Debio 1143-201 Dose-finding and Efficacy Phase I/II Trial

NCT02022098 | Completed DMC

• 1 other identifier: Debio 1143-201
• Study Type: interventional
• Target: 144
• Locations: 2 countries
• Sites: 19

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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• Phase II: Percentage of participants achieving Locoregional Control (LRC) at 18 months from the end of chemo-radiation therapy (CRT)

  within 4 years

Secondary Outcomes (14)

• Phase II: Complete Response Rate (by RECIST version 1.1) at six months after completion of chemo-radiation therapy (CRT) therapy

  within 5 years

• Phase II: Best Overall response rate, Disease Control rate and Response Rate after 10 weeks from the end of CRT

  within 5 years

• Phase II: Best Overall response rate, Disease Control rate and Response Rate after 6 months from the end of CRT

  within 5 years

• Phase II: Locoregional control rate at 6 months and one year after completion of CRT

  within 5 years

• Phase II: Progression free survival rate at one year, 18 months and at 2 years as of initiation of CRT

  within 5 years

Study Arms (2)

Debio 1143

EXPERIMENTAL

In addition to Cisplatin and Radiotherapy, Debio 1143 in solution form will be administered orally or by feeding tube (while fasting) daily for 14 days every three weeks (on days 1-14, 22-35 and 43-56).

Drug: Cisplatin; Radiation: Radiotherapy; Drug: Debio 1143

Placebo

PLACEBO COMPARATOR

In addition to Cisplatin and Radiotherapy, matching placebo in solution form will be administered orally or by feeding tube (while fasting) daily for 14 days every three weeks (on days 1-14, 22-35 and 43-56).

Drug: Cisplatin; Radiation: Radiotherapy; Drug: Placebo

Interventions

Cisplatin DRUG

A total of three cycles of cisplatin will be administered in a 1-hour IV infusion on days 2, 23 and 44. Cisplatin will be administered 0.5 hours after Debio 1143.

Also known as: Concomitant Chemotherapy

Debio 1143; Placebo

Radiotherapy RADIATION

Standard fraction radiotherapy to the primary tumour will be delivered daily for 5 days per week over 7 weeks.

Also known as: Concomitant Radiotherapy

Debio 1143; Placebo

Debio 1143 DRUG

Debio 1143 solution

Debio 1143

Placebo DRUG

Matching placebo solution

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (19)

Centre Hospitalier de Bretagne Sud - HÔPITAL DU SCORFF

Lorient, BP 2233, 56322, France

Location

C.H.U. Sud Amiens

Amiens, 80054, France

Location

Institut Sainte-Catherine

Avignon, 84918, France

Location

Centre Jean Perrin

Clermont-Ferrand, BP 392, France

Location

CHU Grenoble

Grenoble, BP 217, France

Location

CHD Vendée

La Roche-sur-Yon, F- 85925, France

Location

Centre Guillaume le Conquérant

Le Havre, 76600, France

Location

Centre Jean Bernard

Le Mans, France

Location

Hôpital Nord Franche-Comté

Montbéliard, 25200, France

Location

ICM - Val D'Aurelle

Montpellier, 34298, France

Location

Institut Curie

Paris, 75248, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Institut de Cancérologie de l'Ouest (ICO) René Gauducheau

Saint-Herblain, BP 217, France

Location

Institut de Cancérologie Lucien Neuwirth (ICLN)

Saint-Priest-en-Jarez, BP 60008, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

L'Institut de Cancérologie de Lorraine (ICL) Alexis Vautrin

Vandœuvre-lès-Nancy, CS 30519, France

Location

Institut Gustave Roussy

Villejuif, 94000, France

Location

Inselspital Bern, Universitätsklinik für Radio-Onkologie, Freiburgstrasse 4

Bern, 3010, Switzerland

Location

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, 1011, Switzerland

Location

Related Publications (4)

• Vugmeyster Y, Ravula A, Rouits E, Diderichsen PM, Kleijn HJ, Koenig A, Wang X, Schroeder A, Goteti K, Venkatakrishnan K. Model-Informed Selection of the Recommended Phase III Dose of the Inhibitor of Apoptosis Protein Inhibitor, Xevinapant, in Combination with Cisplatin and Concurrent Radiotherapy in Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck. Clin Pharmacol Ther. 2024 Jan;115(1):52-61. doi: 10.1002/cpt.3065. Epub 2023 Oct 23.

  PMID: 37777832 DERIVED

• Tao Y, Sun XS, Pointreau Y, Tourneau CL, Sire C, Gollmer K, Crompton P, Bourhis J. Long-term results from a clinical study of xevinapant plus chemoradiotherapy in people with high-risk locally advanced squamous cell carcinoma of the head and neck: a plain language summary. Future Oncol. 2023 Aug;19(26):1769-1776. doi: 10.2217/fon-2023-0322. Epub 2023 Jul 13.

  PMID: 37439181 DERIVED

• Tao Y, Sun XS, Pointreau Y, Le Tourneau C, Sire C, Kaminsky MC, Coutte A, Alfonsi M, Calderon B, 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, Damstrup L, Crompton P, Ennaji A, Gollmer K, Nauwelaerts H, Bourhis J. Extended follow-up of a phase 2 trial of xevinapant plus chemoradiotherapy in high-risk locally advanced squamous cell carcinoma of the head and neck: a randomised clinical trial. Eur J Cancer. 2023 Apr;183:24-37. doi: 10.1016/j.ejca.2022.12.015. Epub 2023 Jan 9.

  PMID: 36796234 DERIVED

• 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.

  PMID: 32758455 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cisplatin; Radiotherapy; N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamide

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2013
• First Posted: December 27, 2013
• Study Start: October 1, 2013
• Primary Completion: July 1, 2020
• Study Completion: April 28, 2022
• Last Updated: June 23, 2022

Record last verified: 2022-06

Locations

FR (17); CH (2)