Colorectal Cancer, Primary Peritoneal Cavity Cancer
Conditions
Keywords
adenocarcinoma of the colon, recurrent colon cancer, stage IV colon cancer, adenocarcinoma of the rectum, recurrent rectal cancer, stage IV rectal cancer, peritoneal carcinomatosis
Brief summary
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, 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. Giving more than one drug (combination chemotherapy) together with cetuximab may kill more tumor cells. PURPOSE: This phase II trial is studying how well chemotherapy given together with cetuximab works in treating patients undergoing surgery to remove peritoneal carcinomatosis from colorectal cancer.
Detailed description
OBJECTIVES: Primary * Determine the efficacy of systemic chemotherapy and cetuximab, in terms of progression-free survival at 3 years, in patients with completely resected peritoneal carcinomatosis of colorectal origin. Secondary * Determine the therapeutic strategy among patients who are or are not fit to receive chemotherapy. * Determine progression-free survival at 5 years and overall survival at 3 and 5 years in these patients. * Determine the overall tolerability (mortality, morbidity) of this regimen, including surgery, in these patients. OUTLINE: This is a multicenter study. Patients undergo complete resection of the peritoneal carcinomatosis. Beginning 4-8 weeks after surgery, patients receive cetuximab IV over 2.5 hours. Patients also receive FOLFOX chemotherapy comprising oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours. Treatment repeats every 2 weeks for up to 12 courses. After completion of study therapy, patients are followed every 4 months for 2 years and then every 6 months for 3 years.
Interventions
BIOLOGICALcetuximab
DRUGfluorouracil
DRUGleucovorin calcium
DRUGoxaliplatin
PROCEDUREadjuvant therapy
PROCEDUREtherapeutic conventional surgery
Sponsors
Assistance Publique - Hôpitaux de Paris
Centre Alexis Vautrin, Nancy
Centre Leon Berard
Institut Cancerologie de l'Ouest
Hôpital Haut-Lévêque
Clinique Médicale de Francheville
Institut Bergonié
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Combination Chemotherapy and Cetuximab in Treating Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed colorectal adenocarcinoma meeting the following criteria: * Exclusively peritoneal carcinomatosis (no other metastases) * Resectable disease * Primary tumor may be same in the same location as another synchronous carcinomatosis * Patients with metastatic disease who have been in complete remission for more than 1 year are eligible regardless of prior chemotherapy PATIENT CHARACTERISTICS: * WHO performance status 0-2 * Life expectancy ≥ 12 weeks * ANC ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Hemoglobin ≥ 10 g/dL * Bilirubin ≤ 1.25 times upper limit of normal (ULN) * AST and ALT ≤ 3 times ULN * Creatinine ≤ 1.25 times ULN * Creatinine clearance ≥ 30 mL/min * Not pregnant or nursing * Fertile patients must use effective contraception * No allergy, hypersensitivity, or other contraindication to leucovorin calcium, oxaliplatin, or fluorouracil * No other noncancerous disease that would preclude study therapy * Good nutritional status * No sensitive peripheral neuropathy with functional impairment * No hypoplasia or bone marrow failure * No clinically significant cardiovascular disease within the past year (e.g., unstable angina or myocardial infarction) * No other cancer within the past 5 years unless in complete remission with the exception of cervical carcinoma in situ or basal cell cancer * No patients deprived of liberty or under supervision * No psychological, social, familial, or geographical reasons prohibiting follow-up PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 1 year since prior adjuvant chemotherapy, including prior therapy with oxaliplatin and/or cetuximab * No prophylactic phenytoin (Dihydan®, Dilantin®) * No prior yellow fever vaccine * More than 1 month since participation in another study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression-free Survival (PFS) Time | Since surgery, up to 5 years | Progression-free survival time is defined as the time from the date of surgery to the date of progression (as per RECIST v1.1) or death of any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 30-day Mortality Rate | from the date of surgery up to 30 days | Rate of deaths observed within 30 days of surgery |
| Mean Number of Adverse Events Per Patient, Within 30 Days of Surgery | from the date of surgery up to 30 days | — |
| Overall Survival (OS) Time | from surgery, up to five years. | OS is the delay between surgery and death |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy + Cetuximab * Cetuximab 500 mg/m² IV
* Oxaliplatine 85 mg/m² IV
* L-folinique Acid 200 mg/m² (or 400 mg/m² for DL) IV
* 5-FU bolus 400 mg/m² IV
* 5-FU continu 2400 mg/m² IV. One cycle = 14 days. Up to 12 cycles. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 4 |
Baseline characteristics
| Characteristic | Chemotherapy + Cetuximab | — |
|---|---|---|
| Age, Continuous | 61.9 years STANDARD_DEVIATION 5.1 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment France | 14 participants | — |
| Sex: Female, Male Female | 4 Participants | — |
| Sex: Female, Male Male | 10 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 14 |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 6 / 14 |
Outcome results
Primary
Median Progression-free Survival (PFS) Time
Progression-free survival time is defined as the time from the date of surgery to the date of progression (as per RECIST v1.1) or death of any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Since surgery, up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy + Cetuximab | Median Progression-free Survival (PFS) Time | 12.2 months |
Secondary
30-day Mortality Rate
Rate of deaths observed within 30 days of surgery
Time frame: from the date of surgery up to 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy + Cetuximab | 30-day Mortality Rate | 0 Participants |
Secondary
Mean Number of Adverse Events Per Patient, Within 30 Days of Surgery
Time frame: from the date of surgery up to 30 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chemotherapy + Cetuximab | Mean Number of Adverse Events Per Patient, Within 30 Days of Surgery | 0.93 adverse events |
Secondary
Overall Survival (OS) Time
OS is the delay between surgery and death
Time frame: from surgery, up to five years.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy + Cetuximab | Overall Survival (OS) Time | 41.5 months |