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

NCT ID: NCT02022098

Last Updated: 2022-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2022-04-28

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Debio 1143

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).

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: 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.

Radiotherapy

Intervention Type: RADIATION

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

Debio 1143

Intervention Type: DRUG

Debio 1143 solution

Placebo

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).

Group Type: PLACEBO_COMPARATOR

Cisplatin

Intervention Type: 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.

Radiotherapy

Intervention Type: RADIATION

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

Placebo

Intervention Type: DRUG

Matching placebo solution

Interventions

Cisplatin

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.

Intervention Type: DRUG

Radiotherapy

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

Intervention Type: RADIATION

Debio 1143

Debio 1143 solution

Intervention Type: DRUG

Placebo

Matching placebo solution

Intervention Type: DRUG

Other Intervention Names

Concomitant Chemotherapy; Concomitant Radiotherapy

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Debiopharm International SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Centre Hospitalier de Bretagne Sud - HÔPITAL DU SCORFF

Lorient, BP 2233, France

C.H.U. Sud Amiens

Amiens, , France

Institut Sainte-Catherine

Avignon, , France

Centre Jean Perrin

Clermont-Ferrand, , France

CHU Grenoble

Grenoble, , France

CHD Vendée

La Roche-sur-Yon, , France

Centre Guillaume le Conquérant

Le Havre, , France

Centre Jean Bernard

Le Mans, , France

Hôpital Nord Franche-Comté

Montbéliard, , France

ICM - Val D'Aurelle

Montpellier, , France

Institut Curie

Paris, , France

Centre Henri Becquerel

Rouen, , France

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

Saint-Herblain, , France

Institut de Cancérologie Lucien Neuwirth (ICLN)

Saint-Priest-en-Jarez, , France

Institut Claudius Regaud

Toulouse, , France

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

Vandœuvre-lès-Nancy, , France

Institut Gustave Roussy

Villejuif, , France

Inselspital Bern, Universitätsklinik für Radio-Onkologie, Freiburgstrasse 4

Bern, , Switzerland

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, , Switzerland

Countries

France; Switzerland

References

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.

Reference Type: DERIVED

PMID: 37777832 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37439181 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36796234 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32758455 (View on PubMed)

Other Identifiers

Debio 1143-201

Identifier Type: -

Identifier Source: org_study_id