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

NCT01752920

Description:

This is an open-label, Phase 1/2, dose escalation and signal finding study of ARQ 087 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 ARQ 087 and to define a RP2D of ARQ 087.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Phase 1/2 Study of ARQ 087 in Adult Subjects With Advanced Solid Tumors With <span class="go-doc-concept go-doc-biomarker">FGFR</span> <span class="go-doc-concept go-doc-keyword">Genetic</span> Alterations

Title

  • Brief Title: Phase 1/2 Study of ARQ 087 in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations
  • Official Title: A Phase 1/2 Study of ARQ 087 in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations, Including Intrahepatic Cholangiocarcinoma With FGFR2 Gene Fusion
  • Clinical Trial IDs

    NCT ID: NCT01752920

    ORG ID: ARQ 087-101

    Trial Conditions

    Solid Tumor

    Trial Interventions

    Drug Synonyms Arms
    ARQ 087 ARQ 087

    Trial Purpose

    This is an open-label, Phase 1/2, dose escalation and signal finding study of ARQ 087
    administered to subjects with advanced solid tumors. The study is designed to explore the
    safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ARQ
    087 and to define a RP2D of ARQ 087.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    ARQ 087 Experimental Subjects will receive ARQ 087 orally at dose levels specified for their respective dose cohorts on a 28-day schedule. Subjects will receive treatment with ARQ 087 until progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria is documented. ARQ 087

    Eligibility Criteria

    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 ARQ 087.

    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 ARQ 087

    2. Major surgery or radiation therapy within four weeks of the first dose of ARQ 087

    3. Previous treatment with FGFR inhibitors

    4. History of allergic reactions attributed to compounds of similar chemical or
    biological composition as ARQ 087

    5. Unable or unwilling to swallow the complete daily dose of ARQ 087

    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 ARQ 087 (MI occurring >6 months of the first dose of ARQ 087 will be
    permitted)

    8. Significant GI disorder(s) that could interfere with the absorption, metabolism, or
    excretion of ARQ 087 (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 ARQ 087, 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Adverse events graded by CTCAE v4.03 as a measure of the safety and tolerability profile of ARQ 087

    Secondary Outcome Measures

    Characterize the pharmacokinetic (PK) profile of ARQ 087

    Assess pharmacodynamic (PD) activity of ARQ 087

    Evaluate dose limiting toxicity (DLT) graded per CTCAE v4.03 to determine the recommended Phase 2 dosing (RP2D) regimen

    Evaluate further the RP2D of ARQ 087 in subjects with FGFR genetic alterations, including subjects with iCCA with FGFR2 gene fusion (Part 2; Expanded Cohort, signal finding)

    Evaluate tumor response assessed by RECIST v1.1 after treatment with ARQ 087

    Trial Keywords

    FGFR

    ARQ 087

    Targeted therapy

    Molecular therapy

    Tyrosine kinase inhibitor

    TKI

    Receptor tyrosine kinase

    RTK

    Biomarker

    Phase 1

    Phase I

    Solid tumor

    Liver Cancer

    Hepatobiliary carcinoma

    Biliary tract cancer

    Cholangiocarcinoma

    Intrahepatic cholangiocarcinoma

    FGFR inhibitor

    Targeted FGFR kinase inhibitor

    Pan-FGFR inhibitor

    Selective FGFR inhibitor

    FGFR pathway

    FGFR signaling

    Fibroblast growth factor

    FGFR1

    FGFR2

    FGFR3

    FGFR4

    FGF

    FGF19

    FGF21

    FGF23

    FGFR mutation

    FGFR gene fusion

    FGFR gene translocation

    FGFR genetic aberration

    FGFR2 fusion

    FGFR2 translocation

    Phase 1 Clinical Trial

    Phase I Clinical Trial

    Clinical oncology

    Tumor

    Tumour