scholarly journals TRIPLETE: a randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectableRASandBRAFwild-type metastatic colorectal cancer

ESMO Open ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. e000403 ◽  
Author(s):  
Beatrice Borelli ◽  
Roberto Moretto ◽  
Sara Lonardi ◽  
Andrea Bonetti ◽  
Carlotta Antoniotti ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Initial Therapy ◽  
Phase Iii ◽  
Wild Type ◽  
Open Label ◽  
Multicentre Phase ◽  
Phase Iii Study ◽  
Colorectal Cancer Patients ◽  
To Receive

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.

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

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. TPS3648-TPS3648
Author(s):  
Benoist Chibaudel ◽  
Christophe Tournigand ◽  
Franck Bonnetain ◽  
Marine Hug de larauze ◽  
Armand De Gramont ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Iii ◽  
Wild Type ◽  
Open Label ◽  
Line Therapy ◽  
Open Label Phase ◽  
Phase Iii Study ◽  
Therapy Trial

scholarly journals STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Benoist Chibaudel ◽  
Franck Bonnetain ◽  
Christophe Tournigand ◽  
Marine Hug de Larauze ◽  
Armand de Gramont ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Iii ◽  
Wild Type ◽  
Open Label ◽  
Phase Iii Study

scholarly journals Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study

2021 ◽  
Author(s):  
Takeshi Kato ◽  
Yoshinori Kagawa ◽  
Yasutoshi Kuboki ◽  
Makio Gamoh ◽  
Yoshito Komatsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Therapeutic Option ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Wild Type ◽  
Open Label ◽  
Safety And Efficacy ◽  
Multicentre Phase

Abstract Background We aimed to assess the safety and efficacy of combination treatment with panitumumab plus trifluridine/tipiracil (FTD/TPI) in patients with wild-type RAS metastatic colorectal cancer (mCRC) who were refractory/intolerant to standard therapies other than anti-epidermal growth factor receptor therapy. Methods APOLLON was an open-label, multicentre, phase 1/2 trial. In the phase 1 part, 3 + 3 de-escalation design was used to investigate the recommended phase 2 dose (RP2D); all patients in the phase 2 part received the RP2D. The primary endpoint was investigator-assessed progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and safety. Results Fifty-six patients were enrolled (phase 1, n = 7; phase 2, n = 49) at 25 Japanese centres. No dose-limiting toxicities were observed in patients receiving panitumumab (6 mg/kg every 2 weeks) plus FTD/TPI (35 mg/m2 twice daily; days 1–5 and 8–12 in a 28-day cycle), which became RP2D. PFS rate at 6 months was 33.3% (90% confidence interval [CI] 22.8–45.3). Median PFS, OS, ORR, DCR, and TTF were 5.8 months (95% CI 4.5–6.5), 14.1 months (95% CI 12.2–19.3), 37.0% (95% CI 24.3–51.3), 81.5% (95% CI 68.6–90.8), and 5.8 months (95% CI 4.29–6.21), respectively. Neutrophil count decreased (47.3%) was the most common Grade 3/4 treatment-emergent adverse event. No treatment-related deaths occurred. Conclusion Panitumumab plus FTD/TPI exhibited favourable anti-tumour activity with a manageable safety profile and may be a therapeutic option for pre-treated mCRC patients.

MABp1 to improve clinical outcomes of patients with symptomatic refractory metastatic colorectal cancer patients: Per-protocol population analysis of phase III study (PT026).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3530-3530
Author(s):  
Lucjan Wyrwicz ◽  
Mark P. Saunders ◽  
Thierry Andre ◽  
Tomasz Sarosiek ◽  
Radim Nemecek ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Endpoint ◽  
Population Analysis ◽  
Interleukin 1 ◽  
Phase Iii ◽  
Protocol Population ◽  
Toxic Agents ◽  
Phase Iii Study ◽  
Colorectal Cancer Patients

3530 Background: Refractory metastatic colorectal cancer (mCRC) patients derive minimal benefit from further exposure to toxic agents. MABp1 is an anti-interleukin 1 alpha antibody that is shown to prolong survival (NCT01767857) and improves outcomes when assessed with a primary endpoint based on a constellation of objective and patient self-reported measures (NCT02138422) (Hickish T. et al Lancet Oncology 2017). In the latter study, clinically advanced patients were enrolled (symptomatic, ECOG 1,2), and 18% of patients progressed prior to reaching the endpoint assessments. Here we present the outcomes in per-protocol population (PP), those patients completing week 8 assessments. Methods: 309 patients randomized 2:1 to receive MABp1 versus placebo. Patients were ECOG 1-2, with mCRC refractory to chemotherapy, any degree of weight loss, and cancer-associated symptoms. The composite primary endpoint assessed the rate of patients achieving stabilization or improvement in lean body mass (LBM) and two of three symptom measures (pain, fatigue, appetite loss) from screening to the week 8 assessment. The study was designed for placebo cross-over, thus OS analysis for MABp1 vs placebo was not possible. Results: 57 patients (38 MABp1 [18%] and 19 placebo [19%]) discontinued study prior to the week 8 assessment due to disease progression, including 17 (8%) and 11 (11%) deaths in MABp1 and placebo respectively. 62% of placebo patients received MABp1 after 8 weeks. 252 patients, 40% in MABp1 (68/169) vs 23% in placebo (19/83) met the primary endpoint (p = 0.003). 139 patients were available for PP survival analysis (90 MABp1 vs 49 Placebo). Median OS of those achieving the primary endpoint was 11.7 months vs 5.7 months for those that did not (HR 0.39; p < 0.0001). Radiographic stable disease was improved (42% vs 12%; p < 0.001) and incidence of SAEs (6% vs 15%; p = 0.11) reduced in those achieving the primary endpoint. Conclusions: Achieving the primary endpoint was associated with improvement in outcomes, RECIST stabilization, SAEs and survival. Further study should confirm the effect of MABp1 on survival in this population. Clinical trial information: NCT02138422.

scholarly journals A Phase III open-label, randomized, multicenter study of imprime pgg in combination with cetuximab in patients with kras wild type metastatic colorectal cancer

2014 ◽  
Vol 2 (Suppl 3) ◽  
pp. P71 ◽  
Author(s):  
Jeffrey A Meyerhardt ◽  
Michele M Grady ◽  
Jamie N Lowe ◽  
Michele A Gargano ◽  
Richard D Huhn ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Multicenter Study ◽  
Phase Iii ◽  
Wild Type ◽  
Open Label
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