Phase 1 Dose Escalation Study of ARQ 092 in Adult Subjects With Advanced Solid Tumors and Recurrent Malignant Lymphoma

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT01473095

Collaborator

(none)

120

Enrollment

Locations

69.2

Duration (Months)

17.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, Phase 1, dose escalation study of oral ARQ 092 administered to subjects with advanced solid tumors and recurrent malignant lymphoma. The study is designed to explore the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARQ 092 and to define a recommended Phase 2 dose of ARQ 092.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Malignant Lymphoma Tumor	Drug: ARQ 092	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Dose Escalation Study of ARQ 092 in Adult Subjects With Advanced Solid Tumors and Recurrent Malignant Lymphoma

Study Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Jul 6, 2017

Actual Study Completion Date :

Aug 7, 2017

Outcome Measures

Primary Outcome Measures

Assess the safety and tolerability of ARQ 092 in subjects with advanced solid tumors and recurrent malignant lymphoma by monitoring frequency and severity of adverse events [Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 16 weeks]

Secondary Outcome Measures

Assess the pharmacokinetic profile (Cmax, AUC, and half-life) of ARQ 092 [During the first 29 days of treatment for each dose level]
Assess pharmacodynamic activity [During the first 29 days of treatment]
Determine preliminary evidence of activity as defined by RECIST v 1.1 [Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 16 weeks]
Determine recommended Phase 2 dose [Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 16 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men or women ≥18 years old
Histologically or cytologically documented, incurable, locally advanced or metastatic solid tumors or recurrent malignant lymphoma in subjects who failed standard therapy or for whom standard or curative therapy does not exist or is not tolerable.
Evaluable or measurable disease
Life expectancy greater than three months
ECOG performance status ≤2
Hemoglobin (Hgb) ≥9.5 g/dl
Absolute neutrophil count (ANC) ≥1.5 x 10^9/L
Platelet count ≥75 x 10^9/L
Total bilirubin ≤1.5 × upper limit of normal (ULN)
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 × ULN
Serum creatinine ≤1.5 x ULN or creatinine clearance > 60 mL/min/1.73 m^2 for subjects with creatinine levels >1.5 x ULN
Agree to use double-barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug

Exclusion Criteria:

History of Type 1 or 2 diabetes mellitus requiring regular medication (other than metformin or other oral hypoglycemic agents) or fasting glucose ≥160 mg/dL at the prestudy visit. If a diabetic cohort is enrolled, only subjects with a medical history of controlled Type 1 or 2 diabetes mellitus will be enrolled in the cohort.
Grade 2 or worse hypercholesterolemia or hypertriglyceridemia or >8% glycated Hb (HbA1C)
Malabsorption syndrome
Known brain metastases not radiographically stable for ≥3 months or leptomeningeal disease
History of myocardial infarction (MI) or NYHA Class II-IV congestive heart failure within 6 months of the administration of the first dose of ARQ 092 (MI occurring >6 months of the first dose of ARQ 092 will be permitted); Grade 2 or worse conduction defect (eg right or left bundle branch block); left ventricular ejection fraction (LVEF) < 50% assessed by echocardiogram/MUGA scan
Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within four weeks of the first dose of ARQ 092 (within 2 weeks for orally administered drugs)
Major surgery within four weeks of the first dose of ARQ 092
Previous treatment with AKT inhibitors
Concurrent severe uncontrolled illness not related to cancer
Ongoing or active known infection, including human immunodeficiency virus (HIV) infection or bleeding
Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements.
Blood transfusion within 5 days prior to blood draw being used to confirm eligibility
Pregnant or breastfeeding
Previous other malignancy within 2 years prior to the first dose of ARQ 092, with the exception of carcinoma in-situ of the cervix, basal cell carcinoma and superficial bladder tumors curatively treated.

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Birmingham	Alabama	United States	35294
2	Scottsdale	Arizona	United States	85258
3	Miami	Florida	United States	33136
4	Atlanta	Georgia	United States	30322
5	Atlanta	Georgia	United States	30341
6	Lafayette	Indiana	United States	47905
7	San Antonio	Texas	United States	78229