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

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.

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.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of the Head and Neck
• Intervention / Treatment: Drug: Cisplatin; Radiation: Radiotherapy; Drug: Debio 1143; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • C.H.U. Sud Amiens
  • Avignon Cedex 9, France, 84918
    • Institut Sainte-Catherine
  • Clermont-Ferrand Cedex 01, France, BP 392
    • Centre Jean Perrin
  • Grenoble, France, BP 217
    • CHU Grenoble
  • La Roche Sur Yon cedex 9, France, F- 85925
    • CHD Vendee
  • Le Havre, France, 76600
    • Centre Guillaume Le Conquerant
  • Le Mans, France
    • Centre Jean Bernard
  • Montbéliard, France, 25200
    • Hôpital Nord Franche-Comté
  • Montpellier, France, 34298
    • ICM - Val d'Aurelle
  • Paris, France, 75248
    • Institut Curie
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Saint-Herblain, France, BP 217
    • Institut de Cancérologie de l'Ouest (ICO) René Gauducheau
  • Saint-Priest en Jarez, France, BP 60008
    • Institut de Cancérologie Lucien Neuwirth (ICLN)
  • Toulouse, France, 31052
    • Institut Claudius Regaud
  • Vandoeuvre-lès-Nancy, France, CS 30519
    • L'Institut de Cancérologie de Lorraine (ICL) Alexis Vautrin
  • Villejuif, France, 94000
    • Institut Gustave Roussy
  • Bp 2233
    • Lorient, Bp 2233, France, 56322
      • Centre Hospitalier de Bretagne Sud - Hopital du Scorff
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern, Universitätsklinik für Radio-Onkologie, Freiburgstrasse 4
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois (CHUV)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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).	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.; Other Names: Concomitant Chemotherapy; Radiation: Radiotherapy; Standard fraction radiotherapy to the primary tumour will be delivered daily for 5 days per week over 7 weeks.; Other Names: Concomitant Radiotherapy; Drug: Debio 1143; Debio 1143 solution
PLACEBO_COMPARATOR: 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).	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.; Other Names: Concomitant Chemotherapy; Radiation: Radiotherapy; Standard fraction radiotherapy to the primary tumour will be delivered daily for 5 days per week over 7 weeks.; Other Names: Concomitant Radiotherapy; Drug: Placebo; Matching placebo solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase II: Percentage of participants achieving Locoregional Control (LRC) at 18 months from the end of chemo-radiation therapy (CRT)	within 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Phase II: Distant relapse rate at six months, one year and 18 months after completion of CRT		within 5 years
Phase II: Disease specific survival rate one year and at 2 years as of initiation of CRT		within 5 years
Phase II: Overall survival rate at one year and at 2 years as of initiation of CRT		within 5 years
Phase II: Number of participants with clinically significant change in vital signs during participation in the trial		within 5 years
Phase II: Number of participants with Serious Adverse Events		within 5 years
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
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
Phase II: Number of participants with Late Toxicity as of initiation of CRT	Categories: at 1 year, at 2 years	within 5 years
Phase II: Number of participants with treatment changes due to AEs	Categories: Treatment discontinuation, Treatment modification	within 5 years

Collaborators and Investigators

• Sponsor: Debiopharm International SA

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2013
• Primary Completion (ACTUAL): July 1, 2020
• Study Completion (ACTUAL): April 28, 2022

Study Registration Dates

• First Submitted: December 13, 2013
• First Submitted That Met QC Criteria: December 20, 2013
• First Posted (ESTIMATE): December 27, 2013

Study Record Updates

• Last Update Posted (ACTUAL): June 23, 2022
• Last Update Submitted That Met QC Criteria: June 22, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: Debio 1143-201