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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00114179
First received: June 13, 2005
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
  • Progression-free survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Will be estimated using the Kaplan-Meier method.

  • Response rate [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 82
Study Start Date: January 2005
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00114179

Locations
United States, Pennsylvania
Radiation Therapy Oncology Group
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
Investigators
Principal Investigator: Christopher Crane Radiation Therapy Oncology Group
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00114179     History of Changes
Other Study ID Numbers: NCI-2012-02661, NCI-2012-02661, CDR0000434846, RTOG-0411, RTOG-0411, U10CA021661
Study First Received: June 13, 2005
Last Updated: December 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Pancreatic Diseases
Antibodies
Antibodies, Monoclonal
Bevacizumab
Capecitabine
Fluorouracil
Gemcitabine
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 23, 2014