Clinical trial NCT01473095: Phase 1 Dose Escalation Study of ARQ 092 in Adult Subjects With Advanced Solid Tumors and Recurrent Malignant Lymphoma
Official title: A Phase 1 Dose Escalation Study of ARQ 092 in Adult Subjects With Advanced Solid Tumors and Recurrent Malignant Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Malignant Lymphoma
Tumor
Keywords: AKT
ARQ 092
Targeted therapy
Molecular therapy
Biomarker
Phase 1
Phase I
Endometrial cancer
Lymphoma
AKT pathway
AKT signaling
AKT inhibitor
AKT pan inhibitor
AKT1
AKT2
AKT3
AKT1 mutation
AKT1-E17K
AKT1-E17K mutation
AKT 2 inhibitor
AKT 3 inhibitor
AKT 3 amplification
PI3K AKT mTOR signalling pathway
mTOR inhibitor
PI3K inhibitor
Clinical oncology
Tumor
Tumour
PIK3CA H1047R mutation
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: 2011-11-17
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Men or women ≥18 years old
2. 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.
3. Evaluable or measurable disease
4. Life expectancy greater than three months
5. ECOG performance status ≤2
6. Hemoglobin (Hgb) ≥9.5 g/dl
7. Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L
8. Platelet count ≥75 x 10\^9/L
9. Total bilirubin ≤1.5 × upper limit of normal (ULN)
10. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 × ULN
11. 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
12. 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:

1. 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.
2. Grade 2 or worse hypercholesterolemia or hypertriglyceridemia or \>8% glycated Hb (HbA1C)
3. Malabsorption syndrome
4. Known brain metastases not radiographically stable for ≥3 months or leptomeningeal disease
5. 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
6. 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)
7. Major surgery within four weeks of the first dose of ARQ 092
8. Previous treatment with AKT inhibitors
9. Concurrent severe uncontrolled illness not related to cancer
10. Ongoing or active known infection, including human immunodeficiency virus (HIV) infection or bleeding
11. Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements.
12. Blood transfusion within 5 days prior to blood draw being used to confirm eligibility
13. Pregnant or breastfeeding
14. 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.

Primary outcomes:
measure: 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
timeFrame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 16 weeks
Secondary outcomes:
measure: Assess the pharmacokinetic profile (Cmax, AUC, and half-life) of ARQ 092
timeFrame: During the first 29 days of treatment for each dose level
measure: Assess pharmacodynamic activity
timeFrame: During the first 29 days of treatment
measure: Determine preliminary evidence of activity as defined by RECIST v 1.1
timeFrame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 16 weeks
measure: Determine recommended Phase 2 dose
timeFrame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 16 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Scottsdale
country: United States
state: Arizona
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Atlanta
country: United States
state: Georgia
city: Lafayette
country: United States
state: Indiana
city: San Antonio
country: United States
state: Texas
Study officials:
References: