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

This study is currently recruiting participants.
Verified October 2017 by ArQule
Sponsor:
ClinicalTrials.gov Identifier:
NCT02476955
First Posted: June 22, 2015
Last Update Posted: October 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
ArQule
  Purpose
An Open-label Phase 1b Study of ARQ 092 in Combination with Carboplatin Plus Paclitaxel, in Combination with Paclitaxel, or in Combination with Anastrozole in Subjects with Selected Solid Tumors

Condition Intervention Phase
Solid Tumors Ovarian Cancer Endometrial Cancer Drug: ARQ 092 + carboplatin + paclitaxel Drug: ARQ 092 + paclitaxel Drug: ARQ 092 + anastrozole Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase 1b Study of ARQ 092 in Combination With Carboplatin Plus Paclitaxel, in Combination With Paclitaxel, or in Combination With Anastrozole in Subjects With Selected Solid Tumors

Resource links provided by NLM:


Further study details as provided by ArQule:

Primary Outcome Measures:
  • 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, in combination with paclitaxel alone, or in combination with anastrozole [ Time Frame: Assessed at each scheduled visit up to treatment discontinuation + 30 days with an estimated treatment duration of 3 to 24 weeks ]

Secondary Outcome Measures:
  • Characterize the pharmacokinetic (PK) profile of ARQ 092 when administered in combination with carboplatin and paclitaxel, in combination with paclitaxel alone, or in combination with anastrozole [ Time Frame: During the first cycle of treatment for each dose level (t=0, 2, 4, 6, 8, 10, 12 hours post ARQ 092 dose) ]
    PK parameters include the peak plasma concentration (Cmax), area under the plasma concentration vs. time curve (AUC), and half-life of ARQ 092

  • Evaluate tumor response assessed by RECIST v1.1 after treatment with ARQ 092 administered in combination with carboplatin and paclitaxel, in combination with paclitaxel alone, or in combination with anastrozole [ Time Frame: Baseline, every 2 cycles for the first 6 cycles, then every 3 cycles thereafter, and the End of Treatment visit ]
  • Evaluate dose limiting toxicity (DLT) graded per CTCAE v4.03 to determine the recommended Phase 2 dosing regimen [ Time Frame: During the first cycle of treatment for each subject ]

Estimated Enrollment: 52
Study Start Date: June 2015
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARQ 092 + carboplatin + paclitaxel

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.

The combination treatment will continue for a maximum of 6 x 21-day cycles followed by single agent therapy with ARQ 092 at the cohort dose level and administration schedule to which the subject was enrolled. Subjects will receive treatment with ARQ 092 until progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria is documented.

Drug: ARQ 092 + carboplatin + paclitaxel
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.
Other Names:
  • cis-Diammine
  • Paraplatin
  • Taxol
  • Abraxane
Experimental: ARQ 092 + paclitaxel
ARQ 092 will be administered orally at 200 mg BID weekly of a 28-day cycle in combination with an 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. 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 + paclitaxel
ARQ 092 will be administered orally at 200 mg BID weekly (Cohort 1P) of a 28-day cycle in combination with an 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.
Other Names:
  • Taxol
  • Abraxane
Experimental: ARQ 092 + anastrozole
ARQ 092 will be administered orally at 200 mg 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 + anastrozole
ARQ 092 will be administered orally at 200 mg QD, 5 days on/9 days off (Cohort 1A) of a 28 day cycle in combination with anastrozole which will be administered orally at 1 mg QD continuously.
Other Name: Arimidex

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.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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 form
  2. 18 years of age or older
  3. Histologically or cytologically confirmed locally advanced, inoperable, or metastatic tumors:

    • Carboplatin Plus Paclitaxel Arm:

    • Subjects with any tumor type (except lung) for which carboplatin plus paclitaxel chemotherapy would be appropriate

      • Paclitaxel Arm:

    • Subjects with any tumor type (except lung) for which paclitaxel chemotherapy would be appropriate

      • Anastrozole Arm:

    • Subjects with ovarian and endometrial cancer with:

      • Documented/locally determined AKT1 or PIK3CA mutation
      • ER+ status
  4. 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.
  5. Measurable or evaluable disease
  6. Subjects must agree to provide archival and/or fresh tissue biopsy samples, if available. Tumor biopsy will be done only if the subject has a lesion for which, in the opinion of the Investigator, a non- or minimally invasive tumor biopsy may be performed.
  7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  8. Life expectancy ≥ 12 weeks
  9. 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.

