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Bevacizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

Primary Purpose

Colorectal Cancer

Status
Unknown status
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
bevacizumab
capecitabine
fluorouracil
irinotecan hydrochloride
leucovorin calcium
Sponsored by
Southern Italy Cooperative Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage IV colon cancer, stage IV rectal cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed colorectal cancer

    • Metastatic disease that is not amenable to surgery
  • At least one measurable lesion according to RECIST criteria
  • No untreated brain metastases or spinal cord compression

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy ≥ 12 weeks
  • Hemoglobin ≥ 9.0 g/dL
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and/or ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
  • Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
  • PT-INR/PTT < 1.5 times ULN
  • Creatinine clearance > 50 mL/min OR serum creatinine ≤ 1.5 times ULN
  • Proteinuria on dipstick urinalysis < 2+ OR 24-hour urine protein ≤ 1g
  • Not pregnant or nursing
  • Negative pregnancy test
  • Must be accessible for treatment and follow-up
  • No history of inflammatory bowel disease and/or acute or subacute bowel occlusion
  • No serious non-healing wound, ulcer, or bone fracture
  • No evidence of bleeding diathesis or coagulopathy
  • No uncontrolled hypertension

  • No clinically significant cardiovascular disease including any of the following:

    • Cerebrovascular accident within the past 6 months
    • Myocardial infarction within the past 6 months
    • Unstable angina
    • New York Heart Association grade II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
  • No known allergy to Chinese hamster ovary cell proteins or any of the components of the study medications
  • No other malignancy within the past 5 years except basal cell and squamous cell skin cancer or carcinoma in situ of the cervix
  • No significant traumatic injury within the past 28 days
  • No substance abuse or medical, psychological, or social conditions that may interfere with participation in the study or the evaluation of study results
  • Able to swallow oral medications

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 6 months since prior adjuvant treatment
  • No prior irinotecan and/or bevacizumab during prior adjuvant therapy
  • No prior cytotoxic drugs for the metastatic disease
  • More than 10 days since prior and no concurrent anticoagulants for therapeutic purposes
  • No chronic, daily treatment with high-dose aspirin (> 325 mg/day) or other medications known to predispose to gastrointestinal ulceration
  • No treatment with any investigational drug within the past 30 days
  • No major surgical procedure or open biopsy within the past 28 days or anticipated need for a major surgical procedure during the course of the study

Sites / Locations

  • Southern Italy Cooperative Oncology GroupRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm I

Arm II

Arm Description

Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 1 hour and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients receive bevacizumab and FOLFIRI chemotherapy (B-FOLFIRI) as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes on day 1 and oral capecitabine once every 12 hours on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Time to failure of strategy

Secondary Outcome Measures

Response according to RECIST criteria
Duration of response
Progression-free survival
Safety according to NCI CTCAE v3.0
Quality of life as assessed by EORTC QLQ-C30 questionnaire (v 3.0) at baseline, every 3 months during induction chemotherapy, and at discontinuation of treatment

Full Information

First Posted
November 22, 2008
Last Updated
August 23, 2013
Sponsor
Southern Italy Cooperative Oncology Group
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1. Study Identification

Unique Protocol Identification Number
NCT00797485
Brief Title
Bevacizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Metastatic Colorectal Cancer That Cannot Be Removed By Surgery
Official Title
Maintenance and Reinduction Chemotherapy With Avastin in Metastatic Colon Cancer: The MARTHA (SICOG 0803) Trial
Study Type
Interventional

2. Study Status

Record Verification Date
June 2009
Overall Recruitment Status
Unknown status
Study Start Date
July 2008 (undefined)
Primary Completion Date
July 2011 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Southern Italy Cooperative Oncology Group

