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

Study Overview

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

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.

PRIMARY OBJECTIVES: I. 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: I. Determine the frequency of serious unacceptable adverse events in patients treated with this regimen. II. 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. 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. 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.

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

NCI-2012-02661
NCI-2012-02661 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
CDR0000434846
RTOG-0411 (OTHER Identifier) (OTHER: Radiation Therapy Oncology Group)
RTOG-0411 (OTHER Identifier) (OTHER: CTEP)
U10CA021661 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2005-06-13	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-10-29
First Submitted that Met QC Criteria 2005-06-13	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-10-30
First Posted (ACTUAL) 2005-06-14	Results First Posted N/A	Last Verified 2020-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/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. Patient	DRUG: capecitabine Given orally RADIATION: radiation therapy Undergo radiotherapy BIOLOGICAL: bevacizumab Given IV PROCEDURE: therapeutic conventional surgery Undergo surgery DRUG: gemcitabine hydrochloride Given IV

Participant Group/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. Patient

DRUG: capecitabine

Given orally

RADIATION: radiation therapy

Undergo radiotherapy

BIOLOGICAL: bevacizumab

Given IV

PROCEDURE: therapeutic conventional surgery

Undergo surgery

DRUG: gemcitabine hydrochloride

Given IV

Primary Outcome Measures	Measure Description	Time Frame
Overall survival rate	Will be estimated using the Kaplan-Meier method.	1 year

Secondary Outcome Measures	Measure Description	Time Frame
Frequency of patients developing grade 3 or greater adverse events as defined per CTCAE version 3.0		Up to 1 year
Progression-free survival	Will be estimated using the Kaplan-Meier method.	Up to 1 year
Response rate		Up to 1 year

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

NRG Oncology

Investigators

PRINCIPAL_INVESTIGATOR: Christopher Crane, Radiation Therapy Oncology Group

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Crane CH, Winter K, Regine WF, Safran H, Rich TA, Curran W, Wolff RA, Willett CG. Phase II study of bevacizumab with concurrent capecitabine and radiation followed by maintenance gemcitabine and bevacizumab for locally advanced pancreatic cancer: Radiation Therapy Oncology Group RTOG 0411. J Clin Oncol. 2009 Sep 1;27(25):4096-102. doi: 10.1200/JCO.2009.21.8529. Epub 2009 Jul 27.

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