Dose Escalation Study of ARQ 736 in Adult Subjects With Advanced Solid Tumors Harboring BRAF and/or NRAS Mutations

Completed · Phase 1

Conditions studied: Solid Tumor

In brief

This is an open-label, Phase 1, dose escalation study of oral ARQ 736 administered to subjects with advanced solid tumors harboring the mutation. The study is designed to explore the safety, tolerability, pharmacokinetics and pharmacodynamics of ARQ 736 and to define a recommended Phase 2 dose of ARQ 736.

Key facts

Study ID

NCT01225536

Run by

ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

People needed

24

Starts

2010-10-01

Expected to finish

2013-03-01

Last updated by the study team

2013-05-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Signed written informed consent granted prior to initiation of any study-specific procedures
• Male or female subjects of ≥ 18 years of age
• All subjects must be positive for a BRAF and/or NRAS mutation
• Histologically or cytologically confirmed locally advanced, inoperable or metastatic solid tumors
• Failure to respond to at least one prior systemic therapy (including previous treatment with BRAF inhibitors) or to whom standard or curative therapy does not exist
• Life expectancy of greater than three months
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
• Hemoglobin (Hgb) ≥10 g/dl
• Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L
• Platelet count ≥100 x 10\^9/L
• Total bilirubin ≤1.5 × upper limit of normal (ULN)
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × ULN (≤5 x ULN for subjects with liver metastases)
• Serum creatinine ≤1.5 × ULN or creatinine clearance >60 mL/min/1.73 m\^2 for subjects with creatinine levels above institutional normal
• Left Ventricular Ejection Fraction (LVEF) ≥ the institutional lower limit normal (ILLN)
• Male or female subjects of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception or avoidance of intercourse during the study and for 30 days after the last dose of ARQ 736
• Females of childbearing potential must have a negative serum pregnancy test within seven days prior to the first dose of ARQ 736
• Must agree to have tumor and/or skin (nevi) biopsy at baseline and on Day 15 or Day 22 of Cycle 1. Tumor biopsy will be done if the subject has a lesion for which in the Investigator's opinion a non- or minimally invasive tumor biopsy may be performed. If tumor biopsy is not available, skin (nevi) biopsy should be performed.

You may not qualify if…

• Anti-cancer chemotherapy, immunotherapy, or investigational agents within four weeks of the first dose of ARQ 736
• Major surgery or radiotherapy within two weeks of the first dose of ARQ 736
• Brain metastases that are progressing or have been documented to be stable for less than six weeks, or for which systemic corticosteroids are required
• History of allergic reactions attributed to compounds of similar chemical or biologic composition as ARQ 736
• Unable or unwilling to swallow the complete daily dose of ARQ 736
• Significant gastrointestinal disorder(s), in the opinion of the Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
• History of myocardial infarction (MI) within 6 months of the administration of the first dose of ARQ 736 (MI occurring > 6 months of the first dose of ARQ 736 will be permitted)
• History of congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification within 6 months of the administration of the first dose of ARQ 736
• Previous malignancy within 2 years of the first dose of ARQ 736, except carcinoma in-situ of the cervix
• Concurrent uncontrolled illness, including but not limited to:
• Ongoing or active infection, including human immunodeficiency virus (HIV) infection or bleeding
• Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements
• Blood transfusion within five days prior to blood draw being used to confirm eligibility

Where it is running

• Study site — Los Angeles, California, United States
• Study site — New Haven, Connecticut, United States
• Study site — New Brunswick, New Jersey, United States
• Study site — Rozzano, Italy

Full record on ClinicalTrials.gov

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