Squamous Cell Carcinoma of the Head and Neck
Conditions
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.
Interventions
DRUGCisplatin
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.
RADIATIONRadiotherapy
Standard fraction radiotherapy to the primary tumour will be delivered daily for 5 days per week over 7 weeks.
DRUGDebio 1143
Debio 1143 solution
DRUGPlacebo
Matching placebo solution
Sponsors
Debiopharm International SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: Complete Response Rate (by RECIST version 1.1) at six months after completion of chemo-radiation therapy (CRT) therapy | 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) | within 5 years | Categories will be based on severity graded according to NCI-CTCAE version 4 criteria |
| Phase II: Number of participants with Laboratory Abnormalities | within 5 years | Categories will be based on severity graded according to NCI-CTCAE version 4 criteria |
| Phase II: Number of participants with Late Toxicity as of initiation of CRT | within 5 years | Categories: at 1 year, at 2 years |
| Phase II: Number of participants with treatment changes due to AEs | within 5 years | Categories: Treatment discontinuation, Treatment modification |
| Phase II: Overall survival rate at one year and at 2 years as of initiation of CRT | within 5 years | — |
Countries
France, Switzerland
Outcome results
None listed