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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 : March 23, 2018
Sponsor:
Information provided by (Responsible Party):
Debiopharm International SA

Brief 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.


Condition or disease Intervention/treatment Phase
Solid Tumours Drug: Debio1347 (CH5183284) Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : August 2013
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Arm Intervention/treatment
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
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) tablets for oral administration
Other Name: CH5183284



Primary Outcome Measures :
  1. Part A: Percentage of Participants With Dose-Limiting Toxicities (DLTs) From Debio 1347 [ Time Frame: within approximately 18 months ]
  2. Part B: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) [ Time Frame: within 2 years of starting treatment ]
  3. 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 ]
  4. 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

  5. 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


Secondary Outcome Measures :
  1. Part A: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) [ Time Frame: within 2 years of starting treatment ]
  2. 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 ]
  3. Part A: Severity of Treatment-Emergent AEs [ Time Frame: within 2 years of starting treatment ]
    Categories: NCI-CTCAE version 4 severity criteria

  4. Part A: Severity of Laboratory Abnormalities [ Time Frame: within 2 years of starting treatment ]
    Categories: NCI-CTCAE version 4 severity criteria

  5. 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 ]
  6. 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).

  7. 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.

  8. 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.

  9. Part A and Part B: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) [ Time Frame: within 2 years of starting treatment ]
  10. 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 ]
  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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 ]
  16. 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 ]
  17. 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 ]
  18. 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 ]
  19. 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 ]
  20. 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 ]
  21. 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 ]
  22. 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 ]
  23. 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 ]
  24. 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 ]
  25. 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 ]
  26. Part B: Area Under Concentration-Time Curve (AUC), Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  27. 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 ]
  28. Part B: Maximum Observed Concentration (Cmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  29. Part B: Time of Maximum Concentration (tmax) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  30. Part B: Apparent Terminal Half-Life (t1/2) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  31. Part B: Mean Residence Time (MRT) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  32. Part B: Apparent clearance (CL/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  33. Part B: Apparent Volume of Distribution (Vz/F) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  34. Part B: Peak-to-Trough Fluctuation (PTF) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  35. Part B: Renal Clearance (CLR) Following Repeated-Dose Administration of Debio 1347 in the PK Subset [ Time Frame: Day 28 ]
  36. 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 ]
  37. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01948297


Contacts
Contact: Debiopharm International S.A +41 21 321 01 11 clinicaltrials@debiopharm.com

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02114
Contact: James Cleary, MD    617-632-6261      
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Rebecca Heist, MD    617-726-8033      
United States, New York
Memorial Sloan-Kettering Hospital Recruiting
New York, New York, United States, 10065
Contact: Gopakumar Iyer, MD    646-422-4362      
United States, Texas
The University of Texas; MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030-4009
Contact: Funda Meric-Bernstam, MD    713-794-1226      
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Contact: Yung-Jue Bang, MD    +82 2 2072 2390      
Singapore
National Cancer Center Singapore Recruiting
Singapore, Singapore, 169610
Contact: Matthew Ng Chau Hsien, MD    +65 64368000      
Spain
Vall d'Hebron University Hospital Recruiting
Barcelona, Spain
Contact: Josep Tabernero, MD    +34-93-489-43-01      
Contact: Cinta Hierro, MD    +34-93-489-4301      
Taiwan
Taipei Medical University Hospital Recruiting
Taipei, Taiwan, 11031
Contact: Tsu-Yi Chao, MD    +886 2 2249 0088      
Contact: Her-Shyong Shiah, MD    +886 2 2737 2181      
Sponsors and Collaborators
Debiopharm International SA

Additional Information:
Responsible Party: Debiopharm International SA
ClinicalTrials.gov Identifier: NCT01948297     History of Changes
Other Study ID Numbers: Debio 1347-101
2013-000316-19 ( EudraCT Number )
First Posted: September 23, 2013    Key Record Dates
Last Update Posted: March 23, 2018
Last Verified: March 2018