NCT02842580

De-escalation Chemotherapies Versus Escalation in Non Pre-treated Unresectable Patients With Metastatic Colorectal Cancer

Randomized Phase II Study Assessing the Efficacy and Safety of 2 Therapeutic Strategies Combining Bevacizumab With Chemotherapy: De-escalation Versus Escalation in Patients With Non-pretreated Unresectable Metastatic Colorectal Cancer

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: Federation Francophone de Cancerologie Digestive · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The intensity of tumour response appears to be correlated with the feasibility and the duration of a therapeutic pause or of a reduced maintenance therapy maintained until progression in patients initially controlled by so-called "induction" chemotherapy. Bevacizumab combined with cytotoxic chemotherapy (5-FU, irinotecan and/or oxaliplatin) has shown that it is possible to improve the tumour response rate and patient prognosis in 1st and 2nd lines. With a very favourable safety profile , it is an excellent candidate as induction treatment and also as maintenance treatment. Prospective data from recent trials have actually demonstrated improvement in PFS and/or overall survival with bevacizumab maintenance alone or in combination with 5FU (or capecitabine) after induction chemotherapy (FOLFIRI or FOLFOX + bevacizumab). At the same time, the maintenance of anti-angiogenic pressure after progression in 1st line metastatic has demonstrated its benefit in terms of PFS and overall survival. Bevacizumab maintenance in 2nd line metastatic, despite progression, thus appears to be a valid strategy.

Detailed description

Thus, the objective of this work is to combine continuous blocking of angiogenesis by bevacizumab given on the first 3 metastatic lines in a randomised phase II trial evaluating a "descending" strategy of immediate optimisation by 4 cycles of FOLFOXIRI-bevacizumab and 4 cycles of FOLFIRI-bevacizumab, followed by maintenance treatment with 5FU-bevacizumab until progression (re-introduction of induction in case of progression) and evaluate an "ascending" strategy with 5FU-bevacizumab immediately followed, at progression, by the introduction of irinotecan, then oxaliplatin, with maintenance of blocking of angiogenesis by bevacizumab.

Conditions

• Colorectal Neoplasms

Interventions

Type	Name	Description
DRUG	5 FLUOROURACYL	Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as a 2 hr infusion. The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2). The cycles will last 14 days. For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.
DRUG	acide folinique	200 mg/m² if Elvorine
DRUG	irinotecan	Irinotecan is administered IV at a dose of 180 mg/m² over 90 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with irinotecan. The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2). The cycles will last 14 days.
DRUG	Oxaliplatin	Oxaliplatin is administered IV at a dose of 85 mg/m² over 120 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with oxaliplatin. The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2). The cycles will last 14 days.
DRUG	capécitabine	For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.
DRUG	bevacizumab	Bevacizumab is administered IV at a dose of 5 mg/kg over 90 min at cycle 1, then 60 min at cycle 2 and 30 min in subsequent cycles. Bevacizumab is administered every 2 weeks before the start of chemotherapy

Timeline

• Start date: 2016-09-01
• Primary completion: 2020-10-01
• Completion: 2020-10-01
• First posted: 2016-07-25
• Last updated: 2024-07-10
• Results posted: 2024-07-10

Locations

11 sites across 1 country: France