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Study of Oxaliplatin, Capecitabine and Bevacizumab as First Line Treatment for Patients With Advanced Colorectal Cancer

Primary Purpose

Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Oxaliplatin
Bevacizumab
Capecitabine
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring colorectal, cancer

Eligibility Criteria

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

Inclusion Criteria: Histologically or cytologically confirmed metastatic or recurrent colorectal tumors with no previous treatment for advanced disease. Age greater than or equal to 18 years SWOG performance status 0-1. At least one measurable lesion according to the RECIST criteria which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Minimum indicator lesion size: > 10 mm measured by spiral CT or >20mm measured by conventional techniques. Have a negative serum pregnancy test within 7 days prior to initiation of chemotherapy (female patients of childbearing potential). Availability of tumor biopsy (paraffin embedded or fresh frozen) at the time of diagnosis and/or prior to study entry is required. Patients must agree to have a 20 cc blood sample drawn in addition to routine labs with each cycle of chemotherapy. Exclusion Criteria: Pregnant or lactating woman. Life expectancy < 3 months. Serious, uncontrolled, concurrent infection(s) or illness(es) Any prior oxaliplatin treatment, with the exception of adjuvant therapy given > 12 months prior to the beginning of study therapy Prior unanticipated severe reaction to fluoropyrimidine therapy, known hypersensitivity to 5-fluorouracil, or known DPD deficiency Prior unanticipated severe reaction or hypersensitivity to platinum based compounds. Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer. Current, recent (within 4 weeks of first infusion on this study) or planned participation in an investigational drug study. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) within the last 6 months. History of clinically significant interstitial lung disease and/or pulmonary fibrosis. History of persistent neurosensory disorder including but not limited to peripheral neuropathy. Presence of central nervous system or brain mets. Major surgery, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study. Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome. Any of the following laboratory values: Abnormal hematologic values (neutrophils < 1.5 x 109/L, platelet count < 100 x 109/L) Urine protein: creatinine ratio >/= 1.0 Impaired renal function with estimated creatinine clearance < 30 ml/min as calculated with Cockroft et Gault equation: Serum bilirubin > 1.5 x upper normal limit. ALT, AST > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases) Alkaline phosphatase > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases or > 10 x upper normal limit in the case of bone disease) Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0 Blood pressure > 150/100 mmHg Unstable angina New York Heart Association (NYHA) Grade II or greater congestive heart failure History of myocardial infarction or stroke within 6 months Clinically significant peripheral vascular disease Evidence of bleeding diathesis or coagulopathy History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to Day 0. Serious, non-healing wound, ulcer or bone fracture Carcinoma of any histology in close proximity to a major vessel, cavitation or history of hemoptysis. Completion of previous adjuvant chemotherapy regimen < four weeks prior to the start of study treatment (within six weeks of study treatment for mitomycin C and nitroureas), or with related toxicities unresolved prior to the start of study treatment.

Sites / Locations

  • U.S.C./Norris Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Oxaliplatin, followed by Bevacizumab with Capecitabine

Arm Description

oxaliplatin 85 mg/m2 q 14 days, followed by bevacizumab 5 mg/kg q 14 days, with capecitabine 750 mg/m2 bid daily

Outcomes

Primary Outcome Measures

Median Time for Progression Free Survival
Progression-free survival was measured from the start of treatment until the time the subject is first recorded as having disease progression (progression = 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed or baseline, progression of non-measurable disease in the opinion of treating physician, appearance of new lesion/site, death due to disease), or death due to any cause. If a subject has not progressed or died, progression-free survival was censored at the time of last follow-up or the start of another treatment, whichever came first.

Secondary Outcome Measures

Number of Participants With Grade 3 or Higher Toxicity
Summary of grade 3 (per CTCAE v3.0) or higher toxicities which generally is described as a severe adverse reaction or symptom.

Full Information

First Posted
September 7, 2005
Last Updated
July 22, 2014
Sponsor
University of Southern California
Collaborators
Hoffmann-La Roche, Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00159432
Brief Title
Study of Oxaliplatin, Capecitabine and Bevacizumab as First Line Treatment for Patients With Advanced Colorectal Cancer
Official Title
Phase II Study of Oxaliplatin, Capecitabine and Bevacizumab as First Line Treatment for Patients With Advanced Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
February 2005 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southern California
Collaborators
Hoffmann-La Roche, Genentech, Inc.

