Open-label Phase 1b Study of ARQ 092 in Combination With Anastrozole

NCT02476955 | Terminated Phase 1

• 2 other identifiers: 7075-001ARQ 092-102
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 5

Brief Summary

An Open-label Phase 1b Study of ARQ 092 in Combination with other Antineoplastic Agents in Subjects with Selected Solid Tumors

Conditions

Solid Tumors; Ovarian Cancer; Endometrial Cancer

Keywords

ARQ 092; Carboplatin; Paclitaxel; AKT inhibitor in combination therapy; Targeted therapy; Molecular therapy; Tyrosine kinase inhibitor (TKI); Receptor tyrosine kinase (RTK); Biomarkers; Phase 1 - Phase I; Solid tumors; Metastatic solid tumors; Recurrent solid tumors; Ovarian cancer; Endometrial cancer; Cervical cancer; Triple-negative breast cancer; AKT kinases; AKT pathway; AKT signaling; AKT inhibitor; AKT pan inhibitor; Chemotherapy; PI3K/AKT/mTOR signaling pathway; AKT1; AKT2; AKT3; Phase I Clinical Trial; Clinical oncology; Tumor; AKT1 inhibitor; AKT2 inhibitor; AKT3 inhibitor; AKT1 mutation; AKT2 mutation; AKT3 mutation; AKT1 amplification; AKT2 amplification; AKT3 amplification; Anastrozole; Estrogen receptor positive; PIK3CA mutation

Outcome Measures

Primary Outcomes (4)

• Number of treatment emergent adverse events (TEAEs) as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  The incidence of adverse events will be assessed as a measure of the safety and tolerability profile of ARQ 092

  Assessed at each scheduled visit up to treatment discontinuation + 30 days with an estimated treatment duration of 3 to 24 weeks

• Overall Response Rate (ORR) based on central review of tumor measurement using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  ORR will be assessed as a measure of efficacy

  Baseline and every 2 cycles (8 weeks) after the first dose of ARQ 092 during the first 6 cycles (24 weeks) of treatment, and every 3 cycles (12 weeks) thereafter or as clinically indicated, and at the End of Treatment.

• Progression Free Survival (PFS) based on central review of tumor measurement using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  PFS will be assessed as a measure of efficacy

  Baseline and every 2 cycles (8 weeks) after the first dose of ARQ 092 during the first 6 cycles (24 weeks) of treatment, and every 3 cycles (12 weeks) thereafter or as clinically indicated, and at the End of Treatment.

• Duration of Response (DoR) based on central review of tumor measurement

  DoR will be assessed as a measure of efficacy

  Baseline and every 2 cycles (8 weeks) after the first dose of ARQ 092 during the first 6 cycles (24 weeks) of treatment, and every 3 cycles (12 weeks) thereafter or as clinically indicated, and at the End of Treatment.

Secondary Outcomes (3)

• Peak plasma concentration (Cmax)

  During Cycle 1, Day 1 and Cycle 2, Day 1 of treatment (t=0, 2, 4, 6, 8, 10, 12 hours post ARQ 092 dose). And at Cycle 1, Day 8, Day 15, and Day 22 (t = pre-dose ARQ 092 dose).

• Area under the plasma concentration vs. time curve (AUC)

  During Cycle 1, Day 1 and Cycle 2, Day 1 of treatment (t=0, 2, 4, 6, 8, 10, 12 hours post ARQ 092 dose). And at Cycle 1, Day 8, Day 15, and Day 22 (t = pre-dose ARQ 092 dose).

• Half-life of ARQ 092

  During Cycle 1, Day 1 and Cycle 2, Day 1 of treatment (t=0, 2, 4, 6, 8, 10, 12 hours post ARQ 092 dose). And at Cycle 1, Day 8, Day 15, and Day 22 (t = pre-dose ARQ 092 dose).

Study Arms (1)

ARQ 092 + anastrozole

EXPERIMENTAL

ARQ 092 will be administered orally at 150 milligrams (mg) every day (QD), 5 days on/9 days off of a 28 day cycle in combination with anastrozole which will be administered orally at 1 mg QD continuously. The combination treatment will continue until progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria is documented.

Drug: ARQ 092 + carboplatin + paclitaxel (Closed); Drug: ARQ 092 + paclitaxel (Closed); Drug: ARQ 092 + anastrozole

Interventions

ARQ 092 + carboplatin + paclitaxel (Closed) DRUG

Subjects will receive ARQ 092 orally at dose levels specified for their respective dose cohorts plus carboplatin (AUC6, intravenously, Day 1) plus paclitaxel (175 mg/m2, intravenously, Day 1) on a 21-day schedule.

