Trial of Neoadjuvant Chemotherapy in Locally Advanced Colon Cancer (ECKINOXE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2012 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborators:
Federation Francophone de Cancerologie Digestive
UNICANCER
Association de Recherche Experimentale et Clinique en Chirurgie Digestive
Association Européenne de Recherche en Oncologie
Merck Serono S.A., Geneva
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01675999
First received: February 2, 2012
Last updated: July 25, 2014
Last verified: January 2012
  Purpose

In patients with locally advanced colon cancer (high risk stage II and stage III), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 30-40% of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for locally advanced colon cancer and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery.

ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy (response rate) and feasibility (safety, tolerance) of these two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4+Cetuximab) in a neoadjuvant strategy in patients with locally advanced colon cancer. Control arm includes patients for whom standard treatment comprises surgery followed by adjuvant FOLFOX-4 chemotherapy. This phase II study will assess the feasibility of a neoadjuvant strategy in these patients and determine which neoadjuvant regimen is the most effective in terms of response rate.


Condition Intervention Phase
Colon Cancer
Locally Advanced Malignant Neoplasm
Other: Perioperative simplified FOLFOX-4 chemotherapy
Other: Perioperative FOLFOX4+Cetuximab chemotherapy
Other: Surgery followed by FOLFOX4 chemotherapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PRODIGE 22-ECKINOXE : Randomized Phase II Trial of Neoadjuvant FOLFOX 4 Versus FOLFOX 4 With Cetuximab Versus Immediate Surgery in Locally Advanced Colon Cancer

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Histological tumor response in the primary tumor according to the simplified Tumor Regression Grade (TRG) of Ryan [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    This primary outcome will be evaluated on the surgical specimens: Immediately after surgery (arm C) or after neoadjuvant chemotherapy (4 cycles) and surgery (arms A and B)


Secondary Outcome Measures:
  • Safety and tolerability and efficacy of the neoadjuvant chemotherapy [ Time Frame: 9 years ] [ Designated as safety issue: Yes ]
    • Tolerability of the neoadjuvant therapies. SAFETY ISSUE
    • Postoperative morbidity at 60 days. SAFETY ISSUE

  • •Disease free survival and regression free survival at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • •Overall survival at 6 and 7 years [ Time Frame: 6 and 7 years ] [ Designated as safety issue: Yes ]
  • •Quality of life (EORTC QLQ-C30, QLQ-CR29) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • •Quality and radicality of the surgical excision [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • •Accuracy of pre-treatment CT scan staging and evaluation of radiological response to chemotherapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • •Correlation between radiological and histological response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • •Evaluation of another histopathological grade [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 186
Study Start Date: May 2012
Estimated Study Completion Date: February 2021
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

Perioperative simplified FOLFOX-4 chemotherapy

- Simplified FOLFOX-4 (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV bolus 5-FU 400 mg/m2 and IV infusional 5-FU 2400 mg/m2 over 46h) for 4 cycles followed by colectomy (3 to 5 weeks after) followed by simplified FOLFOX-4 (8 cycles).

Other: Perioperative simplified FOLFOX-4 chemotherapy
Preoperative chemotherapy
Other Name: Perioperative simplified FOLFOX-4 chemotherapy
Experimental: 2
Perioperative FOLFOX4+Cetuximab chemotherapy Simplified FOLFOX-4 (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV bolus 5-FU 400 mg/m2 and IV infusional 5-FU 2400 mg/m2 over 46h)+ Cetuximab (IV 500 mg/m2 every 2 weeks) for 4 cycles followed by colectomy (3 to 5 weeks after), followed by simplified FOLFOX-4 + Cetuximab (8 cycles).
Other: Perioperative FOLFOX4+Cetuximab chemotherapy
Preoperative chemotherapy
Other Name: Perioperative FOLFOX4+Cetuximab chemotherapy
3
Surgery followed by FOLFOX4 chemotherapy No preoperative chemotherapy Colectomy (maximum 4 weeks after randomization) followed by simplified FOLFOX-4 (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV bolus 5-FU 400 mg/m2 and IV infusional 5-FU 2400 mg/m2 over 46h) for 12 cycles.
Other: Surgery followed by FOLFOX4 chemotherapy
Preoperative chemotherapy
Other Name: Surgery followed by FOLFOX4 chemotherapy

