Debio 1347-101 Phase I Trial in Advanced Solid Tumours With Fibroblast Growth Factor Receptor (FGFR) Alterations

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

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 Overview

• Status: Terminated
• Conditions: Solid Tumours
• Intervention / Treatment: Drug: Debio1347 (CH5183284)

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Center Singapore
• Spain
  • Barcelona, Spain
    • Vall d'Hebron University Hospital
• Taiwan
  • Taipei, Taiwan, 11031
    • Taipei Medical University Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02114
      • Dana-Farber Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Hospital
  • Texas
    • Houston, Texas, United States, 77030-4009
      • The University of Texas; MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part A; Adaptive doses of Debio1347 (CH5183284) - (10 mg to 210 mg/day) until the recommended dose (RD) is determined.	Drug: Debio1347 (CH5183284); Debio1347 (CH5183284) tablets for oral administration; Other Names: CH5183284
EXPERIMENTAL: Part B; Participants with various tumours receive Debio1347 (CH5183284) orally at the recommended dose established during Part A.	Drug: Debio1347 (CH5183284); Debio1347 (CH5183284) tablets for oral administration; Other Names: CH5183284

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Percentage of Participants With Dose-Limiting Toxicities (DLTs) From Debio 1347		within approximately 18 months
Part B: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)		within 2 years of starting treatment
Part B: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment		within 2 years of starting treatment
Part B: Severity of Treatment-Emergent AEs	Categories: NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4 severity criteria	within 2 years of starting treatment
Part B: Severity of Laboratory Abnormalities	Categories: NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4 severity criteria	within 2 years of starting treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)		within 2 years of starting treatment
Part A: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment		within 2 years of starting treatment
Part A: Severity of Treatment-Emergent AEs	Categories: NCI-CTCAE version 4 severity criteria	within 2 years of starting treatment
Part A: Severity of Laboratory Abnormalities	Categories: NCI-CTCAE version 4 severity criteria	within 2 years of starting treatment
Part A and Part B: Percentage of Participants With Treatment Discontinuations or Modifications due to AEs and Laboratory Abnormalities		within 2 years of starting treatment
Part A and Part B: Number of Participants With Change From Baseline in Blood Pressure (BP)	Change in BP will be evaluation based on three criteria- "Change to Low" (decrease from pre-treatment > 20 millimeter of mercury [mmHg]), "No change" (change from pre-treatment within ± 20 mmHg) and "Change to High" (increase from pre-treatment > 20 mmHg).	within 2 years of starting treatment
Part A and Part B: Number of Participants With Change From Baseline in Pulse Rate	Number of participants with change of more than 20 beats per minute from baseline will be reported.	within 2 years of starting treatment
Part A and Part B: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters	ECG parameters will include PR, RR, QRS, QTcB and QTcF intervals.	within 2 years of starting treatment
Part A and Part B: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)		within 2 years of starting treatment
Part A and Part B: Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)		within 2 years of starting treatment
Part A: Number of Participants With Tumour Response, According to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 Criteria	Includes: Best overall response, disease control, tumour size	within 2 years of starting treatment
Part B: Number of Participants With Tumour Response, According to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 Citeria or Response Assessment in Neuro-Oncology (RANO) (for glioblastoma participants)	Includes: Best overall response, disease control, tumour size	within 2 years of starting treatment
Part A and Part B: Progression-Free Survival Rate After Treatment Initiation	Categories: overall, 6 months, 1 year, 2 years	within 2 years of starting treatment
