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

NCT01225536 | Completed Phase 1

• 1 other identifier: ARQ 736-101
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 4

Brief Summary

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.

Conditions

Solid Tumor

Keywords

BRAF mutations

Outcome Measures

Primary Outcomes (1)

• Assess safety and tolerability of study drug in subjects with advanced solid tumors who have BRAF and/or NRAS mutations

  Up to treatment discontinuation + 30 days with an estimated treatment duration of 24 weeks

Secondary Outcomes (4)

• Assess pharmacokinetic profile

  During first cycle of treatment (28 days)

• Assess pharmacodynamic activity

  During first cycle of treatment (28 days) plus Day 1 of each consecutive cycle with an estimated treatment duration of 24 weeks

• Determine preliminary evidence of activity

  Up to treatment discontinuation with an estimated treatment duration of 24 weeks

• Determine recommended Phase 2 dose

  Up to treatment discontinuation with an estimated treatment duration of 24 weeks

Study Arms (1)

ARQ 736

EXPERIMENTAL

Drug: ARQ 736

Interventions

ARQ 736 DRUG

Subjects in this study will receive ARQ 736 orally at dose levels specified for their respective dose cohorts. Dosing will begin at 900 mg/day (first cohort) and escalate until the recommended Phase 2 dose or maximum tolerated dose 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.

ARQ 736

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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

Sponsors & Collaborators

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

Study Sites (4)

Unknown Facility

Los Angeles, California, 90025, United States

Location

Unknown Facility

New Haven, Connecticut, 06520, United States

Location

Unknown Facility

New Brunswick, New Jersey, 08903, United States

Location

Unknown Facility

Rozzano, 20089, Italy

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2010
• First Posted: October 21, 2010
• Study Start: October 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: March 1, 2013
• Last Updated: May 3, 2013

Record last verified: 2013-05

Locations

US (3); IT (1)