance status

* ECOG 0-1

Life expectancy

* More than 3 months

Hematopoietic

* Absolute neutrophil count \> 1,500/mm\^3
* WBC \> 3,000/mm\^3
* Platelet count \> 100,000/mm\^3
* Hemoglobin ≥ 9 g/dL (transfusion or epoetin alfa allowed)
* No evidence of bleeding diathesis or coagulopathy

Hepatic

* Bilirubin \< 2 mg/dL
* AST or ALT \< 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
* INR \< 1.5 (except for patients receiving full-dose warfarin)

Renal

* Creatinine \< 1.5 mg/dL
* No proteinuria OR
* Urine protein \< 500 mg by 24-hour urine collection
* No clinically significant impairment of renal function

Cardiovascular

* No uncontrolled hypertension (blood pressure \> 160/110 mm Hg on medication)
* No New York Heart Association class II-IV congestive heart failure
* No unstable symptomatic arrhythmia requiring medication

  * Chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) allowed
* No clinically significant grade II-IV peripheral vascular disease
* No arterial thromboembolic event within the past 6 months, including any of the following:

  * Transient ischemic attack
  * Cerebrovascular accident
  * Unstable angina
  * Myocardial infarction

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other serious systemic disease
* No significant traumatic injury within the past 28 days
* No serious non-healing wound, ulcer, or bone fracture
* No history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* More than 28 days since prior major surgery or open biopsy
* More than 7 days since prior fine needle aspirations or core biopsies
* No concurrent major surgery

Other

* More than 4 weeks since prior and no concurrent participation in any other experimental drug study
* More than 12 months since prior adjuvant therapy
* No prior systemic therapy for metastatic disease

Primary outcomes:
measure: Progression-free Survival
timeFrame: every 2-4 months for 1 year and then every 6 months for 5 years
Secondary outcomes:
measure: Percentage of Participants With Grades 3-5 Treatment Related Toxicities
timeFrame: Subjects were evaluated for adverse events at each study visit for the duration of their participation in the study, up to 5 years
measure: Percentage of Participants With Improved Quality of Life
timeFrame: assessed at baseline then weekly for 3 weeks
measure: Clinical Response
timeFrame: Pre-treatment and every 6 weeks from treatment.
measure: Overall Survival
timeFrame: every 2-4 months for 1 year and then every 6 months for 5 years
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Roswell Park Cancer Institute
name: Renuka Iyer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Javle M, Yu J, Garrett C, Pande A, Kuvshinoff B, Litwin A, Phelan J 3rd, Gibbs J, Iyer R. Bevacizumab combined with gemcitabine and capecitabine for advanced pancreatic cancer: a phase II study. Br J Cancer. 2009 Jun 16;100(12):1842-5. doi: 10.1038/sj.bjc.6605099. Epub 2009 Jun 2.