Know Cancer

forgot password

A Phase 1 Dose Escalation Study of ARQ 736 in Adult Subjects With Advanced Solid Tumors Harboring BRAF and/or NRAS Mutations

Phase 1
18 Years
Not Enrolling
Solid Tumor

Thank you

Trial Information

A Phase 1 Dose Escalation Study of ARQ 736 in Adult Subjects With Advanced Solid Tumors Harboring BRAF and/or NRAS Mutations

Treatment will be initiated at a dose level of 450 mg twice daily (900 mg/daily). All
cycles/cohorts of therapy will consist of the oral administration of ARQ 736 twice or four
times a day, one hour prior to or two hours after the meal for 28 days continuously. Tumor
assessments (CT scan or MRI) will be performed at Baseline, and every two cycles (every
eight weeks) thereafter or as otherwise clinically indicated. For early assessment of
evidence of biological activity of the tumor PET scan may be performed at Baseline and four
weeks from the administration of the first dose of ARQ 736 (approximately Cycle 2 Day1).

Inclusion Criteria:

- Signed written informed consent granted prior to initiation of any study-specific

- 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

- 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

- 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.

Exclusion Criteria:

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

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

Outcome Time Frame:

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

Safety Issue:



United States: Food and Drug Administration

Study ID:

ARQ 736-101



Start Date:

October 2010

Completion Date:

March 2013

Related Keywords:

  • Solid Tumor
  • BRAF mutations
  • Neoplasms



New Britain, Connecticut  06052
Fountain Valley, California  92708
Hackensack, New Jersey  07601