Clinical trial NCT01948297: Debio 1347-101 Phase I Trial in Advanced Solid Tumours With Fibroblast Growth Factor Receptor (FGFR) Alterations
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumours
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2013-09-23
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Part A: Percentage of Participants With Dose-Limiting Toxicities (DLTs) From Debio 1347
timeFrame: within approximately 18 months
measure: Part B: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: within 2 years of starting treatment
measure: Part B: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
timeFrame: within 2 years of starting treatment
measure: Part B: Severity of Treatment-Emergent AEs
timeFrame: within 2 years of starting treatment
measure: Part B: Severity of Laboratory Abnormalities
timeFrame: within 2 years of starting treatment
Secondary outcomes:
measure: Part A: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: within 2 years of starting treatment
measure: Part A: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
timeFrame: within 2 years of starting treatment
measure: Part A: Severity of Treatment-Emergent AEs
timeFrame: within 2 years of starting treatment
measure: Part A: Severity of Laboratory Abnormalities
timeFrame: within 2 years of starting treatment
measure: Part A and Part B: Percentage of Participants With Treatment Discontinuations or Modifications due to AEs and Laboratory Abnormalities
timeFrame: within 2 years of starting treatment
measure: Part A and Part B: Number of Participants With Change From Baseline in Blood Pressure (BP)
timeFrame: within 2 years of starting treatment
measure: Part A and Part B: Number of Participants With Change From Baseline in Pulse Rate
timeFrame: within 2 years of starting treatment
measure: Part A and Part B: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters
timeFrame: within 2 years of starting treatment
measure: Part A and Part B: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
timeFrame: within 2 years of starting treatment
measure: Part A and Part B: Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
timeFrame: within 2 years of starting treatment
measure: Part A: Number of Participants With Tumour Response, According to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 Criteria
timeFrame: within 2 years of starting treatment
measure: 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)
timeFrame: within 2 years of starting treatment
measure: Part A and Part B: Progression-Free Survival Rate After Treatment Initiation
timeFrame: within 2 years of starting treatment
measure: Part A and Part B: Number of Participants With Changes in Ophthalmological Exams
timeFrame: within 2 years of starting treatment
measure: Part A: Area Under Concentration-Time Curve (AUC) Following Single- and Repeated-Dose Administration of Debio 1347
timeFrame: 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
measure: Part A: Concentration at the end of a Dosing Interval (Ctrough) Following Single- and Repeated-Dose Administration of Debio 1347
timeFrame: 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
measure: Part A: Maximum Observed Concentration (Cmax) Following Single- and Repeated-Dose Administration of Debio 1347
timeFrame: 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
measure: Part A: Time of Maximum Concentration (tmax) Following Single- and Repeated-Dose Administration of Debio 1347
timeFrame: 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
measure: Part A: Apparent Terminal Half-Life (t1/2) Following Single- and Repeated-Dose Administration of Debio 1347
timeFrame: 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
measure: Part A: Mean Residence Time (MRT) Following Single- and Repeated-Dose Administration of Debio 1347
timeFrame: 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
measure: Part A: Apparent Clearance (CL/F) Following Single- and Repeated-Dose Administration of Debio 1347
timeFrame: 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
measure: Part A: Apparent Volume of Distribution (Vz/F) Following Single- and Repeated-Dose Administration of Debio 1347
timeFrame: 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
measure: Part A: Accumulation Ratios (RAC) Following Single- and Repeated-Dose Administration of Debio 1347
timeFrame: 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
measure: Part A: Linearity Index (LI) Following Single- and Repeated-Dose Administration of Debio 1347
timeFrame: 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
measure: Part A: Peak-to-Trough fluctuation (PTF) Following Single- and Repeated-Dose Administration of Debio 1347
timeFrame: 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
measure: Part B: Area Under Concentration-Time Curve (AUC), Following Repeated-Dose Administration of Debio 1347 in the PK Subset
timeFrame: Day 28
measure: Part B: Concentration at the end of a Dosing Interval (Ctrough) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
timeFrame: Day 28
measure: Part B: Maximum Observed Concentration (Cmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
timeFrame: Day 28
measure: Part B: Time of Maximum Concentration (tmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
timeFrame: Day 28
measure: Part B: Apparent Terminal Half-Life (t1/2) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
timeFrame: Day 28
measure: Part B: Mean Residence Time (MRT) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
timeFrame: Day 28
measure: Part B: Apparent clearance (CL/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
timeFrame: Day 28
measure: Part B: Apparent Volume of Distribution (Vz/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
timeFrame: Day 28
measure: Part B: Peak-to-Trough Fluctuation (PTF) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
timeFrame: Day 28
measure: Part B: Renal Clearance (CLR) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
timeFrame: Day 28
measure: Part B: Percentage of the Dose Excreted in Urine (Ae%) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
timeFrame: Day 28
measure: Part B: Ctrough in all Participants
timeFrame: Day 8, Day 15, Day 22 of Cycle 1, and Day 1 of Cycle 2 and Cycle 3
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Hospital
state: New York
city: Houston
country: United States
facility: The University of Texas; MD Anderson Cancer Center
state: Texas
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Center Singapore
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
Study officials:
References: