NCT01948297TerminatedPhase 1
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
Debiopharm International SA8 sites in 5 countries77 target enrollmentStarted: August 2013Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Debiopharm International SA
- Enrollment
- 77
- Locations
- 8
- Primary Endpoint
- Part B: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
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:
- •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
Arms & Interventions
Part A
Experimental
Adaptive doses of Debio1347 (CH5183284) - (10 mg to 210 mg/day) until the recommended dose (RD) is determined.
Intervention: Debio1347 (CH5183284) (Drug)
Part B
Experimental
Participants with various tumours receive Debio1347 (CH5183284) orally at the recommended dose established during Part A.
Intervention: Debio1347 (CH5183284) (Drug)
Outcomes
Primary Outcomes
Part B: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
Time Frame: within 2 years of starting treatment
Part A: Percentage of Participants With Dose-Limiting Toxicities (DLTs) From Debio 1347
Time Frame: within approximately 18 months
Part B: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Time Frame: within 2 years of starting treatment
Part B: Severity of Treatment-Emergent AEs
Time Frame: 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
Time Frame: within 2 years of starting treatment
Categories: NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4 severity criteria
Secondary Outcomes
- 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)
- Part A: Severity of Laboratory Abnormalities(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)(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)(within 2 years of starting treatment)
- Part A and Part B: Progression-Free Survival Rate After Treatment Initiation(within 2 years of starting treatment)
- Part A and Part B: Number of Participants With Changes in Ophthalmological Exams(within 2 years of starting treatment)
- 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)
- Part A and Part B: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters(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: 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)
- 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)
Investigators
Study Sites (8)
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