COCHISE: Chemotherapy and Cetuximab in Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer

• Sponsor: Institut Bergonié (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00766142
• Collaborator: Assistance Publique - Hôpitaux de Paris (Other), Centre Alexis Vautrin, Nancy (Other), Centre Leon Berard (Other), Institut Cancerologie de l'Ouest (Other), Hôpital Haut-Lévêque (Other), Clinique Francheville, Périgueux (Other)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 76.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer; Primary Peritoneal Cavity Cancer	Biological: cetuximab; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Procedure: adjuvant therapy; Procedure: therapeutic conventional surgery	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Combination Chemotherapy and Cetuximab in Treating Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal CancerCombination Chemotherapy and Cetuximab in Treating Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Phase II Study Evaluating Systemic Chemotherapy in Combination With Cetuximab as Adjuvant Treatment in Patients With Completely Surgically Resected Peritoneal Carcinomatosis of Colorectal Origin
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Sep 17, 2013
• Actual Study Completion Date: Sep 17, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemotherapy + Cetuximab Surgery + Chemotherapy + Cetuximab	Biological: cetuximab; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Procedure: adjuvant therapy; Procedure: therapeutic conventional surgery

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 30-day Mortality Rate [from the date of surgery up to 30 days]

   Rate of deaths observed within 30 days of surgery

2. Mean Number of Adverse Events Per Patient, Within 30 Days of Surgery [from the date of surgery up to 30 days]

3. Overall Survival (OS) Time [from surgery, up to five years.]

   OS is the delay between surgery and death

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institut Bergonie	Bordeaux		France	33076

Sponsors and Collaborators

• Institut Bergonié
• Assistance Publique - Hôpitaux de Paris
• Centre Alexis Vautrin, Nancy
• Centre Leon Berard
• Institut Cancerologie de l'Ouest
• Hôpital Haut-Lévêque
• Clinique Francheville, Périgueux

Investigators

• Study Chair: Serge Evrard, Institut Bergonié

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Institut Bergonié
• ClinicalTrials.gov Identifier: NCT00766142
• Other Study ID Numbers: CDR0000599511; IB-COCHISE-I; IB-2007-20; EUDRACT-2006-003900; MERCK-IB-COCHISE-I
• First Posted: Oct 3, 2008
• Last Update Posted: Jan 26, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Institut Bergonié: adenocarcinoma of the colon; recurrent colon cancer; stage IV colon cancer; adenocarcinoma of the rectum; recurrent rectal cancer; stage IV rectal cancer; peritoneal carcinomatosis
• Additional relevant MeSH terms: Colorectal Neoplasms; Carcinoma; Peritoneal Neoplasms; Leucovorin; Fluorouracil; Oxaliplatin; Cetuximab; Calcium; Levoleucovorin

Study Results

Participant Flow

Arm/Group Title	Chemotherapy + Cetuximab
Arm/Group Description	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.
Period Title: Overall Study
STARTED	18
COMPLETED	14
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Chemotherapy + Cetuximab
Arm/Group Description	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.
Overall Participants	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.9 (5.1)
Sex: Female, Male (Count of Participants)
Female	4 28.6%
Male	10 71.4%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
France	14 100%

Outcome Measures

1. Primary Outcome

Title	Median Progression-free Survival (PFS) Time
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy + Cetuximab
Arm/Group Description	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.
Measure Participants	14
Median (95% Confidence Interval) [months]	12.2

2. Secondary Outcome

Title	30-day Mortality Rate
Description	Rate of deaths observed within 30 days of surgery
Time Frame	from the date of surgery up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy + Cetuximab
Arm/Group Description	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.
Measure Participants	14
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Mean Number of Adverse Events Per Patient, Within 30 Days of Surgery
Time Frame	from the date of surgery up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy + Cetuximab
Arm/Group Description	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.
Measure Participants	14
Mean (95% Confidence Interval) [adverse events]	0.93

