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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: Cisplatin
* Radiation: Radiotherapy
* Drug: Debio 1143
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Debio 1143<br>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<br>* 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.<br>* Other names: Concomitant Chemotherapy;Radiation: Radiotherapy<br>* Standard fraction radiotherapy to the primary tumour will be delivered daily for 5 days per week over 7 weeks.<br>* Other names: Concomitant Radiotherapy;Drug: Debio 1143<br>* Debio 1143 solution<br>|
| Placebo Comparator: Placebo<br>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<br>* 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.<br>* Other names: Concomitant Chemotherapy;Radiation: Radiotherapy<br>* Standard fraction radiotherapy to the primary tumour will be delivered daily for 5 days per week over 7 weeks.<br>* Other names: Concomitant Radiotherapy;Drug: Placebo<br>* Matching placebo solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |