Strategic 1-multi-line therapy trial in unresectable wild-type RAS metastatic colorectal cancer 				: A gercor randomized open-label phase III study.

BackgroundFOLFOXIRI plus bevacizumab is considered a standard option in the upfront treatment of clinically selected patients with metastatic colorectal cancer irrespective ofRASandBRAFmolecular status. The randomised MACBETH and VOLFI studies showed that a modified FOLFOXIRI regimen in combination with cetuximab or panitumumab, respectively, achieved high therapeutic activity inRASandBRAFwild-type patients with an acceptable toxicity profile. Drawing from these considerations, we designed TRIPLETE study aiming at comparing two different chemotherapy backbones (mFOLFOXIRI or mFOLFOX6) in combination with panitumumab in the first-line treatment of patients withRASandBRAFwild-type metastatic colorectal cancer.MethodsThis is a prospective, open-label, multicentre phase III trial in which initially unresectable and previously untreatedRASandBRAFwild-type metastatic colorectal cancer patients are randomised to receive a standard treatment with mFOLFOX6 plus panitumumab or an experimental regimen with modified FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, L-leucovorin 200 mg/m2, 5-fluoruracil 2400 mg/m248-hour continuous infusion) plus panitumumab up to 12 cycles, followed by panitumumab plus 5-fluorouracil and L-leucovorin until disease progression. The primary endpoint is overall response rate according to RECIST 1.1 criteria.DiscussionThe relative benefit of chemotherapy intensification when using an anti-EGFR-based regimen in molecularly selected patients is unknown; TRIPLETE study aims at filling this gap of knowledge. The study is sponsored by the Gruppo Oncologico Nord Ovest Cooperative Group and is currently ongoing at 42 Italian centres.Clinical trial informationNCT03231722.

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Randomized, Open-Label, Phase III Study of a 28-Day Oral Regimen of Eniluracil Plus Fluorouracil Versus Intravenous Fluorouracil Plus Leucovorin as First-Line Therapy in Patients With Metastatic/Advanced Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2002.20.6.1519 ◽

2002 ◽

Vol 20 (6) ◽

pp. 1519-1526 ◽

Cited By ~ 26

Author(s):

Richard L. Schilsky ◽

Jeremey Levin ◽

William H. West ◽

Alfred Wong ◽

Bruce Colwell ◽

...

Keyword(s):

Colorectal Cancer ◽

Advanced Colorectal Cancer ◽

Phase Iii ◽

First Line ◽

Open Label ◽

First Line Therapy ◽

Line Therapy ◽

Open Label Phase ◽

Phase Iii Study ◽

Grade 3

PURPOSE: To compare the efficacy and tolerability of eniluracil (EU)/fluorouracil (5-FU) with that of 5-FU/leucovorin (LV) as first-line therapy for patients with metastatic/advanced colorectal cancer. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study (FUMA3008) conducted in the United States and Canada compared the safety and efficacy of EU/5-FU (11.5 mg/m2/1.15 mg/m2 twice daily for 28 days every 35 days) with that of intravenous 5-FU/LV (425 mg/m2/20 mg/m2 once daily for 5 days every 28 days) in patients with previously untreated metastatic colorectal cancer. Overall survival (OS) was the primary end point. RESULTS: A total of 981 patients were randomized and 964 patients received treatment (485 EU/5FU, 479 5FU/LV). Survival for EU/5-FU was not statistically equivalent (but not statistically inferior) to that for 5-FU/LV (hazard ratio, 0.880; 95% confidence interval [CI], 0.75 to 1.03). Median duration of survival was 13.3 months in the EU/5-FU group and 14.5 months in the 5-FU/LV group. Median duration of progression-free survival for EU/5-FU was statistically inferior to that of the control group (20.0 weeks [95% CI, 19.1 to 20.9 weeks] v 22.7 weeks [95% CI, 18.3 to 24.6 weeks]; P = .01). Both treatments were well tolerated. Diarrhea was the most common nonhematologic toxicity in both groups; treatment-related grade 3 or 4 diarrhea occurred in 19% of patients treated with EU/5-FU and 16% of patients receiving 5-FU/LV (P = .354). Grade 3 or 4 granulocytopenia occurred in 5% of EU/5-FU patients and 47% of 5-FU/LV patients. CONCLUSION: Safety profiles of both treatments were acceptable. Although antitumor activity was observed, EU/5-FU did not meet the protocol-specified statistical criteria for equivalence to 5-FU/LV in terms of OS.

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Phase III study of regorafenib versus placebo as maintenance therapy in RAS wild type metastatic colorectal cancer (RAVELLO trial).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.tps789 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. TPS789-TPS789 ◽

Cited By ~ 1

Author(s):

Erika Martinelli ◽

Teresa Troiani ◽

Filippo Venturini ◽

Andres Cervantes ◽

Jean Yves Douillard ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Maintenance Treatment ◽

Phase Iii ◽

Wild Type ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Wide Range ◽

Phase Iii Study

TPS789 Background: Treatment of metastatic colorectal cancer (mCRC) has improved due to the introduction of more active chemotherapies (CT) and novel targeted agents that have significantly increased response rate (RR), progression free survival (PFS) and overall survival (OS). Recently, CORRECT and CONCUR trials have demonstrated both activity and efficacy of regorafenib, a small multi-kinase inhibitor, as monotherapy in pretreated mCRC. The wide range of action of regorafenib makes it an ideal candidate for monotherapy in earlier disease treatment lines in which different pathways could be involved in the acquisition of resistance. To improve long term efficacy of first line therapy several therapeutic approaches of maintenance treatment have been explored in mCRC. Methods: RAVELLO is an academic randomized, double-blind, placebo-controlled, multi-center, phase III study designed to evaluate efficacy and safety of regorafenib as maintenance treatment after first line therapy. Eligible patients: pathologically confirmed mCRC RAS wild type (KRAS and NRAS genes) treated with a first line fluoropyrimidine-based CT in combination with an anti-EGFR (epidermal growth factor receptor) monoclonal antibody for a minimum of 4 to a maximum of 8 months, with a stratification by response to the first line treatment (complete response/partial response or stable disease). 480 patients will be enrolled and randomly assigned in a 1:1 ratio to receive 160 mg regorafenib or placebo per os, every day for 3 weeks of every 4 weeks cycle, until disease progression or unacceptable toxicity. Primary endpoint is PFS. With a two-tailed alpha error of 0.05, the study will have 90% power to detect a 3-month prolongation of median PFS from randomization (corresponding to a hazard ratio of progression of 0.67 with 6-month median PFS expected in the control arm). Secondary endopoint are OS, safety, and biomarker correlative studies. Currently, one patient has been enrolled and is on treatment. EudraCT number: 2013-005428-41. Clinical trial information: 2013-005428-41.

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