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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| Debio1347 (CH5183284) | CH5183284 | Part 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
| Name | Type | Description | Interventions |
|---|
| Part A | Experimental | Adaptive doses of Debio1347 (CH5183284) - (10 mg to 210 mg/day) until the recommended dose (RD) is determined. | |
| Part B | Experimental | Participants with various tumours receive Debio1347 (CH5183284) orally at the recommended dose established during Part A. | |
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: | Terminated |
| Lead Sponsor: | Debiopharm International SA |
Last Updated
September 9, 2020