4. Secondary Outcome

Title	Overall Survival (OS) Time
Description	OS is the delay between surgery and death
Time Frame	from surgery, up to five years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy + Cetuximab
Arm/Group Description	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.
Measure Participants	14
Median (95% Confidence Interval) [months]	41.5

Adverse Events

Time Frame	from surgery, up to 5 years
Adverse Event Reporting Description	Adverse Events were monitored/assessed without regard to the specific Adverse Event Term,
Arm/Group Title	Chemotherapy + Cetuximab
Arm/Group Description	cetuximab fluorouracil leucovorin calcium oxaliplatin adjuvant therapy therapeutic conventional surgery
All Cause Mortality
	Chemotherapy + Cetuximab
	Affected / at Risk (%)	# Events
Total	8/14 (57.1%)
Serious Adverse Events
	Chemotherapy + Cetuximab
	Affected / at Risk (%)	# Events
Total	6/14 (42.9%)
Gastrointestinal disorders
Gastrointestinal disorders - Other	1/14 (7.1%)	1
Vomiting	1/14 (7.1%)	1
Diarrhea	1/14 (7.1%)	2
General disorders
General disorders and administration site conditions - Other	1/14 (7.1%)	1
Immune system disorders
Anaphylaxis	2/14 (14.3%)	2
Injury, poisoning and procedural complications
Intraoperative gastrointestinal injury	1/14 (7.1%)	1
Renal and urinary disorders
Urinary fistula	1/14 (7.1%)	1
Vascular disorders
Vascular disorders - Other	1/14 (7.1%)	1
Other (Not Including Serious) Adverse Events
	Chemotherapy + Cetuximab
	Affected / at Risk (%)	# Events
Total	14/14 (100%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other	1/14 (7.1%)	1
Anemia	3/14 (21.4%)	3
Gastrointestinal disorders
Constipation	1/14 (7.1%)	1
Diarrhea	1/14 (7.1%)	1
Gastritis	9/14 (64.3%)	10
Small intestinal mucositis	4/14 (28.6%)	4
Nausea	3/14 (21.4%)	3
Vomiting	4/14 (28.6%)	5
General disorders
General disorders and administration site conditions - Other	1/14 (7.1%)	1
Fatigue	10/14 (71.4%)	10
Fever	2/14 (14.3%)	2
Chills	2/14 (14.3%)	2
Injection site reaction	1/14 (7.1%)	1
Edema limbs	1/14 (7.1%)	1
Pain	2/14 (14.3%)	2
Pain, other	1/14 (7.1%)	1
Immune system disorders
Allergic reaction	2/14 (14.3%)	2
Injury, poisoning and procedural complications
burn	1/14 (7.1%)	1
Injury, poisoning and procedural complications - Other	1/14 (7.1%)	1
Investigations
White blood cell decreased	2/14 (14.3%)	2
Neutrophil count decreased	3/14 (21.4%)	4
Platelet count decreased	2/14 (14.3%)	2
Weight loss	1/14 (7.1%)	1
Metabolism and nutrition disorders
Anorexia	3/14 (21.4%)	3
Dehydration	1/14 (7.1%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other	1/14 (7.1%)	3
Trismus	2/14 (14.3%)	2
Nervous system disorders
Dysgeusia	1/14 (7.1%)	1
Peripheral sensory neuropathy	13/14 (92.9%)	16
Reproductive system and breast disorders
Vaginal discharge	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	2/14 (14.3%)	2
Dyspnea	1/14 (7.1%)	1
Pneumonitis	1/14 (7.1%)	1
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other	7/14 (50%)	7
Dry skin	4/14 (28.6%)	4
Pruritus	1/14 (7.1%)	1
Rash maculo-papular	1/14 (7.1%)	1
Rash acneiform	7/14 (50%)	7
Palmar-plantar erythrodysesthesia syndrome	7/14 (50%)	7
Urticaria	1/14 (7.1%)	1
Vascular disorders
Hypotension	2/14 (14.3%)	2
Flushing	4/14 (28.6%)	4
Hot flashes	1/14 (7.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.