Clinical Trials /

Trial of Neoadjuvant Chemotherapy in Locally Advanced Colon Cancer

NCT01675999

Description:

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.

Related Conditions:
  • Colon Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial of Neoadjuvant Chemotherapy in Locally Advanced Colon Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: P100131
  • NCT ID: NCT01675999

Conditions

  • Colon Cancer
  • Locally Advanced Malignant Neoplasm

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.

Detailed Description

      See Synopsis below
    

Trial Arms

NameTypeDescriptionInterventions
1ExperimentalPerioperative 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).
    2ExperimentalPerioperative 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).
      3OtherSurgery 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.

        Eligibility Criteria

                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.
              
        Maximum Eligible Age:76 Years
        Minimum Eligible Age:18 Years
        Eligible Gender:All
        Healthy Volunteers:No

        Primary Outcome Measures

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

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

        Details

        Phase:Phase 2
        Primary Purpose:Interventional
        Overall Status:Recruiting
        Lead Sponsor:Assistance Publique - Hôpitaux de Paris

        Trial Keywords

        • Neoadjuvant chemotherapy
        • Locally advanced malignant neoplasm
        • colon cancer

        Last Updated

        January 14, 2016