Trial of Neoadjuvant Chemotherapy in Locally Advanced Colon Cancer (ECKINOXE)
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.
|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 Design:||Allocation: Randomized
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|
- 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)
- 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
- •Disease free survival and regression free survival at 3 years [ Time Frame: 3 years ]
- •Overall survival at 6 and 7 years [ Time Frame: 6 and 7 years ]
- •Quality of life (EORTC QLQ-C30, QLQ-CR29) [ Time Frame: 5 years ]
- •Quality and radicality of the surgical excision [ Time Frame: 2 years ]
- •Accuracy of pre-treatment CT scan staging and evaluation of radiological response to chemotherapy [ Time Frame: 2 years ]
- •Correlation between radiological and histological response [ Time Frame: 2 years ]
- •Evaluation of another histopathological grade [ Time Frame: 2 years ]
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||February 2021|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
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
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
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01675999
|Contact: Mehdi karoui, PH||+33 (0) 1 42 17 56 firstname.lastname@example.org|
|Hopital Henri Mondor||Recruiting|
|Paris, France, 94010|
|Contact: Mehdi KAROUI, PH +33 (0) 1 42 17 56 11 email@example.com|
|Principal Investigator:||mehdi karoui, PH||Assistance Publique - Hôpitaux de Paris|