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

NCT01473095 | Completed Phase 1

• 1 other identifier: ARQ 092-101
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 7

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Interventions

ARQ 092 DRUG

Subjects in this study will receive ARQ 092 orally at dose levels specified for their respective dose cohorts. Dosing will begin at 10 mg every other day (QOD) and will escalate until the MTD or RP2D is determined. Cycles will be repeated in four-week (28 day) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA): lead

Study Sites (7)

Unknown Facility

Birmingham, Alabama, 35294, United States

Location

Unknown Facility

Scottsdale, Arizona, 85258, United States

Location

Unknown Facility

Miami, Florida, 33136, United States

Location

Unknown Facility

Atlanta, Georgia, 30322, United States

Location

Unknown Facility

Atlanta, Georgia, 30341, United States

Location

Unknown Facility

Lafayette, Indiana, 47905, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Lymphoma; Neoplasms; Endometrial Neoplasms

Interventions

Miransertib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2011
• First Posted: November 17, 2011
• Study Start: November 1, 2011
• Primary Completion: July 6, 2017
• Study Completion: August 7, 2017
• Last Updated: October 23, 2017

Record last verified: 2017-10

Locations

US (7)