Part A and Part B: Number of Participants With Changes in Ophthalmological Exams	Opthalmological exams includes visual acuity testing, slit-lamp ophthalmoscopy and indirect ophthalmoscopy.	within 2 years of starting treatment
Part A: Area Under Concentration-Time Curve (AUC) Following Single- and Repeated-Dose Administration of Debio 1347		Day -9, Day -2, Day 28; Ctrough on Day 8, Day 15, Day 22 of Cycle 1, and on Day 1 of Cycle 2 and Cycle 3
Part A: Concentration at the end of a Dosing Interval (Ctrough) Following Single- and Repeated-Dose Administration of Debio 1347		Day -9, Day -2, Day 28; Ctrough on Day 8, Day 15, Day 22 of Cycle 1, and on Day 1 of Cycle 2 and Cycle 3
Part A: Maximum Observed Concentration (Cmax) Following Single- and Repeated-Dose Administration of Debio 1347		Day -9, Day -2, Day 28; Ctrough on Day 8, Day 15, Day 22 of Cycle 1, and on Day 1 of Cycle 2 and Cycle 3
Part A: Time of Maximum Concentration (tmax) Following Single- and Repeated-Dose Administration of Debio 1347		Day -9, Day -2, Day 28; Ctrough on Day 8, Day 15, Day 22 of Cycle 1, and on Day 1 of Cycle 2 and Cycle 3
Part A: Apparent Terminal Half-Life (t1/2) Following Single- and Repeated-Dose Administration of Debio 1347		Day -9, Day -2, Day 28; Ctrough on Day 8, Day 15, Day 22 of Cycle 1, and on Day 1 of Cycle 2 and Cycle 3
Part A: Mean Residence Time (MRT) Following Single- and Repeated-Dose Administration of Debio 1347		Day -9, Day -2, Day 28; Ctrough on Day 8, Day 15, Day 22 of Cycle 1, and on Day 1 of Cycle 2 and Cycle 3
Part A: Apparent Clearance (CL/F) Following Single- and Repeated-Dose Administration of Debio 1347		Day -9, Day -2, Day 28; Ctrough on Day 8, Day 15, Day 22 of Cycle 1, and on Day 1 of Cycle 2 and Cycle 3
Part A: Apparent Volume of Distribution (Vz/F) Following Single- and Repeated-Dose Administration of Debio 1347		Day -9, Day -2, Day 28; Ctrough on Day 8, Day 15, Day 22 of Cycle 1, and on Day 1 of Cycle 2 and Cycle 3
Part A: Accumulation Ratios (RAC) Following Single- and Repeated-Dose Administration of Debio 1347		Day -9, Day -2, Day 28; Ctrough on Day 8, Day 15, Day 22 of Cycle 1, and on Day 1 of Cycle 2 and Cycle 3
Part A: Linearity Index (LI) Following Single- and Repeated-Dose Administration of Debio 1347		Day -9, Day -2, Day 28; Ctrough on Day 8, Day 15, Day 22 of Cycle 1, and on Day 1 of Cycle 2 and Cycle 3
Part A: Peak-to-Trough fluctuation (PTF) Following Single- and Repeated-Dose Administration of Debio 1347		Day -9, Day -2, Day 28; Ctrough on Day 8, Day 15, Day 22 of Cycle 1, and on Day 1 of Cycle 2 and Cycle 3
Part B: Area Under Concentration-Time Curve (AUC), Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Part B: Concentration at the end of a Dosing Interval (Ctrough) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Part B: Maximum Observed Concentration (Cmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Part B: Time of Maximum Concentration (tmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Part B: Apparent Terminal Half-Life (t1/2) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Part B: Mean Residence Time (MRT) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Part B: Apparent clearance (CL/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Part B: Apparent Volume of Distribution (Vz/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Part B: Peak-to-Trough Fluctuation (PTF) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Part B: Renal Clearance (CLR) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Part B: Percentage of the Dose Excreted in Urine (Ae%) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Part B: Ctrough in all Participants		Day 8, Day 15, Day 22 of Cycle 1, and Day 1 of Cycle 2 and Cycle 3

Collaborators and Investigators

• Sponsor: Debiopharm International SA

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): June 26, 2020
• Study Completion (ACTUAL): June 26, 2020

Study Registration Dates

• First Submitted: August 26, 2013
• First Submitted That Met QC Criteria: September 18, 2013
• First Posted (ESTIMATE): September 23, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: Debio 1347-101; 2013-000316-19 (EUDRACT_NUMBER)