Debio 1347-101 Phase I Trial in Advanced Solid Tumours With Fibroblast Growth Factor Receptor (FGFR) Alterations
- Conditions
- Solid Tumours
- Interventions
- Drug: Debio1347 (CH5183284)
- Registration Number
- NCT01948297
- Lead Sponsor
- Debiopharm International SA
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 77
Not provided
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B Debio1347 (CH5183284) Participants with various tumours receive Debio1347 (CH5183284) orally at the recommended dose established during Part A. Part A Debio1347 (CH5183284) Adaptive doses of Debio1347 (CH5183284) - (10 mg to 210 mg/day) until the recommended dose (RD) is determined.
- Primary Outcome Measures
Name Time Method Part B: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) within 2 years of starting treatment Part A: Percentage of Participants With Dose-Limiting Toxicities (DLTs) From Debio 1347 within approximately 18 months 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 within 2 years of starting treatment Categories: NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4 severity criteria
Part B: Severity of Laboratory Abnormalities within 2 years of starting treatment Categories: NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4 severity criteria
- Secondary Outcome Measures
Name Time Method 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 within 2 years of starting treatment Categories: NCI-CTCAE version 4 severity criteria
Part A: Severity of Laboratory Abnormalities within 2 years of starting treatment Categories: NCI-CTCAE version 4 severity criteria
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) within 2 years of starting treatment 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).
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) within 2 years of starting treatment Includes: Best overall response, disease control, tumour size
Part A and Part B: Progression-Free Survival Rate After Treatment Initiation within 2 years of starting treatment Categories: overall, 6 months, 1 year, 2 years
Part A and Part B: Number of Participants With Changes in Ophthalmological Exams within 2 years of starting treatment Opthalmological exams includes visual acuity testing, slit-lamp ophthalmoscopy and indirect ophthalmoscopy.
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 and Part B: Number of Participants With Change From Baseline in Pulse Rate within 2 years of starting treatment Number of participants with change of more than 20 beats per minute from baseline will be reported.
Part A and Part B: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters within 2 years of starting treatment ECG parameters will include PR, RR, QRS, QTcB and QTcF intervals.
Part A and Part B: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) 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 within 2 years of starting treatment Includes: Best overall response, disease control, tumour size
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: 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 A and Part B: Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) 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: 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: 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 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 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: Percentage of the Dose Excreted in Urine (Ae%) 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: Renal Clearance (CLR) 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
Trial Locations
- Locations (8)
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Memorial Sloan-Kettering Hospital
🇺🇸New York, New York, United States
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
The University of Texas; MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
National Cancer Center Singapore
🇸🇬Singapore, Singapore
Vall d'Hebron University Hospital
🇪🇸Barcelona, Spain
Taipei Medical University Hospital
🇨🇳Taipei, Taiwan
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States