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Trial record 1 of 1 for:    ARQ 751
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Phase 1 Study of ARQ 751 in Solid Tumors With AKT1, 2, 3 Genetic Alterations, Activating PI3K Mutations or PTEN-null

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by ArQule
Sponsor:
Information provided by (Responsible Party):
ArQule
ClinicalTrials.gov Identifier:
NCT02761694
First received: April 29, 2016
Last updated: March 14, 2017
Last verified: March 2017
  Purpose
An open-label, Phase 1, dose escalation study of ARQ 751 in subjects with advanced solid tumors with AKT1, 2, 3 genetic alterations, activating PI3K mutations or PTEN-null.

Condition Intervention Phase
Cancer
Solid Tumors
Drug: ARQ 751
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Study of ARQ 751 in Adult Subjects With Advanced Solid Tumors With AKT1, 2, 3 Genetic Alterations, Activating PI3K Mutations or PTEN-null

Resource links provided by NLM:


Further study details as provided by ArQule:

Primary Outcome Measures:
  • Incidence of adverse events graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) guidelines v4.03 [ Time Frame: Up to 24 weeks ]
    The incidence of adverse events will be assessed as a measure of the safety and tolerability profile of ARQ 751


Secondary Outcome Measures:
  • Assess the peak plasma concentration (Cmax) of the pharmacokinetic (PK) profile of ARQ 751 [ Time Frame: Cycle 1 Day 1 (C1D1) (each cycle is 28 days) (time [t]=0,1,2,4,6,8,10,12 hours [h]), C1D2, D8, and D15 (t=0), C1D22 (t=0,1,2,4,6,8,10,12 h), C1D23, C2D1, and C2D15 (t=0) ]
  • Assess the area under the plasma concentration vs. time curve (AUC) of the pharmacokinetic (PK) profile of ARQ 751 [ Time Frame: Cycle 1 Day 1 (C1D1) (each cycle is 28 days) (time [t]=0,1,2,4,6,8,10,12 hours [h]), C1D2, D8, and D15 (t=0), C1D22 (t=0,1,2,4,6,8,10,12 h), C1D23, C2D1, and C2D15 (t=0) ]
  • Assess the half life of ARQ 751 of the pharmacokinetic (PK) profile of ARQ 751 [ Time Frame: Cycle 1 Day 1 (C1D1) (each cycle is 28 days) (time [t]=0,1,2,4,6,8,10,12 hours [h]), C1D2, D8, and D15 (t=0), C1D22 (t=0,1,2,4,6,8,10,12 h), C1D23, C2D1, and C2D15 (t=0) ]
  • Assess paired tumor biopsies to determine pharmacodynamic activity of ARQ 751 [ Time Frame: Tumor samples are assessed at Baseline and at any timepoint between Cycle 1 Day 15 (C1D15) and C2D1 (each cycle is 28 days). ]
  • Assess changes in serum glucose and insulin levels to determine pharmacodynamic activity of ARQ 751 [ Time Frame: Blood samples are collected on Day 1 of Cycles 1 and 2 (each cycle is 28 days) and at the End of Treatment visit, which may occur at up to 24 weeks after the first dose ]
  • Determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of ARQ 751 [ Time Frame: Up to the first 28 days (1 cycle) of therapy ]
    MTD is defined as the dose level at which no more than one out of six subjects has an observable dose limiting toxicity (DLT)

  • Evaluate tumor response assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 after treatment with ARQ 751 [ Time Frame: Tumor assessments will be performed at Baseline, every eight weeks (e.g., Cycle 3 Day 1, Cycle 5 Day 1, etc), and at the End of Treatment visit, which may occur at up to 24 weeks after the first dose ]

Estimated Enrollment: 100
Study Start Date: June 2016
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARQ 751
Subjects will receive ARQ 751 orally at the dose level and administration schedule specified for their respective dose cohort on a 28 day cycle. Subjects will receive treatment with ARQ 751 until unacceptable toxicity, disease progression (clinical or radiological), or another discontinuation criterion is met. It is expected that most subjects will receive between one and six cycles of ARQ 751 for a treatment period of 4 to 24 weeks.
Drug: ARQ 751
Subjects will receive ARQ 751 orally at the dose level and administration schedule specified for their respective dose cohort on a 28 day schedule.

Detailed Description:
This is an open-label, Phase 1, dose escalation study of ARQ 751 administered orally to subjects with advanced solid tumors with AKT1, 2, 3 genetic alterations, activating PI3K mutations or PTEN-null.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed written informed consent granted prior to initiation of any study-specific procedures
  2. 18 years of age and older
  3. Histologically or cytologically documented locally advanced, inoperable or metastatic solid tumors with documented AKT1, 2, 3 genetic alterations, activating PI3K mutations or PTEN null
  4. Failure to respond to standard therapy, or for whom standard or curative therapy does not exist, or is not tolerable.

    a. Subjects enrolled in the Expanded Cohort should have no more than 3 prior systemic regimens with confirmed disease progression. If the subject is refractory or has disease progression within 6 months of the adjuvant treatment, then the previous treatment should be considered as the line of treatment rather than an adjuvant therapy.

  5. Measurable disease
  6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
  7. Archival tissue samples and/or fresh tumor biopsy samples:

    1. Subjects should agree to provide archival and/or fresh tumor biopsy samples
    2. Archival tumor samples should be collected for all enrolled subjects; if archival tissue samples are not available, a recent core needle biopsy should be collected
    3. Paired, pre- and post-treatment, tumor biopsy is optional for subjects enrolled in the Dose Escalation and Food-effect cohorts
    4. Paired tumor biopsy is mandatory for all subjects enrolled in the Expanded cohort; subjects should agree to and be eligible for paired tumor biopsy
  8. 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 ARQ 751:

    a. Hematological i. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L ii. Platelet count (Plt) ≥ 100 x 109/L iii. Hemoglobin (Hb) ≥ 9 g/dL iv. International normalized ratio (INR) 0.8 to upper limit of normal (ULN) or ≤ 3 for subjects receiving anticoagulant therapy such as Coumadin or heparin b. Renal i. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with serum creatinine levels > 1.5 x institutional ULN c. Hepatic i. Total bilirubin ≤ 1.5 x ULN ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN or ≤ 5 x ULN for subjects with known liver metastases d. Metabolic i. Glycated hemoglobin (HbA1c) ≤ 8%

  9. If a subject is currently receiving bisphosphonates, the subject must have received the bisphosphonates for at least four weeks prior to the first dose of ARQ 751.

    a. Initiation of bisphosphonates during the study may be allowed provided the subject completes the first cycle of treatment without any dose limiting toxicity (DLT) and the Investigator rules out tumor progression.

  10. Male or female subjects of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after the last dose of ARQ 751.
  11. Women of childbearing potential must have a negative serum pregnancy test during the Screening Period and within 48 hours of the first dose of ARQ 751. "Women of childbearing potential" is defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months prior to the first dose of ARQ 751.

Exclusion Criteria:

  1. Anti-cancer therapy, such as chemotherapy, immunotherapy, targeted, and hormonal/endocrine therapy, or investigational agents within four weeks prior to administration of the first dose of study drug (two weeks for orally administered drugs and six weeks for nitrosoureas, mitomycin C, or bevacizumab)

    1. To be eligible for study treatment, toxicity from prior treatment must recover to Grade ≤ 1, except for alopecia
    2. 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
    3. Concurrent standard long-term anticancer hormonal therapy with drugs including, but not limited to, selective estrogen receptor modulators or Gonadotropin-releasing hormone (GnRH) analogs if started at least six months before the first dose of ARQ 751 is allowed
  2. Radiation therapy within four weeks prior to administration of the first dose of ARQ 751

    1. To be eligible for study treatment, radiation therapy-related toxicity must recover to Grade ≤ 1 prior to administration of the first dose of ARQ 751.
    2. Concurrent palliative radiotherapy for local pain-control may be allowed provided the subject completes the first cycle of treatment, does not meet criteria of progressive disease, and treated lesions will not be included in the target/non-target lesion assessment.
  3. Major surgical procedure within four weeks prior to administration of the first dose of ARQ 751

    a. To be eligible for the study treatment, all surgical wounds must be fully healed and any surgery-related adverse events must recover to Grade ≤ 1.

  4. Previous treatment with AKT inhibitors (e.g., ARQ 092, MK-2206, GSK2141795, AZD5363)
  5. Unable or unwilling to swallow the complete daily dose of ARQ 751
  6. A corrected QT interval (QTc) ≥ 480 msec using the Fridericia's formula (QTcF)
  7. History of Type 1 or 2 diabetes mellitus requiring regular medication (other than oral hypoglycemic agents) or fasting glucose ≥ 160 mg/dL at the Pre-Study visit
  8. Significant gastrointestinal (GI) disorder(s) that could, in the opinion of the Investigator, interfere with the absorption, metabolism, or excretion of ARQ 751 (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
  9. Known active CNS metastases and/or carcinomatous meningitis

    a. To be eligible for the study treatment, subjects must have stable disease ≥ 1 month, 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.

  10. History of myocardial infarction (MI) or New York Heart Association (NYHA) Class II-IV congestive heart failure within 6 months of the administration of the first dose of ARQ 751 (MI occurring > 6 months of the first dose of ARQ 751 will be permitted); Grade 2 or worse conduction defect (e.g., right or left bundle branch block)
  11. Concurrent severe uncontrolled illness not related to cancer and social situation that would limit compliance with study requirements, including but not limited to:

    1. Psychiatric illness, substance abuse
    2. Ongoing or active known infection, including human immunodeficiency virus (HIV) infection
  12. Active or history of other malignancy other than the current cancer within 2 years of the first dose of ARQ 751, with the exception of carcinoma in-situ of the cervix, basal cell carcinoma, and superficial bladder tumors curatively treated
  13. Blood transfusion or administration of growth factors within 5 days prior to a blood draw being used to confirm eligibility
  14. Pregnant or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02761694

Contacts
Contact: ArQule, Inc. 781-994-0300 ClinicalTrials@arqule.com

Locations
United States, Nevada
Active, not recruiting
Las Vegas, Nevada, United States, 89169
United States, Texas
Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
ArQule
  More Information

Responsible Party: ArQule
ClinicalTrials.gov Identifier: NCT02761694     History of Changes
Other Study ID Numbers: ARQ 751-101
Study First Received: April 29, 2016
Last Updated: March 14, 2017

Keywords provided by ArQule:
AKT1
AKT2
AKT3
PI3K
PTEN-null
solid tumors
cancer
ARQ 751
ArQule

ClinicalTrials.gov processed this record on April 28, 2017