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Solid TumorsPhase 1NCT02476955

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

A Phase 1 study testing ARQ 092 + carboplatin + paclitaxel (Closed), ARQ 092 + paclitaxel (Closed) and ARQ 092 + anastrozole in people with Solid Tumors and Ovarian Cancer, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Solid Tumors, Ovarian Cancer, Endometrial Cancer
What is being tested?
ARQ 092 + carboplatin + paclitaxel (Closed), ARQ 092 + paclitaxel (Closed) and ARQ 092 + anastrozole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
5 sitesUnited States
Study dates
9 Jun 2015to 7 May 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent form
  • 18 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
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  • 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
  • Platelet count (Plt) ≥ 100 x 109/L
  • Hemoglobin (Hb) ≥ 8 g/dL
  • Renal
  • 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
  • Hepatic
  • 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
  • Metabolic - Glycated hemoglobin (HbA1c) ≤ 8%
  • If a subject is currently receiving bisphosphonates or denosumab, the subject must have received the bisphosphonates or denosumab for at least four weeks before starting study treatment. Initiation of bisphosphonates or denosumab during the study may be allowed provided the subject completes the first cycle of treatment without any DLT and the Investigator rules out tumor progression.
  • 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 (3 months after the last dose of ARQ 092 or anastrozole, whichever is longer)

Who cannot join

  • 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.
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  • 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)
  • History of Type 1 or 2 diabetes mellitus requiring regular medication (other than oral hypoglycemic agents including metformin) or fasting glucose ≥ 160 mg/dL
  • Significant gastrointestinal disorder(s), that could in the opinion of the Investigator, interfere with the absorption, metabolism, or excretion of ARQ 092 (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
  • Previous malignancy within 2 years of the first dose of study drugs, except tumors totally resected and/or not requiring therapy
  • Concurrent uncontrolled illness not related to cancer, including but not limited to:
  • Ongoing or active infection, including human immunodeficiency virus (HIV), hepatitis B (HBV) (hepatitis B surface antigen [HBsAg] positive; subjects with documented laboratory evidence of HBV clearance may be enrolled) or hepatitis C (HCV) (positive HCV antibody), or bleeding
  • Psychiatric illness, substance abuse, and/or social situation that would limit compliance with study requirements
  • Blood transfusion within 5 days of the blood draw being used to confirm eligibility
  • Pregnant or breastfeeding

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Study site

    Grand Rapids, Michigan, 49503

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Study site

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: An Open-label Phase 1b Study of ARQ 092 in Combination With Other Antineoplastic Agents in Subjects With Selected Solid Tumors

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

Read the detailed description

This is an open-label Phase 1b, dose escalation study of oral ARQ 092 administered in combination with carboplatin plus paclitaxel (Carboplatin Plus Paclitaxel Arm) or in combination with paclitaxel alone (Paclitaxel Arm), in subjects with advanced, inoperable metastatic and/or recurrent solid tumors, or in combination with anastrozole (Anastrozole Arm) in subjects with ovarian or endometrial cancer.

Enrollment in the Carboplatin plus Paclitaxel Arm and Paclitaxel Alone Arm is now closed. Enrollment in the Expansion Cohort for the Anastrozole Arm continues for patients with Endometrial cancer.

Being tested
ARQ 092 + carboplatin + paclitaxel (Closed), ARQ 092 + paclitaxel (Closed), ARQ 092 + anastrozole
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
Medical subject headings
Ovarian Neoplasms, Endometrial Neoplasms, Uterine Cervical Neoplasms, Triple Negative Breast Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ARQ 092 + carboplatin + paclitaxel (Closed)Drug

    Also called cis-Diammine, Paraplatin, Taxol, Abraxane

    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.

  • ARQ 092 + paclitaxel (Closed)Drug

    Also called Taxol, Abraxane

    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.

  • ARQ 092 + anastrozoleDrug

    Also called Arimidex

    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.

Study groups in NCT02476955
Study groupRoleWhat they receive
ARQ 092 + anastrozoleExperimentalARQ 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.
Receives: Drug: ARQ 092 + carboplatin + paclitaxel (Closed); Drug: ARQ 092 + paclitaxel (Closed); Drug: ARQ 092 + anastrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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

    Measured: 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.

  3. 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

    Measured: 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.

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

    DoR will be assessed as a measure of efficacy

    Measured: 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)

  1. Peak plasma concentration (Cmax)

    Measured: 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).

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

    Measured: 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).

  3. Half-life of ARQ 092

    Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jun 2015 (estimated)
  2. Study start9 Jun 2015
  3. Primary completion7 May 2019
  4. Study completion7 May 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02476955
Sponsor's protocol ID
7075-001
Other IDs
ARQ 092-102
Status last verified
Sep 2020
First submitted
10 Jun 2015
Last updated
30 Sep 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ARQ 092 + carboplatin + paclitaxel (Closed), ARQ 092 + paclitaxel (Closed) and ARQ 092 + anastrozole in people with Solid Tumors and Ovarian Cancer, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of treatment emergent adverse events (TEAEs) as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (time frame: Assessed at each scheduled visit up to treatment discontinuation + 30 days with an estimated treatment duration of 3 to 24 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02476955.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2020; AzTrials last refreshed its copy on 6 Nov 2026.

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