Capecitabine, Bevacizumab, and Radiation Therapy Followed By Gemcitabine and Bevacizumab in Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed By Surgery

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00114179

Collaborator

NRG Oncology (Other)

Enrollment

Location

Arm

27.9

Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Drugs used in chemotherapy, such as capecitabine and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of pancreatic cancer by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Capecitabine may make tumor cells more sensitive to radiation therapy. Bevacizumab may make tumor cells more sensitive to both chemotherapy and radiation therapy. Giving chemotherapy and bevacizumab before and after radiation therapy may kill more tumor cells. This phase II trial is studying how well giving capecitabine and bevacizumab together with radiation therapy followed by gemcitabine and bevacizumab works in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Pancreas Stage II Pancreatic Cancer Stage III Pancreatic Cancer	Drug: capecitabine Radiation: radiation therapy Biological: bevacizumab Procedure: therapeutic conventional surgery Drug: gemcitabine hydrochloride	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

Compare 1-year overall survival of patients with unresectable locally advanced pancreatic cancer treated with capecitabine, bevacizumab, and radiotherapy followed by maintenance therapy comprising gemcitabine and bevacizumab to a historical control.

SECONDARY OBJECTIVES:

Determine the frequency of serious unacceptable adverse events in patients treated with this regimen.
Determine the response rate in patients treated with this regimen. III. Determine the progression-free survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients with no evidence of disease progression proceed to maintenance therapy. Patients with a marked response may undergo surgery at the discretion of the attending surgeon and then proceed to maintenance therapy approximately 4-8 weeks later.

Maintenance therapy: Beginning within 4-7 weeks after completion of chemoradiotherapy and bevacizumab, patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and bevacizumab IV over 30 minutes on days 1 and 15 provided that blood counts have returned to normal. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for survival.

PROJECTED ACCRUAL: A total of 82 patients will be accrued for this study within 16 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

82 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Bevacizumab With Concurrent Capecitabine and Radiation Followed by Maintenance Gemcitabine and Bevacizumab For Locally Advanced Pancreatic Cancer

Study Start Date :

Jan 1, 2005

Actual Primary Completion Date :

May 1, 2007

Actual Study Completion Date :

May 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (capecitabine, radiation, bevacizumab, gemcitabine) Chemoradiotherapy and bevacizumab: Patients receive oral capecitabine twice daily and undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29. Patients undergo reevaluation 3-4 weeks after completion of chemoradiotherapy and bevacizumab. Patients with no evidence of disease progression proceed to maintenance therapy. Patients with a marked response may undergo surgery at the discretion of the attending surgeon and then proceed to maintenance therapy approximately 4-8 weeks later. Maintenance therapy: Beginning within 4-7 weeks after completion of chemoradiotherapy and bevacizumab, patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and bevacizumab IV over 30 minutes on days 1 and 15 provided that blood counts have returned to normal. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: capecitabine Given orally Other Names: CAPE Ro 09-1978/000 Xeloda Radiation: radiation therapy Undergo radiotherapy Other Names: irradiation radiotherapy therapy, radiation Biological: bevacizumab Given IV Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF Procedure: therapeutic conventional surgery Undergo surgery Drug: gemcitabine hydrochloride Given IV Other Names: dFdC difluorodeoxycytidine hydrochloride gemcitabine Gemzar

Arm

Intervention/Treatment

Experimental: Treatment (capecitabine, radiation, bevacizumab, gemcitabine)

Chemoradiotherapy and bevacizumab: Patients receive oral capecitabine twice daily and undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29. Patients undergo reevaluation 3-4 weeks after completion of chemoradiotherapy and bevacizumab. Patients with no evidence of disease progression proceed to maintenance therapy. Patients with a marked response may undergo surgery at the discretion of the attending surgeon and then proceed to maintenance therapy approximately 4-8 weeks later. Maintenance therapy: Beginning within 4-7 weeks after completion of chemoradiotherapy and bevacizumab, patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and bevacizumab IV over 30 minutes on days 1 and 15 provided that blood counts have returned to normal. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: capecitabine

Given orally

Other Names:

