Clinical trial NCT00302172: ARQ 197 in Subjects With Metastatic Solid Tumors
Official title: A Phase 1 Dose Escalation Study of ARQ 197 in Adult Patients With Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Tumor
Keywords: Cancer
solid tumor
metastatic
primary tumor
Lead sponsor: ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
Sponsor class: INDUSTRY
First posted: 2006-03-14
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To determine the safety, tolerability and recommended Phase 2 dose (RP2D) of 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).

Eligibility criteria: 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

Primary outcomes:
measure: safety, tolerability
timeFrame: All patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
Secondary outcomes:
measure: To determine the pharmacokinetic profile of ARQ 197.
timeFrame: All patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
measure: To determine the pharmacodynamics (i.e., identify biomarkers) of ARQ 197.
timeFrame: All patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
measure: To assess the preliminary anti-tumor activity of ARQ 197.
timeFrame: All patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Premiere Oncology
state: California
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
Study officials:
References: