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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by Debiopharm International SA
Sponsor:
Information provided by (Responsible Party):
Debiopharm International SA
ClinicalTrials.gov Identifier:
NCT01948297
First received: August 26, 2013
Last updated: June 10, 2015
Last verified: June 2015
  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 Intervention Phase
Solid Tumours
Drug: Debio1347 (CH5183284)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Debiopharm International SA:

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: No ]
  • Part B: Percentage of participants with treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: within 2 years of starting treatment ] [ Designated as safety issue: No ]
  • Part B: Percentage of participants with treatment-emergent adverse events (AEs) and laboratory abnormalities [ Time Frame: within 2 years of starting treatment ] [ Designated as safety issue: No ]
  • Part B: Severity of treatment-emergent AEs and laboratory abnormalities [ Time Frame: within 2 years of starting treatment ] [ Designated as safety issue: No ]
    Categories: NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4 severity criteria


Secondary Outcome Measures:
  • Part A: Percentage of participants with treatment-emergent AEs and laboratory abnormalities [ Time Frame: within 2 years of starting treatment ] [ Designated as safety issue: No ]
  • Part A: Severity of treatment-emergent AEs and laboratory abnormalities [ Time Frame: within 2 years of starting treatment ] [ Designated as safety issue: No ]
    Categories: NCI-CTCAE version 4 severity criteria

  • 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: No ]
  • Part A and Part B: Number of participants with change from baseline in vital signs [ Time Frame: within 2 years of starting treatment ] [ Designated as safety issue: No ]
    Categories: Electrocardiogram (ECG), Left ventricular ejection fraction (LVEF) and Eastern Cooperative Oncology Group Performance Status (ECOG PS)

  • Part A and Part B: Percentage 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: No ]
    Categories: Overall response, disease control, tumour size

  • Part A and Part B: Number of participants with progression-free survival after treatment initiation [ Time Frame: within 2 years of starting treatment ] [ Designated as safety issue: No ]
    Categories: overall, 6 months, 1 year, 2 years

  • 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: No ]
  • Part A and Part B: Maximum concentration (Cmax) of Debio1347 in the pharmacokinetic (PK) subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A and Part B: Time to maximum concentration (tmax) of Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A and Part B: Apparent terminal half-life (t½) of Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A and Part B: Area under the concentration versus time curve from the beginning to a point in time (AUC0-t) for Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A and Part B: Area under the plasma concentration-time curve over the dosing interval (AUCt) for Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A: Area under the plasma concentration-time curve extrapolated to infinity (AUC∞) for Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A and Part B: Apparent terminal elimination rate constant (λz) of Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A and Part B: Mean residence time (MRT) for Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A and Part B: Apparent total body clearance (CL/F) of Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A and Part B: Apparent volume of distribution during the terminal phase (Vz/F) of Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A and Part B: Peak-to-Trough fluctuation (PTF) of Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A and Part B: Average steady-state concentration (Css av) of Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A: Accumulation ratio (RAUC) of Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A: Cmax ratio (RCmax) of Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A: Trough concentration (Ctrough) of Debio1347 in the PK subset [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
  • Part A: Estimated relative oral bioavailability of Debio1347 [ Time Frame: after 28 days of continuous dosing ] [ Designated as safety issue: No ]
    Categories: Tablet, Capsule

  • Part B: Cumulative amount of Debio1347 excreted in urine at steady-state (Ae) in the PK subset [ Time Frame: on Day 28 ] [ Designated as safety issue: No ]
  • Part B: Percentage of the dose of Debio1347 administered excreted in urine at steady-state (Ae%) in the PK subset [ Time Frame: on Day 28 ] [ Designated as safety issue: No ]
  • Part B: Renal clearance (CLR) of Debio1347 at steady-state in the PK subset [ Time Frame: on Day 28 ] [ Designated as safety issue: No ]
  • Part A and Part B: Ctrough of Debio1347 in all participants [ Time Frame: within 2 years of starting treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 112
Study Start Date: August 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
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) capsules or tablets for oral administration
Other Name: CH5183284
Experimental: Part B
Participants with various tumours receive Debio1347 (CH5183284) orally at the recommended dose established during Part A.
Drug: Debio1347 (CH5183284)
Debio1347 (CH5183284) capsules or tablets for oral administration
Other Name: CH5183284

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Claudio Zanna, MD +41213210111
Contact: Christian Aeschlimann, MS +41213210111

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02114
Contact: Leena Gandhi, MD, PhD    617-632-5320      
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Keith Flaherty, MD    617-724-4800      
United States, New York
Memorial Sloan-Kettering Hospital Recruiting
New-York, New York, United States, 10065
Contact: Martin Voss, MD    646-422-4631      
United States, Texas
The University of Texas; MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030-4009
Contact: Funda Meric-Bernstam, MD    713-794-1226      
Spain
Vall d'Hebron University Hospital Recruiting
Barcelona, Spain
Contact: Josep Tabernero, MD    +34-93-489-43-01      
Sponsors and Collaborators
Debiopharm International SA
Investigators
Study Chair: José Baselga, MD, PhD Memorial Sloan-Kettering Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Debiopharm International SA
ClinicalTrials.gov Identifier: NCT01948297     History of Changes
Other Study ID Numbers: Debio 1347-101, 2013-000316-19
Study First Received: August 26, 2013
Last Updated: June 10, 2015
Health Authority: United States: Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios

ClinicalTrials.gov processed this record on August 03, 2015