4. Oversight

5. Study Description

Brief Summary
RATIONALE: 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. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase III trial is studying how well giving induction therapy with bevacizumab together with combination chemotherapy with or without capecitabine followed by bevacizumab maintenance therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.
Detailed Description
OBJECTIVES: Primary To compare two strategies of induction bio-chemotherapy followed by the same maintenance biotherapy in terms of time to failure in patients with previously untreated metastatic colorectal cancer. Secondary To compare the two arms of treatment in terms of response rate, duration of responses, progression-free survival, safety, and quality of life of these patients. OUTLINE: This is a multicenter study. Patients are stratified according to treatment center, performance status (0 vs 1), and number of metastatic sites (1 vs ≥ 2). Patients are randomized to 1 of 2 induction therapy arms. Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 1 hour and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive bevacizumab and FOLFIRI chemotherapy (B-FOLFIRI) as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes on day 1 and oral capecitabine once every 12 hours on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. In both arms, patients achieving stable disease after completion of 6 months of induction therapy proceed to maintenance therapy. Maintenance therapy: Patients receive bevacizumab IV over 30-90 minutes every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. During or after completion of maintenance therapy, patients with tumor regrowth that is not classified as disease progression from baseline and who achieved partial or complete response during or after their induction therapy proceed to reinduction therapy. Reinduction therapy: Patients receive B-FOLFIRI as described previously. Quality of life is assessed at baseline, every 3 months during induction therapy, and at discontinuation of study therapy. After completion of study therapy, patients are followed for up to 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
stage IV colon cancer, stage IV rectal cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Masking
None (Open Label)
Allocation
Randomized
Enrollment
672 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Active Comparator
Arm Description
Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 1 hour and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm II
Arm Type
Experimental
Arm Description
Patients receive bevacizumab and FOLFIRI chemotherapy (B-FOLFIRI) as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes on day 1 and oral capecitabine once every 12 hours on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
capecitabine
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Time to failure of strategy
Secondary Outcome Measure Information:
Title
Response according to RECIST criteria
Title
Duration of response
Title
Progression-free survival
Title
Safety according to NCI CTCAE v3.0
Title
Quality of life as assessed by EORTC QLQ-C30 questionnaire (v 3.0) at baseline, every 3 months during induction chemotherapy, and at discontinuation of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed colorectal cancer Metastatic disease that is not amenable to surgery At least one measurable lesion according to RECIST criteria No untreated brain metastases or spinal cord compression PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy ≥ 12 weeks Hemoglobin ≥ 9.0 g/dL ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Total bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and/or ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases present) Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN if liver metastases present) PT-INR/PTT < 1.5 times ULN Creatinine clearance > 50 mL/min OR serum creatinine ≤ 1.5 times ULN Proteinuria on dipstick urinalysis < 2+ OR 24-hour urine protein ≤ 1g Not pregnant or nursing Negative pregnancy test Must be accessible for treatment and follow-up No history of inflammatory bowel disease and/or acute or subacute bowel occlusion No serious non-healing wound, ulcer, or bone fracture No evidence of bleeding diathesis or coagulopathy No uncontrolled hypertension No clinically significant cardiovascular disease including any of the following: Cerebrovascular accident within the past 6 months Myocardial infarction within the past 6 months Unstable angina New York Heart Association grade II-IV congestive heart failure Serious cardiac arrhythmia requiring medication No known allergy to Chinese hamster ovary cell proteins or any of the components of the study medications No other malignancy within the past 5 years except basal cell and squamous cell skin cancer or carcinoma in situ of the cervix No significant traumatic injury within the past 28 days No substance abuse or medical, psychological, or social conditions that may interfere with participation in the study or the evaluation of study results Able to swallow oral medications PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 6 months since prior adjuvant treatment No prior irinotecan and/or bevacizumab during prior adjuvant therapy No prior cytotoxic drugs for the metastatic disease More than 10 days since prior and no concurrent anticoagulants for therapeutic purposes No chronic, daily treatment with high-dose aspirin (> 325 mg/day) or other medications known to predispose to gastrointestinal ulceration No treatment with any investigational drug within the past 30 days No major surgical procedure or open biopsy within the past 28 days or anticipated need for a major surgical procedure during the course of the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pasquale Comella, MD
Organizational Affiliation
Istituto Nazionale per lo Studio e la Cura dei Tumori
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southern Italy Cooperative Oncology Group
City
Naples
ZIP/Postal Code
80131
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pasquale Comella, MD
Phone
39-81-590-3227
Email
pasqualecomella@libero.it

12. IPD Sharing Statement

Learn more about this trial

Bevacizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

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