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

• ClinicalTrials.gov Identifier: NCT02022098
• Recruitment Status: Completed
• First Posted: December 27, 2013
• Last Update Posted: June 23, 2022
• Sponsor: Debiopharm International SA
• Information provided by (Responsible Party): Debiopharm International SA

Tracking Information

• First Submitted Date: December 13, 2013
• First Posted Date: December 27, 2013
• Last Update Posted Date: June 23, 2022
• Actual Study Start Date: October 2013
• Actual Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: Debio 1143-201 Dose-finding and Efficacy Phase I/II 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.

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: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: 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.
  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

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 22, 2022): 144
• Original Estimated Enrollment (submitted: December 20, 2013): 22
• Actual Study Completion Date: April 28, 2022
• Actual Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Switzerland

Administrative Information

• NCT Number: NCT02022098
• Other Study ID Numbers: Debio 1143-201
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Debiopharm International SA
• Original Responsible Party: Same as current
• Current Study Sponsor: Debiopharm International SA
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Debiopharm International SA
• Verification Date: June 2022