ARQ 197 in Subjects With Metastatic Solid Tumors

A Phase 1 Dose Escalation Study of ARQ 197 in Adult Patients With Metastatic Solid Tumors

To determine the safety, tolerability and recommended Phase 2 dose (RP2D) of ARQ 197.

Study Overview

• Status: Completed
• Conditions: Cancer; Tumor
• Intervention / Treatment: Drug: ARQ 197

Detailed Description

To determine the safety, tolerability and recommended Phase 2 dose (RP2D) of ARQ 197 given orally. This is an open label, dose escalation study of ARQ 197 administered orally at a starting dose of 10 mg bid (20 mg/day).

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90404
      • Premiere Oncology
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic
  • Texas
    • Dallas, Texas, United States, 75246
      • Mary Crowley Medical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed written informed consent must be obtained and documented according to ICH GCP, the local regulatory requirements, and permission to use private health information in accordance with HIPPA prior to study-specific screening procedures
• A histologically or cytologically confirmed RCC or other c-Met expression tumors that is metastatic
• Patient must have available archival tumor tissue or accessible tumor that is safely amenable to tumor biopsy
• ≥ 18 years of age
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
• Karnofsky performance status ≥ 70%
• Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last ARQ 197 dose
• Females of childbearing potential must have a negative serum pregnancy test
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN) or ≤ 5.0 × ULN with metastatic liver disease.
• Hemoglobin (Hgb) ≥ 10 g/dl
• Total bilirubin ≤ 1.5 × ULN
• Creatinine ≤ 1.5 x ULN
• Absolute neutrophil count ≥ 1.5 x 10^9/L
• Platelets ≥ 100 x 10^9/L

Exclusion Criteria:

• Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within four weeks of first dose
• Surgery within 4 weeks prior to first dose
• Known brain metastases
• Pregnant or breastfeeding
• Significant gastrointestinal disorder(s), in the opinion of the Principal Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
• Unable or unwilling to swallow ARQ 197 capsules twice daily
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements
• Bradycardia at baseline or known history of arrhythmia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ARQ 197

Drug: ARQ 197; Patients in this trial will receive ARQ 197 orally at dose levels specified for their respective dose cohorts. Dosing will begin at 20 mg/day (first cohort) and escalate until the RP2D or MTD is determined. Patients enrolled under a previous amendment will continue to receive ARQ 197 twice daily for 14 days followed by 7 days without therapy. Any patient enrolled under Amendment 3 will take ARQ 197 twice daily for 21 days where cycles will be repeated every three-weeks (21 days). Patients enrolled under Amendment 4 will receive dose of 360 mg bid (720 mg daily) continuously for 21 days, and cycle will be repeated every three weeks. All patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment is permitted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
safety, tolerability	All patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the pharmacokinetic profile of ARQ 197.	All patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
To determine the pharmacodynamics (i.e., identify biomarkers) of ARQ 197.	All patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
To assess the preliminary anti-tumor activity of ARQ 197.	All patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met

Collaborators and Investigators

• Sponsor: ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Study record dates

Study Major Dates

• Study Start: January 1, 2006

Study Registration Dates

• First Submitted: March 10, 2006
• First Submitted That Met QC Criteria: March 10, 2006
• First Posted (Estimate): March 14, 2006

Study Record Updates

• Last Update Posted (Estimate): August 26, 2009
• Last Update Submitted That Met QC Criteria: August 25, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Keywords: Cancer; solid tumor; metastatic; primary tumor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ARQ 197-101