5-Fluorouracil, Bevacizumab, and Radiation Followed by Modified FOLFOX6 and Bevacizumab in Stage II/III Rectal Cancer

This study has been completed.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00308516
First received: March 28, 2006
Last updated: May 14, 2013
Last verified: May 2013
  Purpose

This phase II trial will investigate the combination of adjuvant 5-fluorouracil, radiation, and bevacizumab in patients with stage II and III rectal cancer, followed by FOLFOX6 and bevacizumab. Fluorouracil (FU) has proven to be an effective and safe regimen in the treatment of stage II and III rectal cancer. Recent evidence has proven fluorouracil/leucovorin (FL) in combination with bevacizumab is superior to FL alone and when combined with irinotecan is superior to (irinotecan plus fluorouracil/leucovorin (IFL) alone. This trial will be one of the first clinical trials to evaluate a combination of targeted therapy, radiation, and chemotherapy in the adjuvant treatment of a common solid tumor.


Condition Intervention Phase
Rectal Cancer
Cancer of the Rectum
Colorectal Cancer
Drug: 5-Fluorouracil
Drug: Bevacizumab
Procedure: Radiation Therapy
Drug: Oxaliplatin
Drug: Leucovorin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of 5-Fluorouracil, Bevacizumab (Avastin), and Radiation in the Preoperative or Adjuvant Treatment of Patients With Stage II / III Rectal Cancer

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment


Secondary Outcome Measures:
  • Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Length of time, in months, that patients were alive from their first date of protocol treatment until death.


Enrollment: 66
Study Start Date: March 2006
Study Completion Date: February 2012
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A - Preoperative

Each patient enrolled in the preoperative cohort received 5-fluorouracil (5-FU) 225 mg/m2 as a continuous infusion (IVCI) on days 1-42 through a portable infusion pump and central venous catheter. Bevacizumab 5 mg/kg was administered intravenously (IV) on days 1 and 15. Additionally these patients received radiation therapy to 50.4 Gy (1.8 Gy/day or 28 fractions) Monday through Friday during weeks 1-6.

At least 8 weeks after surgery, patients in cohort A began 4 months of chemotherapy and bevacizumab. This adjuvant treatment consisted of 5-FU 400 mg/m2 IV bolus over 2-4 minutes followed by 2400 mg/m2 IVCI over 46 hours, leucovorin 350 mg as a 2-hour infusion, oxaliplatin 85 mg/m2 IV (modified FOLFOX6) and bevacizumab 5 mg/kg IV all on days 1 and 15 of each cycle.

Drug: 5-Fluorouracil

Combined Modality Treatment:

fluorouracil 225mg/m2 IV continuous infusion days 1-42

Systemic Treatment:

5-fluorouracil 400 mg/m2 bolus 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15

Other Names:
  • Fluorouracil
  • Efudex
  • 5-FU
Drug: Bevacizumab

Combined Modality Treatment:

bevacizumab 5mg/kg IV infusion days 1, 15, and 29

Systemic Treatment:

bevacizumab 5 mg/kg days 1 and 15

Other Name: Avastin
Procedure: Radiation Therapy
radiation 1.8 Gy/day or 28 fractions weeks 1-6
Drug: Oxaliplatin

Systemic Treatment:

oxaliplatin 85 mg/m2 days 1 and 15

Other Name: Eloxatin
Drug: Leucovorin

Systemic Treatment:

leucovorin 350 mg prior to FU on days 1 and 15

Other Name: Folinic acid
Experimental: Cohort B - Combined Modality

All patients enrolled in cohort B received 5-fluorouracil (5-FU) 225 mg/m2 IVCI on days 1-42. Bevacizumab was administered at 5 mg/kg IV on day 1 every 2 weeks. These patients also received radiation to 50.4 Gy (1.8 Gy/day or 28 fractions)Monday through Friday during weeks 1-6.

Six weeks after the completion of adjuvant 5-FU/radiation, patients began treatment with 5-FU 400 mg/m2 IV bolus over 2-4 minutes followed by 2400 mg/m2 IVCI over 46 hours, leucovorin 350 mg as a 2-hour infusion, oxaliplatin 85 mg/m2 IV (modified FOLFOX6) and bevacizumab 5 mg/kg IV all on days 1 and 15 of each cycle.

