Clinical Trials /

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

NCT01948297

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: Debio 1347-101
  • SECONDARY ID: 2013-000316-19
  • NCT ID: NCT01948297

Conditions

  • Solid Tumours

Interventions

DrugSynonymsArms
Debio1347 (CH5183284)CH5183284Part A

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.

Trial Arms

NameTypeDescriptionInterventions
Part AExperimentalAdaptive doses of Debio1347 (CH5183284) - (10 mg to 210 mg/day) until the recommended dose (RD) is determined.
  • Debio1347 (CH5183284)
Part BExperimentalParticipants with various tumours receive Debio1347 (CH5183284) orally at the recommended dose established during Part A.
  • Debio1347 (CH5183284)

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

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:
Description:Categories: NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4 severity criteria

Secondary Outcome Measures

Measure:Part A: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
Time Frame:within 2 years of starting treatment
Safety Issue:
Description:
Measure:Part A: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Time Frame:within 2 years of starting treatment
Safety Issue:
Description:
Measure:Part A: Severity of Treatment-Emergent AEs
Time Frame:within 2 years of starting treatment
Safety Issue:
Description:Categories: NCI-CTCAE version 4 severity criteria
Measure:Part A: Severity of Laboratory Abnormalities
Time Frame:within 2 years of starting treatment
Safety Issue:
Description:Categories: NCI-CTCAE version 4 severity criteria
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:
Description:
Measure:Part A and Part B: Number of Participants With Change From Baseline in Blood Pressure (BP)
Time Frame:within 2 years of starting treatment
Safety Issue:
Description: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).
Measure:Part A and Part B: Number of Participants With Change From Baseline in Pulse Rate
Time Frame:within 2 years of starting treatment
Safety Issue:
Description:Number of participants with change of more than 20 beats per minute from baseline will be reported.
Measure:Part A and Part B: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters
Time Frame:within 2 years of starting treatment
Safety Issue:
Description:ECG parameters will include PR, RR, QRS, QTcB and QTcF intervals.
Measure:Part A and Part B: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Time Frame:within 2 years of starting treatment
Safety Issue:
Description:
Measure:Part A and Part B: Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Time Frame:within 2 years of starting treatment
Safety Issue:
Description:
Measure:Part A: Number 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:
Description:Includes: Best overall response, disease control, tumour size
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)
Time Frame:within 2 years of starting treatment
Safety Issue:
Description:Includes: Best overall response, disease control, tumour size
Measure:Part A and Part B: Progression-Free Survival Rate After Treatment Initiation
Time Frame:within 2 years of starting treatment
Safety Issue:
Description:Categories: overall, 6 months, 1 year, 2 years
Measure:Part A and Part B: Number of Participants With Changes in Ophthalmological Exams
Time Frame:within 2 years of starting treatment
Safety Issue:
Description:Opthalmological exams includes visual acuity testing, slit-lamp ophthalmoscopy and indirect ophthalmoscopy.
Measure:Part A: Area Under Concentration-Time Curve (AUC) Following Single- and Repeated-Dose Administration of Debio 1347
Time Frame: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
Safety Issue:
Description:
Measure:Part A: Concentration at the end of a Dosing Interval (Ctrough) Following Single- and Repeated-Dose Administration of Debio 1347
Time Frame: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
Safety Issue:
Description:
Measure:Part A: Maximum Observed Concentration (Cmax) Following Single- and Repeated-Dose Administration of Debio 1347
Time Frame: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
Safety Issue:
Description:
Measure:Part A: Time of Maximum Concentration (tmax) Following Single- and Repeated-Dose Administration of Debio 1347
Time Frame: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
Safety Issue:
Description:
Measure:Part A: Apparent Terminal Half-Life (t1/2) Following Single- and Repeated-Dose Administration of Debio 1347
Time Frame: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
Safety Issue:
Description:
Measure:Part A: Mean Residence Time (MRT) Following Single- and Repeated-Dose Administration of Debio 1347
Time Frame: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
Safety Issue:
Description:
Measure:Part A: Apparent Clearance (CL/F) Following Single- and Repeated-Dose Administration of Debio 1347
Time Frame: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
Safety Issue:
Description:
Measure:Part A: Apparent Volume of Distribution (Vz/F) Following Single- and Repeated-Dose Administration of Debio 1347
Time Frame: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
Safety Issue:
Description:
Measure:Part A: Accumulation Ratios (RAC) Following Single- and Repeated-Dose Administration of Debio 1347
Time Frame: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
Safety Issue:
Description:
Measure:Part A: Linearity Index (LI) Following Single- and Repeated-Dose Administration of Debio 1347
Time Frame: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
Safety Issue:
Description:
Measure:Part A: Peak-to-Trough fluctuation (PTF) Following Single- and Repeated-Dose Administration of Debio 1347
Time Frame: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
Safety Issue:
Description:
Measure:Part B: Area Under Concentration-Time Curve (AUC), Following Repeated-Dose Administration of Debio 1347 in the PK Subset
Time Frame:Day 28
Safety Issue:
Description:
Measure:Part B: Concentration at the end of a Dosing Interval (Ctrough) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
Time Frame:Day 28
Safety Issue:
Description:
Measure:Part B: Maximum Observed Concentration (Cmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
Time Frame:Day 28
Safety Issue:
Description:
Measure:Part B: Time of Maximum Concentration (tmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
Time Frame:Day 28
Safety Issue:
Description:
Measure:Part B: Apparent Terminal Half-Life (t1/2) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
Time Frame:Day 28
Safety Issue:
Description:
Measure:Part B: Mean Residence Time (MRT) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
Time Frame:Day 28
Safety Issue:
Description:
Measure:Part B: Apparent clearance (CL/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
Time Frame:Day 28
Safety Issue:
Description:
Measure:Part B: Apparent Volume of Distribution (Vz/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
Time Frame:Day 28
Safety Issue:
Description:
Measure:Part B: Peak-to-Trough Fluctuation (PTF) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
Time Frame:Day 28
Safety Issue:
Description:
Measure:Part B: Renal Clearance (CLR) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
Time Frame:Day 28
Safety Issue:
Description:
Measure:Part B: Percentage of the Dose Excreted in Urine (Ae%) Following Repeated-Dose Administration of Debio 1347 in the PK Subset
Time Frame:Day 28
Safety Issue:
Description:
Measure:Part B: Ctrough in all Participants
Time Frame:Day 8, Day 15, Day 22 of Cycle 1, and Day 1 of Cycle 2 and Cycle 3
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Debiopharm International SA

Last Updated