Clinical trial NCT02022098: Debio 1143-201 Dose-finding and Efficacy Phase I/II Trial
Official title: A Phase I/II Randomized Study to Determine the Maximum Tolerated Dose, Safety, Pharmacokinetics and Antitumor Activity of Debio 1143 Combined With Concurrent Chemo-Radiation Therapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Squamous Cell Carcinoma of the Head and Neck
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2013-12-27
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The use of multiple drugs in a single clinical trial or as a therapeutic strategy has become common, particularly in the treatment of cancer. Because traditional trials are designed to evaluate one agent at a time, the evaluation of therapies in combination requires specialized trial designs. In place of the traditional separate phase I and II trials, this trial uses a single phase I/II clinical trial to evaluate simultaneously the safety and efficacy of combination dose levels, and select the optimal combination dose.

Therefore, this is a two part trial of Debio 1143 combined with concurrent cisplatin and radiotherapy (CRT) in participants with previously untreated stage III, IVa or IVb head and neck cancer. The trial begins with an initial period of dose escalation (Phase I) to investigate the maximum tolerated dose (MTD) of Debio 1143 that can safely be given in combination with CRT.

Using the MTD determined in the Phase I portion, the randomized phase II trial in 94 participants compares Debio 1143 to placebo, both with concomitant CRT. The aim is to evaluate the efficacy and safety of Debio 1143.


Eligibility criteria: Inclusion Criteria:

* Meets protocol-specified criteria for qualification and contraception
* Is willing and able to comply with study procedures and restrictions related to food, drink and medications
* Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures

Exclusion Criteria:

* Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters
* Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

  1. the safety or well-being of the participant or study staff;
  2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding);
  3. the analysis of results

Primary outcomes:
measure: Phase II: Percentage of participants achieving Locoregional Control (LRC) at 18 months from the end of chemo-radiation therapy (CRT)
timeFrame: within 4 years
Secondary outcomes:
measure: Phase II: Complete Response Rate (by RECIST version 1.1) at six months after completion of chemo-radiation therapy (CRT) therapy
timeFrame: within 5 years
measure: Phase II: Best Overall response rate, Disease Control rate and Response Rate after 10 weeks from the end of CRT
timeFrame: within 5 years
measure: Phase II: Best Overall response rate, Disease Control rate and Response Rate after 6 months from the end of CRT
timeFrame: within 5 years
measure: Phase II: Locoregional control rate at 6 months and one year after completion of CRT
timeFrame: within 5 years
measure: Phase II: Progression free survival rate at one year, 18 months and at 2 years as of initiation of CRT
timeFrame: within 5 years
measure: Phase II: Distant relapse rate at six months, one year and 18 months after completion of CRT
timeFrame: within 5 years
measure: Phase II: Disease specific survival rate one year and at 2 years as of initiation of CRT
timeFrame: within 5 years
measure: Phase II: Overall survival rate at one year and at 2 years as of initiation of CRT
timeFrame: within 5 years
measure: Phase II: Number of participants with clinically significant change in vital signs during participation in the trial
timeFrame: within 5 years
measure: Phase II: Number of participants with Serious Adverse Events
timeFrame: within 5 years
measure: Phase II: Number of participants with Adverse Events (AEs)
timeFrame: within 5 years
measure: Phase II: Number of participants with Laboratory Abnormalities
timeFrame: within 5 years
measure: Phase II: Number of participants with Late Toxicity as of initiation of CRT
timeFrame: within 5 years
measure: Phase II: Number of participants with treatment changes due to AEs
timeFrame: within 5 years
Other outcomes:
Locations:
city: Lorient
country: France
facility: Centre Hospitalier de Bretagne Sud - HÔPITAL DU SCORFF
state: Bp 2233
city: Amiens
country: France
facility: C.H.U. Sud Amiens
city: Avignon Cedex 9
country: France
facility: Institut Sainte-Catherine
city: Clermont-Ferrand Cedex 01
country: France
facility: Centre Jean Perrin
city: Grenoble
country: France
facility: CHU Grenoble
city: La Roche Sur Yon cedex 9
country: France
facility: CHD Vendée
city: Le Havre
country: France
facility: Centre Guillaume le Conquérant
city: Le Mans
country: France
facility: Centre Jean Bernard
city: Montbéliard
country: France
facility: Hôpital Nord Franche-Comté
city: Montpellier
country: France
facility: ICM - Val D'Aurelle
city: Paris
country: France
facility: Institut Curie
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Herblain
country: France
facility: Institut de Cancérologie de l'Ouest (ICO) René Gauducheau
city: Saint-Priest en Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth (ICLN)
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Vandoeuvre-lès-Nancy
country: France
facility: L'Institut de Cancérologie de Lorraine (ICL) Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Bern
country: Switzerland
facility: Inselspital Bern, Universitätsklinik für Radio-Onkologie, Freiburgstrasse 4
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
Study officials:
References:
citation: Sun XS, Tao Y, Le Tourneau C, Pointreau Y, Sire C, Kaminsky MC, Coutte A, Alfonsi M, Boisselier P, Martin L, Miroir J, Ramee JF, Delord JP, Clatot F, Rolland F, Villa J, Magne N, Elicin O, Gherga E, Nguyen F, Lafond C, Bera G, Calugaru V, Geoffrois L, Chauffert B, Zubel A, Zanna C, Brienza S, Crompton P, Rouits E, Gollmer K, Szyldergemajn S, Bourhis J. Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study. Lancet Oncol. 2020 Sep;21(9):1173-1187. doi: 10.1016/S1470-2045(20)30327-2. Epub 2020 Aug 3.