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

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ClinicalTrials.gov Identifier: NCT01948297
Recruitment Status : Recruiting
First Posted : September 23, 2013
Last Update Posted : May 30, 2018
Sponsor:
Information provided by (Responsible Party):
Debiopharm International SA

August 26, 2013
September 23, 2013
May 30, 2018
August 2013
December 2018   (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 ]
  • Part B: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) [ Time Frame: within 2 years of starting treatment ]
  • 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 ]
  • Part B: Severity of Treatment-Emergent AEs [ Time Frame: within 2 years of starting treatment ]
    Categories: NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4 severity criteria
  • Part B: Severity of Laboratory Abnormalities [ Time Frame: within 2 years of starting treatment ]
    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 ]
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 Serious Adverse Events (SAEs) [ Time Frame: within 2 years of starting treatment ]
  • 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 ]
  • Part A: Severity of Treatment-Emergent AEs [ Time Frame: within 2 years of starting treatment ]
    Categories: NCI-CTCAE version 4 severity criteria
  • Part A: Severity of Laboratory Abnormalities [ Time Frame: within 2 years of starting treatment ]
    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 ]
  • Part A and Part B: Number of Participants With Change From Baseline in Blood Pressure (BP) [ Time Frame: within 2 years of starting treatment ]
    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).
  • Part A and Part B: Number of Participants With Change From Baseline in Pulse Rate [ Time Frame: within 2 years of starting treatment ]
    Number of participants with change of more than 20 beats per minute from baseline will be reported.
  • Part A and Part B: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters [ Time Frame: within 2 years of starting treatment ]
    ECG parameters will include PR, RR, QRS, QTcB and QTcF intervals.
  • Part A and Part B: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) [ Time Frame: within 2 years of starting treatment ]
  • 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 ]
  • 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 ]
    Includes: Best overall response, disease control, tumour size
  • 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 ]
    Includes: Best overall response, disease control, tumour size
  • Part A and Part B: Progression-Free Survival Rate After Treatment Initiation [ Time Frame: within 2 years of starting treatment ]
    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 ]
    Opthalmological exams includes visual acuity testing, slit-lamp ophthalmoscopy and indirect ophthalmoscopy.
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Part B: Area Under Concentration-Time Curve (AUC), Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  • 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 ]
  • Part B: Maximum Observed Concentration (Cmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  • Part B: Time of Maximum Concentration (tmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  • Part B: Apparent Terminal Half-Life (t1/2) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  • Part B: Mean Residence Time (MRT) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  • Part B: Apparent clearance (CL/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  • Part B: Apparent Volume of Distribution (Vz/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  • Part B: Peak-to-Trough Fluctuation (PTF) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  • Part B: Renal Clearance (CLR) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  • 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 ]
  • 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 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 ]
    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 ]
  • Time vs. concentration profile of Debio 1347 [ Time Frame: Every 28 days for up to the end of the study ]
    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 ]
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
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Solid Tumours
Drug: Debio1347 (CH5183284)
Debio1347 (CH5183284) 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
106
December 2018
December 2018   (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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: Debiopharm International S.A +41 21 321 01 11 clinicaltrials@debiopharm.com
Korea, Republic of,   Singapore,   Spain,   Taiwan,   United States
 
 
NCT01948297
Debio 1347-101
2013-000316-19 ( EudraCT Number )
No
Not Provided
Not Provided
Debiopharm International SA
Debiopharm International SA
Not Provided
Not Provided
Debiopharm International SA
May 2018

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