4. Oversight

5. Study Description

Brief Summary
This study is for people with colorectal cancer, who have tumors that cannot be completely removed by surgery. This study is being done to find out how long it takes tumors to grow after patients receive the drugs capecitabine, oxaliplatin and bevacizumab. Capecitabine (also called Xeloda) is a drug that has been approved by the FDA for treatment of advanced colorectal cancer. Capecitabine prevents some colorectal cancer cancer cells from reproducing, and causes some of them to die. Oxaliplatin (also called Eloxatin) has also been approved by the FDA for treatment of advanced colorectal cancer. Oxaliplatin prevents some colorectal cancer cells from reproducing. Bevacizumab is an investigational drug. Bevacizumab is an antibody (a protein that acts against a specific substance) directed against vascular endothelial growth factor (VEGF). VEGF promotes the growth of blood vessels that bring nutrients to cells. Bevacizumab inhibits the growth of colon cancer cells, by blocking the effects of VEGF. The combination of the drugs used in this study is experimental. The purpose of this study is to see how long it takes patients' tumors to grow when they are taking this combination of drugs.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
colorectal, cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Oxaliplatin, followed by Bevacizumab with Capecitabine
Arm Type
Experimental
Arm Description
oxaliplatin 85 mg/m2 q 14 days, followed by bevacizumab 5 mg/kg q 14 days, with capecitabine 750 mg/m2 bid daily
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Primary Outcome Measure Information:
Title
Median Time for Progression Free Survival
Description
Progression-free survival was measured from the start of treatment until the time the subject is first recorded as having disease progression (progression = 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed or baseline, progression of non-measurable disease in the opinion of treating physician, appearance of new lesion/site, death due to disease), or death due to any cause. If a subject has not progressed or died, progression-free survival was censored at the time of last follow-up or the start of another treatment, whichever came first.
Time Frame
Up to 6 years
Secondary Outcome Measure Information:
Title
Number of Participants With Grade 3 or Higher Toxicity
Description
Summary of grade 3 (per CTCAE v3.0) or higher toxicities which generally is described as a severe adverse reaction or symptom.
Time Frame
Baseline, every 2 weeks of each cycle, and at end of treatment, up to 18 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed metastatic or recurrent colorectal tumors with no previous treatment for advanced disease. Age greater than or equal to 18 years SWOG performance status 0-1. At least one measurable lesion according to the RECIST criteria which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Minimum indicator lesion size: > 10 mm measured by spiral CT or >20mm measured by conventional techniques. Have a negative serum pregnancy test within 7 days prior to initiation of chemotherapy (female patients of childbearing potential). Availability of tumor biopsy (paraffin embedded or fresh frozen) at the time of diagnosis and/or prior to study entry is required. Patients must agree to have a 20 cc blood sample drawn in addition to routine labs with each cycle of chemotherapy. Exclusion Criteria: Pregnant or lactating woman. Life expectancy < 3 months. Serious, uncontrolled, concurrent infection(s) or illness(es) Any prior oxaliplatin treatment, with the exception of adjuvant therapy given > 12 months prior to the beginning of study therapy Prior unanticipated severe reaction to fluoropyrimidine therapy, known hypersensitivity to 5-fluorouracil, or known DPD deficiency Prior unanticipated severe reaction or hypersensitivity to platinum based compounds. Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer. Current, recent (within 4 weeks of first infusion on this study) or planned participation in an investigational drug study. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) within the last 6 months. History of clinically significant interstitial lung disease and/or pulmonary fibrosis. History of persistent neurosensory disorder including but not limited to peripheral neuropathy. Presence of central nervous system or brain mets. Major surgery, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study. Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome. Any of the following laboratory values: Abnormal hematologic values (neutrophils < 1.5 x 109/L, platelet count < 100 x 109/L) Urine protein: creatinine ratio >/= 1.0 Impaired renal function with estimated creatinine clearance < 30 ml/min as calculated with Cockroft et Gault equation: Serum bilirubin > 1.5 x upper normal limit. ALT, AST > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases) Alkaline phosphatase > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases or > 10 x upper normal limit in the case of bone disease) Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0 Blood pressure > 150/100 mmHg Unstable angina New York Heart Association (NYHA) Grade II or greater congestive heart failure History of myocardial infarction or stroke within 6 months Clinically significant peripheral vascular disease Evidence of bleeding diathesis or coagulopathy History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to Day 0. Serious, non-healing wound, ulcer or bone fracture Carcinoma of any histology in close proximity to a major vessel, cavitation or history of hemoptysis. Completion of previous adjuvant chemotherapy regimen < four weeks prior to the start of study treatment (within six weeks of study treatment for mitomycin C and nitroureas), or with related toxicities unresolved prior to the start of study treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Syma Iqbal, M.D.
Organizational Affiliation
U.S.C. Norris Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
U.S.C./Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22622147
Citation
Hurwitz H, Mitchell EP, Cartwright T, Kwok A, Hu S, McKenna E, Patt YZ. A randomized, phase II trial of standard triweekly compared with dose-dense biweekly capecitabine plus oxaliplatin plus bevacizumab as first-line treatment for metastatic colorectal cancer: XELOX-A-DVS (dense versus standard). Oncologist. 2012;17(7):937-46. doi: 10.1634/theoncologist.2012-0071. Epub 2012 May 23.
Results Reference
derived

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Study of Oxaliplatin, Capecitabine and Bevacizumab as First Line Treatment for Patients With Advanced Colorectal Cancer

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