The FLOTILLA Study: Providing Continued Access to The Study Medicines Encorafenib and Binimetinib for Participants in Prior Clinical Trials

Official title

ENCORAFENIB/BINIMETINIB MASTER PROTOCOL: AN OPEN-LABEL CONTINUATION STUDY FOR PARTICIPANTS CONTINUING FROM ENCORAFENIB/BINIMETINIB CLINICAL STUDIES

Overview

The purpose of this clinical trial (called the FLOTILLA study) is to give continued access to the study medicines, as well as safety follow-up, for participants in prior clinical trials of encorafenib and/or binimetinib. All participants who took part in earlier encorafenib and/or binimetinib studies may participate the FLOTILLA study if they are still benefiting from the use of the study medicines. This will be determined by the study doctor. People may not participate in the FLOTILLA study if they have not enrolled in a prior study of encorafenib or binimetinib. Participants that had enrolled but had stopped receiving the study treatment in a prior study cannot enrolled in this study. Participants in the FLOTILLA study will receive encorafenib and/or binimetinib at the same dose and frequency as in their prior study, for up to about 5 years.

Detailed description

This is an open-label, continuation study for participants receiving study intervention(s) in an encorafenib/binimetinib Parent Study. The study is being conducted under a Master Protocol for Encorafenib/Binimetinib Continuation Sub-Studies with an individual encorafenib/binimetinib continuation sub-study protocol for each eligible Parent Study. Approximately 75 participants from potentially qualifying Parent Studies will be included in this Encorafenib/Binimetinib Continuation study.

This continuation study includes multiple sub-study protocols to allow participants from each of the following parent studies: C4211001 - NCT01320085; C4211003 - NCT01849874; C4221003 - NCT03864042; C4221005 - NCT01543698; C4221006 - NCT03911869; C4221009 - NCT02928224; C4221010 - NCT01436656; C4221013 - NCT02159066; ANCHOR-CRC - NCT03693170

Interventions

• Drug Binimetinib only treatment
  Binimetinib will be administered at the same dose level (15 mg to 45 mg) as that received in the Parent Studies C4211001 and C4211003 with water irrespective of food, continuously, starting on Day 1.
• Drug Encorafenib only Treatment
  Encorafenib will be self-administered at the same dose level as that received in the C4221010 Parent Study.
• Drug Encorafenib & Binimetinib Treatment
  Encorafenib will be administered on a 300 mg QD schedule and binimetinib will be administered on a 45 mg BID schedule, both orally as a flat fixed dose. Cetuximab will be administered at either 400 mg/m2 or 500 mg/m2 IV every 2 weeks on Days 1 and 15 of every cycle.
• Drug Treatment of Encorafenib & Binimetinib & Ribociclib
  Encorafenib capsule and ribociclib capsules or tablets will be co-administered orally QD with binimetinib tablets BID. The study drugs will be administered as a flat-fixed dose, and not by body weight or body surface area.
• Drug Treatment of Encorafenib & Binimetinib & Cetuximab
  Encorafenib will be administered on a 300 mg QD schedule and binimetinib will be administered on a 45 mg BID schedule, both orally as a flat fixed dose. Cetuximab will be administered at either 400 mg/m2 or 500 mg/m2 IV every 2 weeks on Days 1 and 15 of every cycle.

Primary outcome measures

• Number of participants with adverse events leading to permanent discontinuation of study intervention [Time frame: Baseline up to approximately 5 years]
• Number serious adverse events reported for all participants [Time frame: Baseline up to approximately 5 years]

Eligibility criteria

Inclusion criteria

• Any participant who is receiving study intervention and deriving clinical benefit (as determined by the principal investigator) in an encorafenib/binimetinib Parent Study, with no ongoing NCI CTCAE version 4.03 Grade ≥3 or intolerable Grade 2 AEs considered to be related to study treatment.
• Participants must agree to follow the reproductive criteria as outlined in the applicable Encorafenib/Binimetinib Continuation Sub-Study Protocol.

Exclusion criteria

• Any medical reason that, in the opinion of the investigator or sponsor, precludes the participant from inclusion in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 18 centers

• St. Joseph's Hospital and Medical Center — Phoenix
• St. Joseph's Hospital and Medical Center — Phoenix
• Emory University Hospital Midtown — Atlanta
• Emory University Hospital — Atlanta
• Investigational Drug Service Emory University Clinic — Atlanta
• Winship Cancer Institute of Emory University — Atlanta
• Massachusetts General Hospital — Boston
• HealthPartners Cancer Research Center — Saint Paul
• … and 10 more centers

Spain · 12 centers

• CHUAC-Hospital Teresa Herrera — A Coruña
• Institut Català d'Oncologia (ICO) - Badalona — Badalona
• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital Clinic de Barcelona — Barcelona
• Hospital Clínic de Barcelona — Barcelona
• Hospital Universitario Arnau de Vilanova de Lleida — Lleida
• Hospital Universitario Puerta de Hierro Majadahonda — Majadahonda
• Hospital Universitari Vall d'Hebron — Barcelona
• … and 4 more centers

Italy · 7 centers

• Instituto Tumori Giovanni Paolo II — Bari
• Istituto Nazionale Tumori Regina Elena — Rome
• Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia — Candiolo
• Istituto Oncologico Veneto IRCCS — Padova
• IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola — Bologna
• Istituto Europeo di Oncologia IRCCS — Milan
• Istituto Nazionale Tumori IRCCS Fondazione Pascale — Naples

Brazil · 5 centers

• Liga Norte Riograndense Contra o Câncer — Natal
• ONCOSITE - Centro de Pesquisa Clinica em Oncologia — Ijuí
• Fundação Pio XII - Hospital de Câncer de Barretos — Barretos
• BP - A Beneficencia Portuguesa de São Paulo — São Paulo
• Real e Benemerita Associacao Portuguesa de Beneficencia — São Paulo

Canada · 3 centers

• University Health Network — Toronto
• Princess Margaret Cancer Centre — Toronto
• Jewish General Hospital — Montreal

Germany · 3 centers

• Universitaetsklinikum Tuebingen — Tübingen
• Otto-von-Guericke-Universitat Magdeburg — Magdeburg
• Charité Universitaetsmedizin Berlin - Campus Mitte — Berlin

Netherlands · 3 centers

• Radboudumc — Nijmegen
• Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL) — Amsterdam
• Isala, locatie Zwolle — Zwolle

Russia · 3 centers

• N.N.Petrov Research Institute of Oncology — Saint Petersburg
• Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF — Moscow
• N.N.Petrov Research Institute of Oncology — Saint Petersburg

South Korea · 3 centers

• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Samsung Medical Center — Seoul

France · 2 centers

• Hopital Claude Huriez - CHU de Lille — Lille
• Gustave Roussy — Villejuif

Portugal · 2 centers

• Instituto Português de Oncologia de Lisboa Francisco Gentil — Lisbon
• Instituto Português de Oncologia do Porto Francisco Gentil, EPE — Porto

Australia · 1 center

• Peter MacCallum Cancer Centre — Melbourne

Czechia · 1 center

• Vseobecna fakultni nemocnice v Praze — Prague

Hungary · 1 center

• Debreceni Egyetem Klinikai Kozpont — Debrecen

Israel · 1 center

• Rambam Health Care Campus — Haifa

Slovakia · 1 center

• Narodny onkologicky ustav — Bratislava

United Kingdom · 1 center

• Lancashire Teaching Hospitals NHS Foundation Trust - Royal Preston Hospital — Preston

Identifiers

NCT: NCT05203172 · C4221026 · FLOTILLA · 2023-509408-13-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