Phase 1 Dose Escalation Study of ARQ 087 in Adult Subjects With Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by ArQule
Sponsor:
Information provided by (Responsible Party):
ArQule
ClinicalTrials.gov Identifier:
NCT01752920
First received: December 14, 2012
Last updated: June 17, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Solid Tumor
Drug: ARQ 087
Phase 1

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 Dose Escalation Study of ARQ 087 in Adult Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by ArQule:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assess the pharmacokinetic profile of ARQ 087 [ Time Frame: During the first 28 days of treatment for each dose level ] [ Designated as safety issue: No ]
    Blood sampling to assess the pharmacokinetic profile of ARQ 087.

  • Assess pharmacodynamic activity [ Time Frame: Up to treatment discontinuation ] [ Designated as safety issue: No ]
    Blood and tumor sampling to provide information on fibroblast growth factor (FGF/FGFR) signalling pathway biomarkers.

  • 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 ] [ Designated as safety issue: No ]
  • Determine recommended Phase 2 dose [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: December 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARQ 087 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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men or women ≥18 years of age
  • Histologically or cytologically confirmed, locally advanced, inoperable, or metastatic solid tumors
  • Failure to respond to standard therapy, or for whom standard therapy does not exist.
  • Evaluable or measurable disease
  • Archival and/or fresh biopsy tissue samples must be available prior to the first dose of the study drug
  • Life expectancy greater than 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Hemoglobin (Hgb) ≥9.0 g/dl
  • Absolute neutrophil count (ANC) ≥1.5 x 109/L
  • Platelet count ≥100 x 109/L
  • Total bilirubin ≤1.5 × upper limit of normal (ULN)
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 × ULN (≤5 for subjects with liver metastases)
  • Serum creatinine ≤1.5 x ULN or creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
  • Men or women of child-producing potential must agree to use double-barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug
  • 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:

  • Anti-cancer chemotherapy, immunotherapy, or investigational agents within four weeks or five times of the drug half life, whichever is longer, of the first dose of ARQ 087
  • Major surgery or radiation therapy within four weeks of the first dose of ARQ 087
  • Previous treatment with FGFR inhibitors
  • History of allergic reactions attributed to compounds of similar chemical or biological composition as ARQ 087
  • Unable or unwilling to swallow the complete daily dose of ARQ 087
  • Clinically unstable central nervous system (CNS) metastasis
  • History of myocardial infarction (MI) or New York Heart Association (NYHA) Class II-IV congestive heart failure within 6 months of the administration of the first dose of ARQ 087 (MI occurring >6 months of the first dose of ARQ 087 will be permitted)
  • 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)
  • History and/or current evidence of clinically relevant ectopic mineralization/calcification
  • Previous other malignancy within 2 years prior to the first dose of ARQ 087, with the exception of curatively treated non-melanoma skin cancer, carcinoma in-situ of the breast or cervix, or superficial bladder tumors
  • Concurrent severe uncontrolled illness not related to cancer, including:

    • Ongoing or active known infection, including human immunodeficiency virus (HIV) infection or bleeding
    • Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements.
    • Uncontrolled diabetes mellitus
  • Blood transfusion within 5 days prior to blood draw being used to confirm eligibility
  • 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, Michigan
Recruiting
Detroit, Michigan, United States, 48201
United States, Texas
Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
ArQule
  More Information

No publications provided

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 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by ArQule:
FGFR

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on August 28, 2014