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

Solid Tumours Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT01948297
• Other study ID #: Debio 1347-101
• Secondary ID: 2013-000316-19
• Status: Terminated
• Phase: Phase 1
• Start date: August 2013
• Est. completion date: June 26, 2020

Study information

• Verified date: September 2020
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 77
• Est. completion date: June 26, 2020
• Est. primary completion date: June 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Solid Tumours

Intervention

Drug:
• Debio1347 (CH5183284)
Debio1347 (CH5183284) tablets for oral administration

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul
Singapore	National Cancer Center Singapore	Singapore
Spain	Vall d'Hebron University Hospital	Barcelona
Taiwan	Taipei Medical University Hospital	Taipei
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University of Texas; MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan-Kettering Hospital	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Singapore,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Percentage of Participants With Dose-Limiting Toxicities (DLTs) From Debio 1347		within approximately 18 months
Primary	Part B: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)		within 2 years of starting treatment
Primary	Part B: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment		within 2 years of starting treatment
Primary	Part B: Severity of Treatment-Emergent AEs	Categories: NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4 severity criteria	within 2 years of starting treatment
Primary	Part B: Severity of Laboratory Abnormalities	Categories: NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4 severity criteria	within 2 years of starting treatment
Secondary	Part A: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)		within 2 years of starting treatment
Secondary	Part A: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment		within 2 years of starting treatment
Secondary	Part A: Severity of Treatment-Emergent AEs	Categories: NCI-CTCAE version 4 severity criteria	within 2 years of starting treatment
Secondary	Part A: Severity of Laboratory Abnormalities	Categories: NCI-CTCAE version 4 severity criteria	within 2 years of starting treatment
Secondary	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
Secondary	Part A and Part B: Number of Participants With Change From Baseline in Blood Pressure (BP)	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).	within 2 years of starting treatment
Secondary	Part A and Part B: Number of Participants With Change From Baseline in Pulse Rate	Number of participants with change of more than 20 beats per minute from baseline will be reported.	within 2 years of starting treatment
Secondary	Part A and Part B: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters	ECG parameters will include PR, RR, QRS, QTcB and QTcF intervals.	within 2 years of starting treatment
Secondary	Part A and Part B: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)		within 2 years of starting treatment
Secondary	Part A and Part B: Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)		within 2 years of starting treatment
Secondary	Part A: Number of Participants With Tumour Response, According to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 Criteria	Includes: Best overall response, disease control, tumour size	within 2 years of starting treatment
Secondary	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)	Includes: Best overall response, disease control, tumour size	within 2 years of starting treatment
Secondary	Part A and Part B: Progression-Free Survival Rate After Treatment Initiation	Categories: overall, 6 months, 1 year, 2 years	within 2 years of starting treatment
Secondary	Part A and Part B: Number of Participants With Changes in Ophthalmological Exams	Opthalmological exams includes visual acuity testing, slit-lamp ophthalmoscopy and indirect ophthalmoscopy.	within 2 years of starting treatment
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part B: Area Under Concentration-Time Curve (AUC), Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Secondary	Part B: Concentration at the end of a Dosing Interval (Ctrough) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Secondary	Part B: Maximum Observed Concentration (Cmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Secondary	Part B: Time of Maximum Concentration (tmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Secondary	Part B: Apparent Terminal Half-Life (t1/2) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Secondary	Part B: Mean Residence Time (MRT) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Secondary	Part B: Apparent clearance (CL/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Secondary	Part B: Apparent Volume of Distribution (Vz/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Secondary	Part B: Peak-to-Trough Fluctuation (PTF) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Secondary	Part B: Renal Clearance (CLR) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Secondary	Part B: Percentage of the Dose Excreted in Urine (Ae%) Following Repeated-Dose Administration of Debio 1347 in the PK Subset		Day 28
Secondary	Part B: Ctrough in all Participants		Day 8, Day 15, Day 22 of Cycle 1, and Day 1 of Cycle 2 and Cycle 3

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