Colorectal Cancer
Conditions
Keywords
colorectal, cancer
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.
Interventions
DRUGOxaliplatin
DRUGBevacizumab
DRUGCapecitabine
Sponsors
Hoffmann-La Roche
Genentech, Inc.
University of Southern California
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Time for Progression Free Survival | Up to 6 years | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3 or Higher Toxicity | Baseline, every 2 weeks of each cycle, and at end of treatment, up to 18 months. | Summary of grade 3 (per CTCAE v3.0) or higher toxicities which generally is described as a severe adverse reaction or symptom. |
Countries
United States
Participant flow
Recruitment details
Recruitment for this trial opened in February 2005 and closed in May 2009. All subjects were seen at USC.
Pre-assignment details
This trial has no pre-assignment. All subjects were given the same treatment.
Participants by arm
| Arm | Count |
|---|---|
| Oxaliplatin Followed by Bevacizumab, With Capecitabine oxaliplatin 85 mg/m2 q 14 days, followed by bevacizumab 5 mg/kg q 14 days, with capecitabine 750 mg/m2 bid daily | 63 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Lack of Efficacy | 8 |
Baseline characteristics
| Characteristic | Oxaliplatin Followed by Bevacizumab, With Capecitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 56 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 21 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 23 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 63 participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 63 / 63 |
| serious Total, serious adverse events | 51 / 63 |
Outcome results
Primary
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.
Time frame: Up to 6 years
Population: All enrolled participants who receive the first course of treatment are included in the analysis as per protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxaliplatin Followed by Bevacizumab, With Capecitabine | Median Time for Progression Free Survival | 15.8 Months |
Secondary
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.
Time frame: Baseline, every 2 weeks of each cycle, and at end of treatment, up to 18 months.
Population: All enrolled participants who receive the first course of treatment are included in the analysis as per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxaliplatin Followed by Bevacizumab, With Capecitabine | Number of Participants With Grade 3 or Higher Toxicity | 51 Participants |