CAPE

Ro 09-1978/000

Xeloda

Radiation: radiation therapy

Undergo radiotherapy

Other Names:

irradiation

radiotherapy

therapy, radiation

Biological: bevacizumab

Given IV

Other Names:

anti-VEGF humanized monoclonal antibody

anti-VEGF monoclonal antibody

Avastin

rhuMAb VEGF

Procedure: therapeutic conventional surgery

Undergo surgery

Drug: gemcitabine hydrochloride

Given IV

Other Names:

dFdC

difluorodeoxycytidine hydrochloride

gemcitabine

Gemzar

Outcome Measures

Primary Outcome Measures

Overall survival rate [1 year]
Will be estimated using the Kaplan-Meier method.

Secondary Outcome Measures

Frequency of patients developing grade 3 or greater adverse events as defined per CTCAE version 3.0 [Up to 1 year]
Progression-free survival [Up to 1 year]
Will be estimated using the Kaplan-Meier method.
Response rate [Up to 1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed adenocarcinoma of the pancreas
Locally advanced disease
Unresectable disease
All malignant disease must be encompassable within a single irradiation field
Radiographically assessable disease
Patients with biliary or gastroduodenal obstruction are eligible provided drainage or surgical bypass was performed prior to initiation of study treatment
No evidence of gastric outlet obstruction
No evidence of duodenal invasion on CT scan
No evidence of metastatic disease in the major viscera
No peritoneal seeding or ascites
Performance status - Zubrod 0-1
Granulocyte count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
No evidence of bleeding diathesis
ALT < 3 times upper limit of normal
Bilirubin < 2.0 mg/dL
INR ≤ 1.5
No evidence of coagulopathy
Creatinine clearance > 50 mL/min
Urine protein < 1,000 mg by 24-hour urine collection (for patients with proteinuria ≥ 1+ by dipstick or urinalysis OR urine protein:creatinine ratio ≥ 1.0)
No myocardial infarction within the past 6 months
No unstable angina within the past 6 months
No arterial thromboembolic events within the past 6 months, including any of the following:
Transient ischemic attack
Cerebrovascular accident
Clinically significant peripheral artery disease
No unstable symptomatic arrhythmia requiring medication (e.g., chronic atrial arrhythmia [i.e., atrial fibrillation or paroxysmal supraventricular tachycardia])
Patients with an atrial arrhythmia are eligible provided the condition is well controlled on stable medication
No New York Heart Association class II-IV congestive heart failure
No history of arteriovenous malformation
No history of aneurysm
No uncontrolled hypertension (i.e., blood pressure > 160/90 mm Hg with medication)
No other clinically significant cardiac disease
No AIDS
No significant infection
No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
Not pregnant
No nursing during and for ≥ 3-4 months after completion of study treatment
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 3-4 months after completion of study treatment
No history of gastrointestinal fistula or perforation
No other malignancy within the past two years except nonmelanoma skin cancer or carcinoma in situ of the cervix, uterus, or bladder
No significant traumatic injury within the past 4 weeks
No serious nonhealing wound or ulcer
No current healing fracture
No known or suspected dihydropyrimidine dehydrogenase deficiency
No other medical condition that would preclude study participation
No concurrent interleukin-11
No prior chemotherapy for pancreatic cancer
More than 2 years since prior chemotherapy for another malignancy
No prior radiotherapy to the planned irradiation field
No concurrent intensity modulated radiotherapy
No other concurrent radiotherapy
See Disease Characteristics
More than 4 weeks since prior major surgical procedure or open biopsy
More than 1 week since prior fine needle aspiration or core biopsy
No prior organ transplantation
No concurrent major surgical procedure
More than 30 days since prior and no concurrent cimetidine
Concurrent ranitidine or a drug from another anti-ulcer class allowed
More than 4 weeks since prior and no concurrent sorivudine or brivudine
No concurrent warfarin during chemoradiotherapy
Concurrent warfarin allowed beginning 2 weeks after completion of chemoradiotherapy
Concurrent low molecular weight heparin allowed (at any time during study participation)
No other concurrent investigational agents
No other concurrent cytotoxic agents