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Phase 1/2 Study of Derazantinib (ARQ 087) in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations

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ClinicalTrials.gov Identifier: NCT01752920
Recruitment Status : Completed
First Posted : December 19, 2012
Last Update Posted : October 31, 2019
Sponsor:
Collaborator:
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Information provided by (Responsible Party):
Basilea Pharmaceutica

Tracking Information
First Submitted Date  ICMJE December 14, 2012
First Posted Date  ICMJE December 19, 2012
Last Update Posted Date October 31, 2019
Actual Study Start Date  ICMJE December 10, 2012
Actual Primary Completion Date September 25, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 18, 2019)
Adverse events graded by CTCAE v4.03 as a measure of the safety and tolerability profile of derazantinib [ Time Frame: Assessed at each scheduled visit up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 17, 2012)
Assess the safety and tolerability of ARQ 087 in subjects with advanced solid tumors by monitoring frequency and severity of adverse events [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2019)
  • Characterize the pharmacokinetic (PK) profile of derazantinib [ Time Frame: Part 1: t=Days 1, 2, 3, and 4. Cohort 5+: t=Days 1, 2, 8, 15, 22, and 23 of Cycle 1; and t=Days 1 and 15 of subsequent cycles ]
    Single dose PK parameters include the peak plasma concentration (Cmax), area under the plasma concentration vs. time curve (AUC), and half-life of derazantinib
  • Assess pharmacodynamic (PD) activity of derazantinib [ Time Frame: Part 1 t=Days 1, 2, 3, and 4. For Cohort 5+: t=Days 1, 8, 15, 22 of Cycle 1; and t=Days 1 of Cycles 2-5. For Part 2: t=Day 1 of Cycle 1-6 ]
    PD parameters include changes of phosphate, glucose, and FGF 19, 21, and/or 23
  • Evaluate dose limiting toxicity (DLT) graded per CTCAE v4.03 to determine the recommended Phase 2 dosing (RP2D) regimen [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]
  • Evaluate further the RP2D of derazantinib in subjects with FGFR genetic alterations, including subjects with iCCA with FGFR2 gene fusion (Part 2; Expanded Cohort, signal finding) [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]
  • Evaluate tumor response assessed by RECIST v1.1 after treatment with derazantinib [ Time Frame: Baseline and every 8 weeks or as otherwise clinically indicated ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2012)
  • Assess the pharmacokinetic profile (Area under the curve) of ARQ 087 [ Time Frame: During the first 28 days of treatment for each dose level ]
    Blood sampling to assess the pharmokinetic profile (Area under the curve) of ARQ 087.
  • Assess pharmacodynamic activity [ Time Frame: Up to treatment discontinuation ]
    Blood sampling to provide information on tumor FGFR protein expression using immunohistochemistry (IHC).
  • Determine preliminary evidence of activity as defined by standard imaging assessments [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]
  • Determine recommended Phase 2 dose [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1/2 Study of Derazantinib (ARQ 087) in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations
Official Title  ICMJE A Phase 1/2 Study of Derazantinib in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations, Including Intrahepatic Cholangiocarcinoma With FGFR2 Gene Fusion
Brief Summary This is an open-label, Phase 1/2, dose escalation and signal finding study of derazantinib administered to subjects with advanced solid tumors with FGFR genetic alterations, including intrahepatic cholangiocarcinoma (iCCA) with FGFR2 gene fusion. The study is designed to explore the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of derazantinib and to define a RP2D of derazantinib.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE Drug: Derazantinib
Subjects in this study will receive derazantinib orally at dose levels specified for their respective dose cohorts. Dosing will begin at 25 mg every other day (QOD) and will escalate until the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is determined. Cycles will be repeated in four-week (28 day) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted.
Study Arms  ICMJE Experimental: derazantinib

Subjects will receive derazantinib orally at dose levels specified for their respective dose cohorts on a 28-day schedule.

Subjects will receive treatment with derazantinib until progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria is documented.

Intervention: Drug: Derazantinib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 21, 2019)
119
Original Estimated Enrollment  ICMJE
 (submitted: December 17, 2012)
60
Actual Study Completion Date  ICMJE September 25, 2018
Actual Primary Completion Date September 25, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed written informed consent granted
  2. Men or women ≥18 years of age
  3. Histologically or cytologically confirmed, locally advanced, inoperable, or metastatic solid tumors. Subjects eligible for enrollment in the Expanded Cohort must have documented and/or confirmed FGFR genetic alterations, including iCCA with FGFR2 gene fusion.
  4. Failure to respond to standard therapy, or for whom standard therapy does not exist.
  5. Evaluable or measurable disease
  6. Archival and/or fresh biopsy tissue samples must be available prior to the first dose of the study drug
  7. Life expectancy ≥ 12 weeks
  8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  9. Hemoglobin (Hgb) ≥ 9.0 g/dL
  10. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
  11. Platelet count ≥ 100 x 10^9/L
  12. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (≤ 2 x ULN for subjects with cholangiocarcinoma)
  13. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 × ULN (≤ 5 x ULN for subjects with liver metastases)
  14. Serum creatinine ≤ 1.5 x ULN or creatinine clearance > 60 mL/min/1.73 m^2 for subjects with creatinine levels above institutional normal
  15. Albumin ≥ 2.8 g/dL
  16. INR 0.8 to ULN or ≤ 3 for subjects receiving anticoagulant therapy
  17. Men or women of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoid intercourse during the study and for 90 days after the last dose of study drug
  18. Women of childbearing potential must have a negative serum pregnancy test during Screening Period and within 48 hours of the first dose of derazantinib.

Exclusion Criteria:

  1. Anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks or five times of the drug half life, whichever is longer, of the first dose of derazantinib
  2. Major surgery or radiation therapy within four weeks of the first dose of derazantinib
  3. Previous treatment with FGFR inhibitors
  4. History of allergic reactions attributed to compounds of similar chemical or biological composition as derazantinib
  5. Unable or unwilling to swallow the complete daily dose of derazantinib
  6. Clinically unstable central nervous system (CNS) metastasis
  7. History of myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association classification within 6 months of the first dose of derazantinib (MI occurring >6 months of the first dose of derazantinib will be permitted)
  8. Significant GI disorder(s) that could interfere with the absorption, metabolism, or excretion of derazantinib (e.g. Crohn's disease, ulcerative colitis, extensive gastric resection)
  9. History and/or current evidence of clinically relevant ectopic mineralization/calcification
  10. Previous malignancy within 2 years prior to the first dose of derazantinib, except curatively treated non-melanoma skin cancer, carcinoma in-situ of the breast or cervix, or superficial bladder tumors
  11. Known human immunodeficiency virus (HIV) infection
  12. Concurrent uncontrolled illness not related to cancer, including but not limited to:

    • Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements.
    • Uncontrolled diabetes mellitus
  13. Blood transfusion within 5 days of the blood draw being used to confirm eligibility
  14. Pregnant or breastfeeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01752920
Other Study ID Numbers  ICMJE ARQ 087-101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Basilea Pharmaceutica
Study Sponsor  ICMJE Basilea Pharmaceutica
Collaborators  ICMJE ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Investigators  ICMJE
Study Director: Stephan Braun, MD Basilea Pharmaceutica
PRS Account Basilea Pharmaceutica
Verification Date March 2019

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