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

January 14, 2016 updated by: Assistance Publique - Hôpitaux de Paris

PRODIGE 22-ECKINOXE : Randomized Phase II Trial of Neoadjuvant FOLFOX 4 Versus FOLFOX 4 With Cetuximab Versus Immediate Surgery in Locally Advanced Colon Cancer

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

See Synopsis below

Study Type

Interventional

Enrollment (Anticipated)

186

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Paris, France, 94010
        • Recruiting
        • Hopital Henri Mondor
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pathologically confirmed colon adenocarcinoma (≥ 15 cm from the anal verge)
  • Assessment of RAS 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), patients with cancer treated by stomie de derivation may be included in the study.

DPD deficency

  • Absence of synchronous colorectal cancer
  • Age ≥ 18 years and < 76 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Histological tumor response in the primary tumor according to the simplified Tumor Regression Grade (TRG) of Ryan
Time Frame: 2 years
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)
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability and efficacy of the neoadjuvant chemotherapy
Time Frame: 9 years
  • Tolerability of the neoadjuvant therapies. SAFETY ISSUE
  • Postoperative morbidity at 60 days. SAFETY ISSUE
9 years
•Disease free survival and regression free survival at 3 years
Time Frame: 3 years
3 years
•Overall survival at 6 and 7 years
Time Frame: 6 and 7 years
6 and 7 years
•Quality of life (EORTC QLQ-C30, QLQ-CR29)
Time Frame: 5 years
5 years
•Quality and radicality of the surgical excision
Time Frame: 2 years
2 years
•Accuracy of pre-treatment CT scan staging and evaluation of radiological response to chemotherapy
Time Frame: 2 years
2 years
•Correlation between radiological and histological response
Time Frame: 2 years
2 years
•Evaluation of another histopathological grade
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Federation Francophone de Cancerologie Digestive
UNICANCER
Merck Serono S.A., Geneva
Association de Recherche Experimentale et Clinique en Chirurgie Digestive
Association Européenne de Recherche en Oncologie

Investigators

  • Principal Investigator: mehdi karoui, PH, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (Actual)

May 1, 2012

Study Completion (Anticipated)

February 1, 2021

Study Registration Dates

First Submitted

February 2, 2012

First Submitted That Met QC Criteria

August 29, 2012

First Posted (Estimate)

August 30, 2012

Study Record Updates

Last Update Posted (Estimate)

January 15, 2016

Last Update Submitted That Met QC Criteria

January 14, 2016

Last Verified

January 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P100131

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Colon Cancer

Clinical Trials on Perioperative simplified FOLFOX-4 chemotherapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Luxembourg

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe