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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01752920
Recruitment Status : Completed
First Posted : December 19, 2012
Last Update Posted : October 31, 2019
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Information provided by (Responsible Party):
Basilea Pharmaceutica

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.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: Derazantinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 119 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 10, 2012
Actual Primary Completion Date : September 25, 2018
Actual Study Completion Date : September 25, 2018

Arm Intervention/treatment
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.

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.

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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 ]
  4. 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 ]
  5. Evaluate tumor response assessed by RECIST v1.1 after treatment with derazantinib [ Time Frame: Baseline and every 8 weeks or as otherwise clinically indicated ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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 identifier (NCT number): NCT01752920

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United States, Arizona
Scottsdale Healthcare Research Institute
Scottsdale, Arizona, United States, 85258
United States, Georgia
Emory University, Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Michigan
Karmanos Cancer Institute, Detroit
Detroit, Michigan, United States, 48201
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169
United States, New York
Montefiore-Einstein Center for Cancer Care
Bronx, New York, United States, 10467
United States, Pennsylvania
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
START - South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, United States, 78229
United States, Washington
University of Washington
Seattle, Washington, United States, 98109
Istituto Clinico Humanitas
Milan, Italy, 20089
Istituto Nazionale Tumori (National Cancer Institute)
Milan, Italy, 20133
Instituto Oncologico Veneto, IRCCS
Padova, Italy, 35128
Azienda Ospedaliero-Universitaria Pisana - U.O. Oncologia Medica 2 Univ.
Pisa, Italy, 56126
Sponsors and Collaborators
Basilea Pharmaceutica
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
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Study Director: Stephan Braun, MD Basilea Pharmaceutica
Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Basilea Pharmaceutica Identifier: NCT01752920    
Other Study ID Numbers: ARQ 087-101
First Posted: December 19, 2012    Key Record Dates
Last Update Posted: October 31, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Basilea Pharmaceutica:
ARQ 087
Targeted therapy
Molecular therapy
Tyrosine kinase inhibitor
Receptor tyrosine kinase
Phase 1
Phase I
Solid tumor
Liver Cancer
Hepatobiliary carcinoma
Biliary tract cancer
Intrahepatic cholangiocarcinoma
FGFR inhibitor
Targeted FGFR kinase inhibitor
Pan-FGFR inhibitor
Selective FGFR inhibitor
FGFR pathway
FGFR signaling
Fibroblast growth factor
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type