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

Squamous Cell Carcinoma of the Head and Neck Clinical 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02022098
• Other study ID #: Debio 1143-201
• Status: Completed
• Phase: N/A
• Start date: October 2013
• Est. completion date: April 28, 2022

Study information

• Verified date: June 2022
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: April 28, 2022
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck

Intervention

Drug:
• 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.

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

Drug:
• Debio 1143
Debio 1143 solution
• Placebo
Matching placebo solution

Locations

Country	Name	City	State
France	C.H.U. Sud Amiens	Amiens
France	Institut Sainte-Catherine	Avignon Cedex 9
France	Centre Jean Perrin	Clermont-Ferrand Cedex 01
France	CHU Grenoble	Grenoble
France	CHD Vendée	La Roche Sur Yon cedex 9
France	Centre Guillaume le Conquérant	Le Havre
France	Centre Jean Bernard	Le Mans
France	Centre Hospitalier de Bretagne Sud - HÔPITAL DU SCORFF	Lorient	Bp 2233
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	Vandoeuvre-lès-Nancy
France	Institut Gustave Roussy	Villejuif
Switzerland	Inselspital Bern, Universitätsklinik für Radio-Onkologie, Freiburgstrasse 4	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Countries where clinical trial is conducted

France,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase II: Percentage of participants achieving Locoregional Control (LRC) at 18 months from the end of chemo-radiation therapy (CRT)		within 4 years
Secondary	Phase II: Complete Response Rate (by RECIST version 1.1) at six months after completion of chemo-radiation therapy (CRT) therapy		within 5 years
Secondary	Phase II: Best Overall response rate, Disease Control rate and Response Rate after 10 weeks from the end of CRT		within 5 years
Secondary	Phase II: Best Overall response rate, Disease Control rate and Response Rate after 6 months from the end of CRT		within 5 years
Secondary	Phase II: Locoregional control rate at 6 months and one year after completion of CRT		within 5 years
Secondary	Phase II: Progression free survival rate at one year, 18 months and at 2 years as of initiation of CRT		within 5 years
Secondary	Phase II: Distant relapse rate at six months, one year and 18 months after completion of CRT		within 5 years
Secondary	Phase II: Disease specific survival rate one year and at 2 years as of initiation of CRT		within 5 years
Secondary	Phase II: Overall survival rate at one year and at 2 years as of initiation of CRT		within 5 years
Secondary	Phase II: Number of participants with clinically significant change in vital signs during participation in the trial		within 5 years
Secondary	Phase II: Number of participants with Serious Adverse Events		within 5 years
Secondary	Phase II: Number of participants with Adverse Events (AEs)	Categories will be based on severity graded according to NCI-CTCAE version 4 criteria	within 5 years
Secondary	Phase II: Number of participants with Laboratory Abnormalities	Categories will be based on severity graded according to NCI-CTCAE version 4 criteria	within 5 years
Secondary	Phase II: Number of participants with Late Toxicity as of initiation of CRT	Categories: at 1 year, at 2 years	within 5 years
Secondary	Phase II: Number of participants with treatment changes due to AEs	Categories: Treatment discontinuation, Treatment modification	within 5 years