Detailed Description:

See Synopsis below

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically confirmed colon adenocarcinoma (≥ 15 cm from the anal verge)
  • Assessment of KRAS status of the primary colon cancer on biopsies (WT or mutated)
  • Colon cancer classified: poor prognosis T3 (T3 bad) - T4 and/ or N2 by abdominal CT scan.
  • Non metastatic colon cancer (lung, liver, peritoneal)
  • Non complicated primary tumor (obstruction, perforation, bleeding)
  • Absence of synchronous colorectal cancer
  • Age ≥ 18 years and < 71 years
  • ECOG performance status 0-1
  • No prior chemotherapy within the last 5 years
  • No prior abdominal or pelvic irradiation within the last 5 years
  • Life expectancy of 5 years or more
  • No history of colorectal cancer within the last 5 years
  • Patients with childbearing potential should use effective contraception during the study and the following 6 months
  • White blood cell count of 3 x 109/L or more with neutrophils of1.5 x 109/L or more, platelet count of 100 x 109/L or more, hemoglobin of 9 g/dL (5,6 mmol/l) or more
  • Total bilirubin of 1.5 x ULN (upper limit of normal) or less
  • ASAT and ALAT of 2.5 x ULN or less
  • Alkaline phosphatase of 1.5 x ULN or less
  • Serum creatinine of 1.5 x ULN or less
  • Signed written informed consent obtained prior to any study specific screening procedures

Exclusion Criteria:

  • contra-indication to iodinated contrast medium injection including allergy to iodinated contrast medium and renal insufficiency proscribing iodinated injection
  • Age > 70 years
  • Rectal cancer located within 15 cm from the anal verge by endoscopy or under the peritoneal reflection at surgery or having received radiation therapy prior to surgery
  • Complicated primary colon cancer (obstruction, bleeding, perforation)
  • Synchronous colorectal cancer
  • Metastatic spread at baseline assessment (lung, liver, peritoneal)
  • History or current evidence on physical examination of central nervous system disease or peripheral neuropathy ≥ grade 1 Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0
  • Known hypersensitivity reaction to any of the components of study treatments
  • Presence of inflammatory bowel disease
  • HNPCC syndrome or polyposis
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to study treatment start. Incompletely healed wounds or anticipation of the need for major surgical procedure during the course of the study
  • Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia
  • Pregnancy (absence to be confirmed by ß-hCG test) or breast-feeding period
  • Previous malignancy in the last 5 years
  • Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent
  • Any significant disease which, in the investigator's opinion, would exclude the patient from the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01675999

Contacts
Contact: Mehdi karoui, PH +33 (0) 1 42 17 56 11 mehdi.karoui@gmail.com

Locations
France
Hopital Henri Mondor Recruiting
Paris, France, 94010
Contact: Mehdi KAROUI, PH    +33 (0) 1 42 17 56 11    mehdi.karoui@gmail.com   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Federation Francophone de Cancerologie Digestive
UNICANCER
Association de Recherche Experimentale et Clinique en Chirurgie Digestive
Association Européenne de Recherche en Oncologie
Merck Serono S.A., Geneva
Investigators
Principal Investigator: mehdi karoui, PH Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01675999     History of Changes
Other Study ID Numbers: P100131
Study First Received: February 2, 2012
Last Updated: July 25, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Neoadjuvant chemotherapy
Locally advanced malignant neoplasm
colon cancer

Additional relevant MeSH terms:
Neoplasms
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Colonic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014