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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by ArQule
Sponsor:
Information provided by (Responsible Party):
ArQule
ClinicalTrials.gov Identifier:
NCT01752920
First received: December 14, 2012
Last updated: June 21, 2016
Last verified: June 2016
  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 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.

Condition Intervention Phase
Solid Tumor
Drug: ARQ 087
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by ArQule:

Primary Outcome Measures:
  • Adverse events graded by CTCAE v4.03 as a measure of the safety and tolerability profile of ARQ 087 [ Time Frame: Assessed at each scheduled visit up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Characterize the pharmacokinetic (PK) profile of ARQ 087 [ 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 ] [ Designated as safety issue: No ]
    Single dose PK parameters include the peak plasma concentration (Cmax), area under the plasma concentration vs. time curve (AUC), and half-life of ARQ 087

  • Assess pharmacodynamic (PD) activity of ARQ 087 [ 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
  • 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) [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ] [ Designated as safety issue: Yes ]
  • Evaluate tumor response assessed by RECIST v1.1 after treatment with ARQ 087 [ Time Frame: Baseline and every 8 weeks or as otherwise clinically indicated ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: December 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARQ 087

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.

Drug: ARQ 087
Subjects in this study will receive ARQ 087 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01752920

Contacts
Contact: ArQule, Inc. 781-994-0300 ClinicalTrials@arqule.com

Locations
United States, Arizona
Completed
Scottsdale, Arizona, United States, 85258
United States, Georgia
Recruiting
Atlanta, Georgia, United States, 30322
United States, Michigan
Completed
Detroit, Michigan, United States, 48201
United States, Nevada
Recruiting
Las Vegas, Nevada, United States, 89169
United States, New York
Recruiting
Bronx, New York, United States, 10467
United States, Pennsylvania
Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Recruiting
San Antonio, Texas, United States, 78229
United States, Washington
Recruiting
Seattle, Washington, United States, 98109
Italy
Not yet recruiting
Benevento, Italy, 82100
Recruiting
Milan, Italy, 20133
Recruiting
Padova, Italy, 35128
Recruiting
Pisa, Italy, 56126
Recruiting
Rozzano, Milan, Italy, 20089
Sponsors and Collaborators
ArQule
  More Information

Responsible Party: ArQule
ClinicalTrials.gov Identifier: NCT01752920     History of Changes
Other Study ID Numbers: ARQ 087-101 
Study First Received: December 14, 2012
Last Updated: June 21, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by ArQule:
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

Additional relevant MeSH terms:
Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on December 02, 2016