A Phase I, Gene Alteration-based, Open Label, Multicenter Study of Oral Debio 1347 (CH5183284) in Patients With Advanced Solid Malignancies, Whose Tumours Have an Alteration of the FGFR 1, 2 or 3 Genes


Condition: Solid Tumours

Intervention:

  • Drug: Debio1347 (CH5183284)

Purpose: This study is primarily designed to assess the safety and the tolerability of Debio1347 (CH5183284) in patients with advanced solid malignancies, whose tumours have an alteration of the Fibroblast Growth Factor Receptor (FGFR) 1, 2 or 3 genes, for whom standard treatment does not exist or is not indicated. The main objective of Part A is to identify the dose-limiting toxicities (DLTs) and estimate the maximum tolerated dose (MTD) based on the safety and tolerability of Debio1347 orally administered daily to these patients, in order to determine the recommended dose. The main objective of Part B is to evaluate the safety profile at the recommended dose, in a larger cohort of these patients.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01948297

Sponsor: Debiopharm International SA

Primary Outcome Measures:

  • Measure: Part A: Percentage of participants with dose-limiting toxicities (DLTs) from Debio 1347
  • Time Frame: within approximately 18 months
  • Safety Issue:
  • Measure: Part B: Percentage of participants with treatment-emergent Serious Adverse Events (SAEs)
  • Time Frame: within 2 years of starting treatment
  • Safety Issue:
  • Measure: Part B: Percentage of participants with treatment-emergent adverse events (AEs) and laboratory abnormalities
  • Time Frame: within 2 years of starting treatment
  • Safety Issue:
  • Measure: Part B: Severity of treatment-emergent AEs and laboratory abnormalities
  • Time Frame: within 2 years of starting treatment
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Part A: Percentage of participants with treatment-emergent AEs and laboratory abnormalities
  • Time Frame: within 2 years of starting treatment
  • Safety Issue:
  • Measure: Part A: Severity of treatment-emergent AEs and laboratory abnormalities
  • Time Frame: within 2 years of starting treatment
  • Safety Issue:
  • Measure: Part A and Part B: Percentage of participants with treatment discontinuations or modifications due to AEs and laboratory abnormalities
  • Time Frame: within 2 years of starting treatment
  • Safety Issue:
  • Measure: Part A and Part B: Number of participants with change from baseline in vital signs
  • Time Frame: within 2 years of starting treatment
  • Safety Issue:
  • Measure: Part A and Part B: Percentage of participants with tumour response, according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 criteria
  • Time Frame: within 2 years of starting treatment
  • Safety Issue:
  • Measure: Part A and Part B: Number of participants with progression-free survival after treatment initiation
  • Time Frame: within 2 years of starting treatment
  • Safety Issue:
  • Measure: Part A and Part B: Number of participants with changes in ophthalmological exams
  • Time Frame: within 2 years of starting treatment
  • Safety Issue:
  • Measure: Part A and Part B: Maximum concentration (Cmax) of Debio1347 in the pharmacokinetic (PK) subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A and Part B: Time to maximum concentration (tmax) of Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A and Part B: Apparent terminal half-life (t½) of Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A and Part B: Area under the concentration versus time curve from the beginning to a point in time (AUC0-t) for Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A and Part B: Area under the plasma concentration-time curve over the dosing interval (AUCt) for Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A: Area under the plasma concentration-time curve extrapolated to infinity (AUC∞) for Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A and Part B: Apparent terminal elimination rate constant (λz) of Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A and Part B: Mean residence time (MRT) for Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A and Part B: Apparent total body clearance (CL/F) of Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A and Part B: Apparent volume of distribution during the terminal phase (Vz/F) of Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A and Part B: Peak-to-Trough fluctuation (PTF) of Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A and Part B: Average steady-state concentration (Css av) of Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A: Accumulation ratio (RAUC) of Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A: Cmax ratio (RCmax) of Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A: Trough concentration (Ctrough) of Debio1347 in the PK subset
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part A: Estimated relative oral bioavailability of Debio1347
  • Time Frame: after 28 days of continuous dosing
  • Safety Issue:
  • Measure: Part B: Cumulative amount of Debio1347 excreted in urine at steady-state (Ae) in the PK subset
  • Time Frame: on Day 28
  • Safety Issue:
  • Measure: Part B: Percentage of the dose of Debio1347 administered excreted in urine at steady-state (Ae%) in the PK subset
  • Time Frame: on Day 28
  • Safety Issue:
  • Measure: Part B: Renal clearance (CLR) of Debio1347 at steady-state in the PK subset
  • Time Frame: on Day 28
  • Safety Issue:
  • Measure: Part A and Part B: Ctrough of Debio1347 in all participants
  • Time Frame: within 2 years of starting treatment
  • Safety Issue:

Estimated Enrollment: 112

Study Start Date: August 2013

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Meets protocol-specified criteria for qualification and contraception
  • Is willing and able to remain confined in the study unit for the entire duration of each treatment period and comply with 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

Locations:

  • Dana-Farber Cancer Institute
  • Boston Massachusetts 02114 United States
  • Massachusetts General Hospital
  • Boston Massachusetts 02215 United States
  • Memorial Sloan-Kettering Hospital
  • New York New York 10065 United States
  • The University of Texas; MD Anderson Cancer Center
  • Houston Texas 77030-4009 United States
  • Vall d'Hebron University Hospital
  • Barcelona Spain

View trial on ClinicalTrials.gov


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