Clinical Trial - NCT01948297

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

Recruiting

Sponsor: Debiopharm International SA

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT01948297

Protocol Info

Short Description: Phase I of Debio 1347 in ASTs With Fibroblast Growth Factor Receptor (FGFR) Alterations
Long Description: 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 Fibroblast Growth Factor Receptor (FGFR) 1, 2 or 3 Genes
MGH Status: Open
Sponsor: Debiopharm
Disease Program: Phase I

Next Steps


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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.
Condition Title Intervention Phase
Solid Tumours Debio1347 (CH5183284) Phase 1
Study Type Interventional
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

Primary Outcome Measures

Part A: Percentage of Participants With Dose-Limiting Toxicities (DLTs) From Debio 1347 [Time Frame: within approximately 18 months] [Designated as safety issue: ]

Part B: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) [Time Frame: within 2 years of starting treatment] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Part B: Severity of Treatment-Emergent AEs [Time Frame: within 2 years of starting treatment] [Designated as safety issue: ]

Part B: Severity of Laboratory Abnormalities [Time Frame: within 2 years of starting treatment] [Designated as safety issue: ]


Secondary Outcome Measures

Part A: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) [Time Frame: within 2 years of starting treatment] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Part A: Severity of Treatment-Emergent AEs [Time Frame: within 2 years of starting treatment] [Designated as safety issue: ]

Part A: Severity of Laboratory Abnormalities [Time Frame: within 2 years of starting treatment] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Part A and Part B: Number of Participants With Change From Baseline in Blood Pressure (BP) [Time Frame: within 2 years of starting treatment] [Designated as safety issue: ]

Part A and Part B: Number of Participants With Change From Baseline in Pulse Rate [Time Frame: within 2 years of starting treatment] [Designated as safety issue: ]

Part A and Part B: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters [Time Frame: within 2 years of starting treatment] [Designated as safety issue: ]

Part A and Part B: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) [Time Frame: within 2 years of starting treatment] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Part A and Part B: Progression-Free Survival Rate After Treatment Initiation [Time Frame: within 2 years of starting treatment] [Designated as safety issue: ]

Part A and Part B: Number of Participants With Changes in Ophthalmological Exams [Time Frame: within 2 years of starting treatment] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Part B: Area Under Concentration-Time Curve (AUC), Following Repeated-Dose Administration of Debio 1347 in the PK Subset [Time Frame: Day 28] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Part B: Maximum Observed Concentration (Cmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [Time Frame: Day 28] [Designated as safety issue: ]

Part B: Time of Maximum Concentration (tmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [Time Frame: Day 28] [Designated as safety issue: ]

Part B: Apparent Terminal Half-Life (t1/2) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [Time Frame: Day 28] [Designated as safety issue: ]

Part B: Mean Residence Time (MRT) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [Time Frame: Day 28] [Designated as safety issue: ]

Part B: Apparent clearance (CL/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [Time Frame: Day 28] [Designated as safety issue: ]

Part B: Apparent Volume of Distribution (Vz/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [Time Frame: Day 28] [Designated as safety issue: ]

Part B: Peak-to-Trough Fluctuation (PTF) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [Time Frame: Day 28] [Designated as safety issue: ]

Part B: Renal Clearance (CLR) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [Time Frame: Day 28] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Estimated Enrollment: 118
Study Start Date: August 2013
Estimated Study Completion Date: March 2020
Estimated Primary Completion Date: March 2020
Arms Assigned Interventions

Experimental:Part A

Adaptive doses of Debio1347 (CH5183284) - (10 mg to 210 mg/day) until the recommended dose (RD) is determined.
Drug:Debio1347 (CH5183284)
Debio1347 (CH5183284) tablets for oral administration

Experimental:Part B

Participants with various tumours receive Debio1347 (CH5183284) orally at the recommended dose established during Part A.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01948297

Locations

  • United States, Massachusetts
    • Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02114
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02215
  • United States, New York
    • Memorial Sloan-Kettering Hospital New York, New York, United States, 10065
  • United States, Texas
    • The University of Texas; MD Anderson Cancer Center Houston, Texas, United States, 77030-4009
  • Korea, Republic of,
    • Seoul National University Hospital Seoul, , Korea, Republic of, 03080
  • Singapore,
    • National Cancer Center Singapore Singapore, , Singapore, 169610
  • Spain,
    • Vall d'Hebron University Hospital Barcelona, , Spain,
  • Taiwan,
    • Taipei Medical University Hospital Taipei, , Taiwan, 11031

Sponsors and Collaborators

Debiopharm International SA

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT01948297
Other Study ID Numbers: 2013-000316-19
Study First Received:
Last Updated:
Health Authority:

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019