    • Carboplatin Plus Paclitaxel Arm:

    • Subjects who were previously treated with carboplatin and paclitaxel for locally advanced and/or metastatic disease and who received the last dose of the drug(s) ≥ 12 months prior to the first dose of the study treatment may be enrolled
    • Subjects who were not previously treated with carboplatin and paclitaxel for locally advanced and/or metastatic disease and for whom, in the opinion of the Investigator, this chemotherapy regimen is appropriate may be enrolled

      • Paclitaxel Arm:

    • Subjects who were previously treated with paclitaxel for locally advanced and/or metastatic disease and who in the opinion of the Investigator may benefit from the combination treatment of ARQ 092 and paclitaxel may be enrolled
    • Subjects who were not previously treated with paclitaxel for locally advanced and/or metastatic disease and for whom, in the opinion of the Investigator, this chemotherapy regimen is appropriate may be enrolled
  10. 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) ≥ 1.5 x 109/L (Carboplatin Plus Paclitaxel Arm or Paclitaxel Arm) or ≥ 1.0 x 109/L (Anastrozole Arm)
      • Platelet count (Plt) ≥ 100 x 109/L
      • Hemoglobin (Hb) ≥ 9 g/dL (Carboplatin Plus Paclitaxel Arm or Paclitaxel Arm) or ≥ 8 g/dL (Anastrozole Arm)
    • 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%
  11. 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.)
  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 (six months after the last dose of paclitaxel or 3 months after the last dose of ARQ 092 whichever is longer)

Exclusion Criteria:

  1. Anti-cancer therapy, such as chemotherapy, immunotherapy, targeted and hormonal/endocrine therapy, or investigational agents within two weeks for oral drugs, four weeks 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
    • For subjects enrolled in the Carboplatin Plus Paclitaxel Arm or Paclitaxel Arm, 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 study treatment is allowed
  2. 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.

  3. 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

  4. Previous treatment with AKT inhibitors (e.g., MK-2206, GSK2141795, AZD5363)
  5. Contraindications to treatment with:

    • Carboplatin and/or paclitaxel defined by the Investigator based on the Food and Drug Administration (FDA) approved labeling or institutional standard of care (SOC)
    • Anastrozole defined by the Investigator based on institutional SOC, scientific evidence, expert medical judgment, or published literature
  6. History of allergic reaction attributed to compound(s) of similar chemical or biologic composition as ARQ 092, carboplatin, paclitaxel, or anastrozole
  7. Unable or unwilling to swallow ARQ 092 or anastrozole or comply with chemotherapy regimen
  8. Known active 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

  9. 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)
  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 (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
  12. Previous malignancy within 2 years of the first dose of study drugs, except tumors totally resected and/or not requiring therapy
  13. 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

  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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02476955


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

Locations
United States, Michigan
Completed
Grand Rapids, Michigan, United States, 49503
United States, New York
Recruiting
New York, New York, United States, 10065
United States, Texas
Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
ArQule
  More Information

Responsible Party: ArQule
ClinicalTrials.gov Identifier: NCT02476955     History of Changes
Other Study ID Numbers: ARQ 092-102
First Submitted: June 10, 2015
First Posted: June 22, 2015
Last Update Posted: October 12, 2017
Last Verified: October 2017

Keywords provided by ArQule:
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

Additional relevant MeSH terms:
Ovarian Neoplasms
Endometrial Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Uterine Neoplasms
Uterine Diseases
Paclitaxel
Anastrozole
Albumin-Bound Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists