ARQ 197 in Subjects With Metastatic Solid Tumors

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00302172
• Other study ID #: ARQ 197-101
• Status: Completed
• Phase: Phase 1
• First received: March 10, 2006
• Last updated: August 25, 2009
• Start date: January 2006

Study information

• Verified date: August 2009
• Source: ArQule
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Tumor

Intervention

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.

Locations

Country	Name	City	State
United States	The Cleveland Clinic	Cleveland	Ohio
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Premiere Oncology	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
ArQule

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	safety, tolerability		All patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No