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 August 2014 by Debiopharm International SA
Sponsor:
Information provided by (Responsible Party):
Debiopharm International SA
ClinicalTrials.gov Identifier:
NCT01948297
First received: August 26, 2013
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

This study is primarily designed to assess the safety and the tolerability of Debio 1347(CH5183284) at increasing doses in patients with advanced solid malignancies, whose tumours have an alteration of the Fibroblast Growth Factor Receptor (FGFR) 1, 2 or 3 genes.


Condition Intervention Phase
Solid Tumours
Drug: Debio 1347 (CH5183284)
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group 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 Fibroblast Growth Factor Receptor (FGFR) 1, 2 or 3 Genes

Resource links provided by NLM:


Further study details as provided by Debiopharm International SA:

Primary Outcome Measures:
  • 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 decisions.


Secondary Outcome Measures:
  • 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 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


Other Outcome Measures:
  • 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


Estimated Enrollment: 106
Study Start Date: August 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Debio 1347 (CH5183284)
Eligible patients will receive Debio 1347(CH5183284)
Drug: Debio 1347 (CH5183284)
Debio 1347 (CH5183284) will be administered orally once daily on a continuous basis 28 day cycles until progression of disease or unacceptable toxicity.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Signed written informed consent approved before undertaking any study-specific procedures.
  2. Patients with advanced solid malignancies, whose tumours have an alteration of the FGFR 1, 2 or 3 genes, confirmed by local site genetic tests on a biopsy.
  3. Age ≥ 18 years.
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2.
  5. Histologically or cytologically confirmed advanced solid tumour that has recurred or progressed following standard therapy, has not responded to standard therapy or for which no standard therapy exists.
  6. Patients have measurable or non-measurable disease.
  7. Adequate organ function in bone marrow, cardiovascular, hepatic and renal systems.

Exclusion Criteria:

  1. History of hypersensitivity to any of the excipients in the Debio 1347 (CH5183284) formulation.
  2. History of another malignancy, unless patient has been disease-free for 5 years.
  3. Patients with brain tumours and/or brain metastases unless brain metastases are asymptomatic and they are not currently receiving corticosteroids and/or anticonvulsants.
  4. History and/or current evidence of endocrine alteration of calcium-phosphate homeostasis.
  5. History and or current evidence of ectopic mineralisation/calcification including but not limited to the soft tissue, kidneys, intestine, myocardium and lung with the exception of calcified lymph nodes and asymptomatic coronary calcification.
  6. Concomitant use of a systemic steroid or any other drug that affect calcium and phosphorus metabolism.
  7. Corneal disease, such as bullous or band keratopathy, corneal desquamation, keratitis, corneal ulcer, or keratoconjunctivitis.

Other protocol-defined inclusion/exclusion criteria may apply.

  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 Active, not recruiting
Boston, Massachusetts, United States, 02114
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      
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
Study First Received: August 26, 2013
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Additional relevant MeSH terms:
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 20, 2014