Dose Escalation Study of ARQ 197 in Combination With Gemcitabine in Adult Patients With Advanced Solid Tumors

• Status: Completed
• Trial end date: 2011-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, dose-escalation/de-escalation study of ARQ 197 administered orally in combination with gemcitabine. The study is designed to determine the safety, tolerability and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of ARQ 197 when administered in combination with gemcitabine to patients with advanced solid tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

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

Criteria

Inclusion Criteria:

• Written informed consent granted prior to initiation of any study-specific screening procedures, given with the understanding that the patient has the right to withdraw from the study at any time, without prejudice

• 18 year of age or older

• Histologically or cytologically confirmed locally advanced, inoperable or metastatic primary solid tumors

• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1

• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN with metastatic liver disease

• Hemoglobin ≥ 10 g/dl (or ≥ 9 g/dl for expanded cohort)

• Total bilirubin ≤ 1.5 x ULN

• Serum creatinine ≤ 1.5 x ULN

• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

• Platelets ≥ 100 x 10^9/L

• Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug

• Male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received

Exclusion Criteria:

• Other cancer within the last three years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri or basal or squamous cell carcinoma of the skin

• Previous anti-cancer chemotherapy, radiotherapy, major surgery, immunotherapy or investigational agents within 4 weeks prior to the first day of study defined treatment

• History of cardiac disease: congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); previously diagnosed bradycardia or other cardiac arrhythmia defined as ≥ Grade 2 according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (version 3.0), or uncontrolled hypertension; myocardial infarction occurred within 6 months prior to study entry (myocardial infarction occurred > 6 months prior to study entry is permitted)

• Active clinically serious infections defined as ≥ Grade 2 according to NCI CTCAE, version 3.0

• Substance abuse, medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the patient's participation in the study or evaluation of the study results

• Any condition that is unstable or which could jeopardize the safety of the patient and his/her protocol compliance

• Known human immunodeficiency virus (HIV) infection

• Pregnancy or breast-feeding

• Inability to swallow oral medications

• Significant gastrointestinal disorder, in the opinion of the Investigator, could interfere with the absorption of ARQ 197 and/or gemcitabine (e.g. significant, uncontrolled inflammatory bowel disease or extensive small bowel resection)

• Central nervous system metastases