Drug: 5-Fluorouracil

Combined Modality Treatment:

fluorouracil 225mg/m2 IV continuous infusion days 1-42

Systemic Treatment:

5-fluorouracil 400 mg/m2 bolus 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15

Other Names:
  • Fluorouracil
  • Efudex
  • 5-FU
Drug: Bevacizumab

Combined Modality Treatment:

bevacizumab 5mg/kg IV infusion days 1, 15, and 29

Systemic Treatment:

bevacizumab 5 mg/kg days 1 and 15

Other Name: Avastin
Procedure: Radiation Therapy
radiation 1.8 Gy/day or 28 fractions weeks 1-6
Drug: Oxaliplatin

Systemic Treatment:

oxaliplatin 85 mg/m2 days 1 and 15

Other Name: Eloxatin
Drug: Leucovorin

Systemic Treatment:

leucovorin 350 mg prior to FU on days 1 and 15

Other Name: Folinic acid

Detailed Description:

All eligible patients will receive combined modality treatment initially. Systemic treatment will begin 4-6 weeks after completion of the Combined Modality portion and will complete 4 cycles of a 4 week regimen. Patients with no evidence of disease following systemic therapy may continue single agent bevacizumab for up to one year. After all treatment is completed, patients will be re-evaluated with imaging to establish a new baseline. Patients will be re-evaluated thereafter for up to a total of 5 years.

Combined Modality Treatment:

  • bevacizumab 5mg/kg IV infusion days 1, 15, and 29
  • fluorouracil 225mg/m2 IV continuous infusion days 1-42
  • radiation 1.8 Gy/day or 28 fractions weeks 1-6

Systemic Treatment:

  • 5-fluorouracil 400 mg/m2 bolus
  • 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15
  • leucovorin 350 mg prior to FU on days 1 and 15
  • oxaliplatin 85 mg/m2 days 1 and 15
  • bevacizumab 5 mg/kg days 1 and 15
  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed Stage I or II rectal cancer
  • Patients must be candidates for preoperative or adjuvant chemoradiation.
  • Patients enrolling in the adjuvant chemoradiation cohort must have undergone surgical resection of the primary rectal tumor between 28 and 56 days (i.e., 4-8 weeks) prior to study treatment.
  • ECOG performance status 0-1
  • Adequate bone marrow, liver, and kidney function
  • At least 18 years of age
  • Able to give written informed consent

Exclusion Criteria:

  • Treatment with prior chemotherapy or radiation for rectal cancer
  • History of myocardial infarction
  • Uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication or peripheral vascular disease
  • History of stroke within 6 months
  • History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess within 6 months
  • Symptomatic sensory or peripheral neuropathy
  • Prior treatment with anti-angiogenic agents
  • Prior malignancy in the past 5 years
  • Active infections or serious underlying medical condition
  • Major surgery less than 28 days prior
  • Women who are pregnant or lactating
  • Thrombolytic therapy within 10 days of starting bevacizumab
  • PEG tube, G-tube, or external biliary stents
  • Proteinuria
  • Non healing wound, ulcer or fracture
  • History of bleeding diathesis or coagulopathy
  • Hemoptysis
  • Participation in another experimental trial within 28 days
  • Uncontrolled anticoagulant therapy
  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: NCT00308516

Locations
United States, Alabama
Northeast Alabama Regional Medical Center
Anniston, Alabama, United States, 36207
United States, Arkansas
Northeast Arkansas Clinic
Jonesboro, Arkansas, United States, 72401
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
Integrated Community Oncology Network
Jacksonville, Florida, United States, 32256
Watson Clinic Center for Cancer Care and Research
Lakeland, Florida, United States, 33805
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
Wellstar Cancer Research
Marietta, Georgia, United States, 30060
United States, Kentucky
Consultants in Blood Disorders and Cancer
Louisville, Kentucky, United States, 40207
United States, Pennsylvania
Consultants in Medical Oncology and Hematology
Drexel Hill, Pennsylvania, United States, 19026
United States, South Carolina
Spartanburg Regional Medical Center
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology
Nashville, Tennessee, United States, 37205
United States, Texas
South Texas Oncology and Hematology
San Antonio, Texas, United States, 78258
United States, Virginia
Peninsula Cancer Institute
Newport News, Virginia, United States, 23601
Sponsors and Collaborators
SCRI Development Innovations, LLC
Genentech, Inc.
Investigators
Principal Investigator: David R. Spigel, MD SCRI Development Innovations, LLC
  More Information

Publications:
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00308516     History of Changes
Other Study ID Numbers: SCRI GI 65, AVF3105s
Study First Received: March 28, 2006
Results First Received: March 26, 2013
Last Updated: May 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Rectal Cancer
Cancer of the Rectum
Colorectal Cancer
Bevacizumab

Additional relevant MeSH terms:
Colorectal Neoplasms
Rectal Neoplasms
Digestive System Neoplasms
Gastrointestinal Neoplasms
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Bevacizumab
Colonic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014