Also known as: cis-Diammine, Paraplatin, Taxol, Abraxane

ARQ 092 + anastrozole

ARQ 092 + paclitaxel (Closed) DRUG

ARQ 092 will be administered orally at 200 mg twice a day (BID) weekly (Cohort 1P) of a 28-day cycle in combination with an intravenous (IV) infusion of paclitaxel (80 mg/m2). ARQ 092 will be administered once a week on Day 1, Day 8, Day 15, and Day 22 of each 28-day cycle; paclitaxel will be administered once a week on Day 1, Day 8, and Day 15 for three consecutive weeks followed by one week off of each 28-day cycle.

Also known as: Taxol, Abraxane

ARQ 092 + anastrozole

ARQ 092 + anastrozole DRUG

ARQ 092 will be administered orally at 150 mg QD, 5 days on/9 days of a 28 day cycle in combination with anastrozole which will be administered orally at 1 mg QD continuously.

Also known as: Arimidex

ARQ 092 + anastrozole

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent form
• years of age or older
• Histologically or cytologically confirmed locally advanced, inoperable, or metastatic tumors:
• Subjects with endometrial cancer with:
• Documented/locally determined AKT1, PIK3CA, or PIK3R1 mutations with or without PTEN deficiency
• ER+ status
• Female subjects of child-bearing potential must have a negative serum or urine pregnancy test within 72 hours prior to administration of the first dose of study drug. "Women of childbearing potential" is defined as sexually mature women who have not undergone hysterectomy and/or bilateral oophorectomy, or who have not been naturally postmenopausal for at least 12 consecutive months prior to administration of the first dose of the study drug.
• Measurable or evaluable disease
• Subjects must agree to provide requested amount of archival and/or fresh tissue biopsy samples at baseline for mutational analysis by the Sponsor's central laboratory.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Life expectancy ≥ 12 weeks
• Failure to respond to or refractory to approved/standard therapy; or for whom standard therapy does not exist, or is not tolerable; or for whom approved/standard therapy is not considered to be sufficient or appropriate by the Investigator.
• Adequate organ function as indicated by the following laboratory values. All laboratory tests must be obtained within 7 days prior to the first dose of study treatment:
• Hematological
• \- Absolute neutrophil count (ANC) ≥ 1.0 x 109/L

You may not qualify if:

• Anti-cancer therapy, such as chemotherapy, immunotherapy, targeted and hormonal/endocrine therapy, or investigational agents within five half-lives or two weeks (whichever is shorter) for oral drugs, five half-lives or four weeks (whichever is shorter) for intravenous drugs, and six weeks for nitrosoureas, mitomycin C, or bevacizumab prior to administration of the first dose of study drug
• To be eligible for study treatment, toxicity from prior treatment must recover to Grade ≤ 1, except for alopecia
• Concurrent systemic high-dose corticosteroids when used intermittently in an antiemetic regimen for central nervous system (CNS) metastases management or as a part of the premedication regimen are allowed
• Prior hormonal therapy (including, but not limited to, tamoxifen, megestrol acetate, fulvestrant, and GnRH analogs) for the treatment of recurrent/advanced endometrial cancer are not allowed
• Radiation therapy within four weeks prior to administration of the first dose of study drug
• To be eligible for study treatment, radiation therapy-related toxicity must recover to Grade ≤ 1 prior to administration of the first dose of study drug. Concurrent palliative radiotherapy for local pain-control may be allowed, provided the subject does not meet criteria of progressive disease and treated lesions will not be included in the target/non-target lesion assessment.
• Major surgical procedure within four weeks prior to administration of the first dose of study drug
• To be eligible for study treatment, all surgical wounds must be fully healed and any surgery-related adverse events (AE) must recover to Grade ≤ 1
• Previous treatment with AKT inhibitors (e.g., MK-2206, GSK2141795, AZD5363)
• Contraindications to treatment with anastrozole defined by the Investigator based on institutional Standard of Care (SOC), scientific evidence, expert medical judgment, or published literature
• History of allergic reaction attributed to compound(s) of similar chemical or biologic composition as ARQ 092 or anastrozole
• Unable or unwilling to swallow ARQ 092 or anastrozole
• Known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis
• To be eligible for the study treatment, subjects must have stable disease ≥ 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications
• History of myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association (NYHA) classification within 6 months of the first dose of ARQ 092 (MI that occurred \> 6 months prior to the first dose of ARQ 092 will be permitted)

Sponsors & Collaborators

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

Study Sites (5)

Unknown Facility

Grand Rapids, Michigan, 49503, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms; Uterine Cervical Neoplasms; Triple Negative Breast Neoplasms; Neoplasms

Interventions

Miransertib; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel; Anastrozole

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Uterine Cervical Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

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: June 10, 2015
• First Posted: June 22, 2015
• Study Start: June 9, 2015
• Primary Completion: May 7, 2019
• Study Completion: May 7, 2019
• Last Updated: September 30, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share

Locations

US (5)