Gemcitabine, Capecitabine, and Bevacizumab in Treating Patients With Metastatic or Unresectable Pancreatic Cancer

Pancreatic Cancer Clinical Trial

Official title:

Multicenter, Open Label, Phase II Clinical Study of Gemcitabine, Capecitabine and Avastin in Pancreatic Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00100815
• Other study ID #: CDR0000409556
• Secondary ID: RPCI-I-19903GENE
• Status: Completed
• Phase: Phase 2
• First received: January 6, 2005
• Last updated: November 19, 2015
• Start date: August 2004

Study information

• Verified date: November 2015
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Biological:
• bevacizumab
30-90 minutes on day 1, every 21 days up to 12 months.

Drug:
• capecitabine
twice daily on days 1-14. Courses repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity.
• gemcitabine hydrochloride
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.

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	Progressive Disease is defined using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000], as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.	every 2-4 months for 1 year and then every 6 months for 5 years	No
Secondary	Percentage of Participants With Grades 3-5 Treatment Related Toxicities	Grade 3, 4 or 5 toxicity rate	Subjects were evaluated for adverse events at each study visit for the duration of their participation in the study, up to 5 years	Yes
Secondary	Percentage of Participants With Improved Quality of Life	Quality of Life was assessed using EORTC QLQ-PAN26. All measures range in score from 1 to 4 as lower scores indicate better outcomes. The improved Quality of Life is defined as a greater than 5% decrease in 2 consecutive scores compared with the baseline score.	assessed at baseline then weekly for 3 weeks	No
Secondary	Clinical Response	Response was evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter; Overall Response (OR) = CR + PR.	Pre-treatment and every 6 weeks from treatment.	No
Secondary	Overall Survival		every 2-4 months for 1 year and then every 6 months for 5 years	No