NCT00874042CompletedPhase 1
A Phase 1 Dose Escalation Study of ARQ 197 Administered in Combination With Gemcitabine in Adult Patients With Advanced Solid Tumors
ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)0 sites74 target enrollmentStarted: March 2009Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 74
- Primary Endpoint
- 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.
Study Overview
Brief 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.
Detailed Description
Enrollment of an initial cohort of 3 or 6 patients will follow the traditional "3 + 3" dose escalation scheme. These patients will be treated with ARQ 197 and gemcitabine. ARQ 197 will be administered by mouth BID continuously. Gemcitabine will be administered by intravenous infusion over 30 minutes once weekly for 3 consecutive weeks followed by a week of rest. The dosing schedules of ARQ 197 and gemcitabine will be as described below.
ARQ 197 will be administered per the following cohorts, starting from week 1 of treatment.
Cohort------ARQ 197 (mg BID)
0-----------120, continuously
1-----------240, continuously
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
ARQ 197 in combination with gemcitabine
Experimental
Intervention: Treatment with ARQ 197 in combination with gemcitabine (Drug)
Outcomes
Primary Outcomes
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.
Time Frame: Patients will remain on study until unacceptable toxicity, disease progression (clinical or radiological) or another discontinuation criterion is met.
Secondary Outcomes
- To determine the pharmacokinetic profiles of ARQ 197, gemcitabine and dFdU inactive metabolite of gemcitabine when administered in combination.
- To assess the preliminary anti-tumor activity of ARQ 197 when administered in combination with gemcitabine.(Patients will remain on study until unacceptable toxicity, disease progression (clinical or radiological) or another discontinuation criterion is met.)
- To evaluate dynamic changes of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and soluble c-Met in patients' peripheral blood that are associated with treatment of ARQ 197 plus gemcitabine.(Patients will remain on study until unacceptable toxicity, disease progression (clinical or radiological) or another discontinuation criterion is met.)
Investigators
Similar Trials
Completed
Phase 1
A Phase 1 Study of ARQ 197 in Adult Patients With Advanced Solid TumorsCancer, Advanced Solid TumorsNCT00612209ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)51
Completed
Phase 1
A Phase 1 Study of ARQ 197 in Patients With Solid TumorsCancerNCT00609921Kyowa Kirin Co., Ltd.42
Completed
Phase 1
Dose Escalation Study of ARQ 197 in Combination With Sorafenib in Adult Patients With Advanced Solid TumorsAdvanced Solid TumorsNCT00827177ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)87
Completed
Phase 1
A Phase 1 Study of ARQ 197 in Adult Patients With Advanced Solid TumorsCancerNCT00612703ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)32
Completed
Phase 1
Phase 1 Dose Escalation Study of ARQ 092 in Adult Subjects With Advanced Solid Tumors and Recurrent Malignant LymphomaSolid TumorMalignant LymphomaTumorNCT01473095ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)120