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

Primary Purpose

Rectal Cancer, Cancer of the Rectum, Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
5-Fluorouracil
Bevacizumab
Radiation Therapy
Oxaliplatin
Leucovorin
Sponsored by
SCRI Development Innovations, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring Rectal Cancer, Cancer of the Rectum, Colorectal Cancer, Bevacizumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Northeast Alabama Regional Medical Center
  • Northeast Arkansas Clinic
  • Florida Cancer Specialists
  • Integrated Community Oncology Network
  • Watson Clinic Center for Cancer Care and Research
  • Northeast Georgia Medical Center
  • Wellstar Cancer Research
  • Consultants in Blood Disorders and Cancer
  • Consultants in Medical Oncology and Hematology
  • Spartanburg Regional Medical Center
  • Chattanooga Oncology Hematology Associates
  • Tennessee Oncology
  • South Texas Oncology and Hematology
  • Peninsula Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort A - Preoperative

Cohort B - Combined Modality

Arm Description

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.

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.

Outcomes

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
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
Overall Survival (OS) is defined ad the Length of time, in months, that patients were alive from their first date of protocol treatment until death.

Full Information

First Posted
March 28, 2006
Last Updated
November 11, 2021
Sponsor
SCRI Development Innovations, LLC
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00308516
Brief Title
5-Fluorouracil, Bevacizumab, and Radiation Followed by Modified FOLFOX6 and Bevacizumab in Stage II/III Rectal Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
March 2006 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SCRI Development Innovations, LLC
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer, Cancer of the Rectum, Colorectal Cancer
Keywords
Rectal Cancer, Cancer of the Rectum, Colorectal Cancer, Bevacizumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
66 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort A - Preoperative
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort B - Combined Modality
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
5-Fluorouracil
Other Intervention Name(s)
Fluorouracil, Efudex, 5-FU
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Combined Modality Treatment: bevacizumab 5mg/kg IV infusion days 1, 15, and 29 Systemic Treatment: bevacizumab 5 mg/kg days 1 and 15
Intervention Type
Procedure
Intervention Name(s)
Radiation Therapy
Intervention Description
radiation 1.8 Gy/day or 28 fractions weeks 1-6
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin
Intervention Description
Systemic Treatment: oxaliplatin 85 mg/m2 days 1 and 15
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
Folinic acid
Intervention Description
Systemic Treatment: leucovorin 350 mg prior to FU on days 1 and 15
Primary Outcome Measure Information:
Title
Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment
Description
The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Description
Overall Survival (OS) is defined ad the Length of time, in months, that patients were alive from their first date of protocol treatment until death.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David R. Spigel, MD
Organizational Affiliation
SCRI Development Innovations, LLC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northeast Alabama Regional Medical Center
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
Northeast Arkansas Clinic
City
Jonesboro
State/Province
Arkansas
ZIP/Postal Code
72401
Country
United States
Facility Name
Florida Cancer Specialists
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33901
Country
United States
Facility Name
Integrated Community Oncology Network
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
Facility Name
Watson Clinic Center for Cancer Care and Research
City
Lakeland
State/Province
Florida
ZIP/Postal Code
33805
Country
United States
Facility Name
Northeast Georgia Medical Center
City
Gainesville
State/Province
Georgia
ZIP/Postal Code
30501
Country
United States
Facility Name
Wellstar Cancer Research
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Facility Name
Consultants in Blood Disorders and Cancer
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Consultants in Medical Oncology and Hematology
City
Drexel Hill
State/Province
Pennsylvania
ZIP/Postal Code
19026
Country
United States
Facility Name
Spartanburg Regional Medical Center
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
Facility Name
Chattanooga Oncology Hematology Associates
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37205
Country
United States
Facility Name
South Texas Oncology and Hematology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78258
Country
United States
Facility Name
Peninsula Cancer Institute
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23601
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21840771
Citation
Spigel DR, Bendell JC, McCleod M, Shipley DL, Arrowsmith E, Barnes EK, Infante JR, Burris HA 3rd, Greco FA, Hainsworth JD. Phase II study of bevacizumab and chemoradiation in the preoperative or adjuvant treatment of patients with stage II/III rectal cancer. Clin Colorectal Cancer. 2012 Mar;11(1):45-52. doi: 10.1016/j.clcc.2011.04.002. Epub 2011 Aug 15.
Results Reference
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Learn more about this trial

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

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