Open-label Phase 1b Study of ARQ 092 in Combination With Carboplatin Plus Paclitaxel

Condition(s) targeted: Ovarian Cancer; Endometrial Cancer; Cervical Cancer; Breast Cancer Triple Negative

Intervention: ARQ 092 + carboplatin + paclitaxel (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: ArQule

Overall contact:
ArQule, Inc., Phone: 781-994-0300, Email: ClinicalTrials@arqule.com

An Open-label Phase 1b Study of ARQ 092 in Combination with Carboplatin Plus Paclitaxel in Subjects with Selected Solid Tumors

Official title: An Open-label Phase 1b Study of ARQ 092 in Combination With Carboplatin Plus Paclitaxel in Subjects With Selected Solid Tumors

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Adverse events graded by CTCAE v4.03 as a measure of the safety and tolerability profile of ARQ 092 administered in combination with carboplatin and paclitaxel

Secondary outcome:

Characterize the pharmacokinetic (PK) profile of ARQ 092 when administered in combination with carboplatin and paclitaxel

Evaluate tumor response assessed by RECIST v1.1 after treatment with ARQ 092 administered in combination with carboplatin and paclitaxel

Evaluate dose limiting toxicity (DLT) graded per CTCAE v4.03 to determine the recommended Phase 2 dosing regimen

Detailed description: This is an open-label, Phase 1b, dose escalation study of oral ARQ 092 administered in combination with carboplatin and paclitaxel in subjects with advanced, inoperable metastatic and/or recurrent solid tumors.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Signed written informed consent form 2. 18 years of age or older 3. Histologically or cytologically confirmed locally advanced, inoperable, or metastatic tumors 4. Female subjects of child-bearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first dose of study drug 5. Measurable disease 6. Subjects must agree to provide archival and/or fresh tissue biopsy samples, if available 7. ECOG performance status ≤ 2 8. Life expectancy ≥ 12 weeks 9. Failure to respond to standard therapy, or for whom standard therapy does not exist, or is not tolerable 10. Absolute neutrophil count (ANC) ≥ 1. 5 x 109/L Platelet count (Plt) ≥ 100 x 109/L Hemoglobin (Hb) ≥ 9 g/dL Serum creatinine ≤ 1. 5 x upper limit of normal (ULN) or Calculated creatinine clearance ≥ 60 mL/min /1. 73 m2 for subjects with serum creatinine levels > 1. 5 x institutional ULN Total bilirubin ≤ 1. 5 x ULN or Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1. 5 x ULN AST and ALT ≤ 3 x ULN or ≤ 5 x ULN for subjects with known liver metastases HbA1c ≤ 8% 11. If a subject is currently receiving bisphosphonates, the subject must have received the bisphosphonates for at least four weeks before starting study treatment 12. Male or female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during and after the study Exclusion Criteria: 1. Anti-cancer therapy within four weeks prior to administration of the first dose of study drug 2. Radiation therapy within four weeks prior to administration of the first dose of study drug 3. Major surgical procedure within four weeks prior to administration of the first dose of study drug 4. Previous treatment with AKT inhibitors 5. Contraindications to treatment with carboplatin and/or paclitaxel defined by the Investigator based on the FDA approved labeling or institutional SOC 6. History of allergic reaction attributed to compound(s) of similar chemical or biologic composition as ARQ 092 or carboplatin and/or paclitaxel 7. Unable or unwilling to swallow ARQ 092 or comply with chemotherapy regimen 8. Known active CNS metastases and/or carcinomatous meningitis 9. History of myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the NYHA classification within 6 months of the first dose of ARQ 092 10. History of Type 1 or 2 diabetes mellitus requiring regular medication (other than oral hypoglycemic agents including metformin) or fasting glucose ≥ 160 mg/dL 11. Significant gastrointestinal disorder(s), that could in the opinion of the Investigator, interfere with the absorption, metabolism, or excretion of ARQ 092 12. Previous malignancy within 2 years of the first dose of study drugs, except curatively treated non-melanoma skin cancer, carcinoma in-situ of the breast or cervix, superficial bladder tumors 13. Concurrent uncontrolled illness not related to cancer, including but not limited to ongoing or active infection, including HIV, HBV (HbsAg positive; subjects with documented laboratory evidence of HBV clearance may be enrolled) or HCV (positive HCV antibody), or bleeding 14. Psychiatric illness, substance abuse, and/or social situation that would limit compliance with study requirements 15. Blood transfusion within 5 days of the blood draw being used to confirm eligibility 16. Pregnant or breastfeeding

ArQule, Inc., Phone: 781-994-0300, Email: ClinicalTrials@arqule.com

San Antonio, Texas 78229, United States; Recruiting

Starting date: June 2015
Last updated: June 17, 2015