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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02022098
Recruitment Status : Active, not recruiting
First Posted : December 27, 2013
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
Debiopharm International SA

Tracking Information
First Submitted Date  ICMJE December 13, 2013
First Posted Date  ICMJE December 27, 2013
Last Update Posted Date April 1, 2021
Study Start Date  ICMJE October 2013
Actual Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 19, 2014)
Phase II: Percentage of participants achieving Locoregional Control (LRC) at 18 months from the end of chemo-radiation therapy (CRT) [ Time Frame: within 4 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 20, 2013)
Maximum tolerated dose (MTD) of Debio 1143 in combination with concurrent CRT in patients with LA-SCCHN. [ Time Frame: 18 months ]
Safety profile of Debio 1143 in combination with concurrent CRT
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2016)
  • Phase II: Complete Response Rate (by RECIST version 1.1) at six months after completion of chemo-radiation therapy (CRT) therapy [ Time Frame: within 5 years ]
  • Phase II: Best Overall response rate, Disease Control rate and Response Rate after 10 weeks from the end of CRT [ Time Frame: within 5 years ]
  • Phase II: Best Overall response rate, Disease Control rate and Response Rate after 6 months from the end of CRT [ Time Frame: within 5 years ]
  • Phase II: Locoregional control rate at 6 months and one year after completion of CRT [ Time Frame: within 5 years ]
  • Phase II: Progression free survival rate at one year, 18 months and at 2 years as of initiation of CRT [ Time Frame: within 5 years ]
  • Phase II: Distant relapse rate at six months, one year and 18 months after completion of CRT [ Time Frame: within 5 years ]
  • Phase II: Disease specific survival rate one year and at 2 years as of initiation of CRT [ Time Frame: within 5 years ]
  • Phase II: Overall survival rate at one year and at 2 years as of initiation of CRT [ Time Frame: within 5 years ]
  • Phase II: Number of participants with clinically significant change in vital signs during participation in the trial [ Time Frame: within 5 years ]
  • Phase II: Number of participants with Serious Adverse Events [ Time Frame: within 5 years ]
  • Phase II: Number of participants with Adverse Events (AEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: within 5 years ]
    Categories: at 1 year, at 2 years
  • Phase II: Number of participants with treatment changes due to AEs [ Time Frame: within 5 years ]
    Categories: Treatment discontinuation, Treatment modification
Original Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2013)
Anti-tumour activity of the recommended dose of Debio 1143 in combination with concurrent CRT in the study population [ Time Frame: 18 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: December 20, 2013)
  • PK of Debio 1143 and cisplatin when administered in combination with radiation therapy, and explore the potential for drug-drug interactions of Debio 1143 in combination with cisplatin [ Time Frame: 18 months ]
    Pharmacokinetic parameters (Cmax, AUC, tmax,CL/F, Vss/F, ) of Debio 1143 alone and in combination withcisplatin and radiotherapy.
  • Pharmacodynamic biomarkers of Debio 1143 activity in combination with concurrent CRT [ Time Frame: 18 months ]
    cIAP1 in PBMCs serum cytokeratin 18, IL-8, MCP-1 and TNF-alpha
 
Descriptive Information
Brief Title  ICMJE Debio 1143-201 Dose-finding and Efficacy Phase I/II Trial
Official Title  ICMJE 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.
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Squamous Cell Carcinoma of the Head and Neck
Intervention  ICMJE
  • 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 Name: Concomitant Chemotherapy
  • Radiation: Radiotherapy
    Standard fraction radiotherapy to the primary tumour will be delivered daily for 5 days per week over 7 weeks.
    Other Name: Concomitant Radiotherapy
  • Drug: Debio 1143
    Debio 1143 solution
  • Drug: Placebo
    Matching placebo solution
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: Cisplatin
    • Radiation: Radiotherapy
    • Drug: Debio 1143
  • 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).
    Interventions:
    • Drug: Cisplatin
    • Radiation: Radiotherapy
    • Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 27, 2018)
110
Original Estimated Enrollment  ICMJE
 (submitted: December 20, 2013)
22
Estimated Study Completion Date  ICMJE July 2022
Actual Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02022098
Other Study ID Numbers  ICMJE Debio 1143-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Debiopharm International SA
Study Sponsor  ICMJE Debiopharm International SA
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Debiopharm International SA
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP