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

August 26, 2013
June 10, 2015
August 2013
July 2017   (final data collection date for primary outcome measure)
  • 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
Incidence rate of dose limiting toxicities (DLTs) of Debio 1347 [ Time Frame: Approximately 18 months ] [ Designated as safety issue: Yes ]
The dose escalation part of the study will be guided by a well-established statistical method/model to estimate the maximum tolerated dose(s) and/or the recommended dose for expansion (RDE). Safety(incidence and nature of DLTs), pharmacokinetic and pharmacodynamic data will guide dose escalation decisioins.
Complete list of historical versions of study NCT01948297 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Safety and tolerability of Debio 1347 combination at the recommended dose (RDE) for expansion [ Time Frame: Every 28 days from baseline visit to 28 days after study drug discontinuation ] [ Designated as safety issue: Yes ]
    This will be assessed by looking at the number of Adverse Events (AEs), serious AEs (SAEs) changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions and reductions
  • Markers of FGFR inhibition (FGF-23 and FGF-2) in plasma and tumor [ Time Frame: Baseline and day 8 ] [ Designated as safety issue: No ]
  • Time vs. concentration profile of Debio 1347 [ Time Frame: Every 28 days for up to the end of the study ] [ Designated as safety issue: Yes ]
    Plasma concentration versus time profiles. Plasma PK parameters will be used to characterize the PK profiles of Debio 1347
Not Provided
Overall response rate [ Time Frame: Every 8 weeks from the date of baseline visit ] [ Designated as safety issue: No ]
Assessment of preliminary antitumor activity of Debio 1347; Overall response rate = complete response + partial response
 
Debio 1347-101 Phase I Trial in Advanced Solid Tumours With Fibroblast Growth Factor Receptor (FGFR) Alterations
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

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Solid Tumours
Drug: Debio1347 (CH5183284)
Debio1347 (CH5183284) capsules or tablets for oral administration
Other Name: CH5183284
  • Experimental: Part A
    Adaptive doses of Debio1347 (CH5183284) - (10 mg to 210 mg/day) until the recommended dose (RD) is determined.
    Intervention: Drug: Debio1347 (CH5183284)
  • Experimental: Part B
    Participants with various tumours receive Debio1347 (CH5183284) orally at the recommended dose established during Part A.
    Intervention: Drug: Debio1347 (CH5183284)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
112
December 2017
July 2017   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Claudio Zanna, MD +41213210111
Contact: Christian Aeschlimann, MS +41213210111
United States,   Spain
 
NCT01948297
Debio 1347-101, 2013-000316-19
No
Debiopharm International SA
Debiopharm International SA
Not Provided
Study Chair: José Baselga, MD, PhD Memorial Sloan-Kettering Hospital
Debiopharm International SA
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP