Clinical Trials /

CYP17 Lyase and Androgen Receptor Inhibitor Treatment With Seviteronel Trial (INO-VT-464-006; NCT02580448)

NCT02580448

Description:

The goal of this clinical study is to determine the safety, pharmacokinetics, pharmacodynamics and efficacy and activity of seviteronel, a lyase-selective inhibitor of CYP17, in patients with advanced breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

A Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of <span class="go-doc-concept go-doc-intervention">VT-464</span> in Patients With Advanced <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: A Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of VT-464 in Patients With Advanced Breast Cancer
  • Official Title: A Phase 1/2 Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of VT-464 in Patients With Advanced Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02580448

    ORG ID: INO-VT-464-CL-006

    Trial Conditions

    Cancer of the Breast

    Breast Cancer

    Advanced Breast Cancer

    Metastatic Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    VT-464; given orally once daily in 28 day cycles AR (+) TNBC, ER (+) HER2 BC

    Trial Purpose

    The goal of this clinical study is to determine the safety, tolerability, pharmacokinetics
    and activity of VT-464, a lyase-selective inhibitor of CYP17, in patients with advanced
    breast cancer.

    Detailed Description

    This is a non-randomized, open-label, Phase 1/2 trial of VT-464 in patients with AR (+) TNBC
    or ER (+)/HER2 normal unresectable locally advanced MBC. There will be a dose confirmation
    Phase 1 portion of the study to establish the recommended Phase 2 dose. Phase 2 will be an
    open-label, multi-center study and divided into parallel cohorts: AR (+) TNBC and ER (+) BC
    patients at the RP2D confirmed/established in Phase 1.

    Trial Arms

    Name Type Description Interventions
    AR (+) TNBC Experimental Triple Negative Breast Cancer (TNBC) Patients VT-464 given orally once daily in 28 day cycles. VT-464; given orally once daily in 28 day cycles
    ER (+) HER2 BC Experimental ER (+) HER2 normal breast cancer VT-464 given orally once daily in 28 day cycles VT-464; given orally once daily in 28 day cycles

    Eligibility Criteria

    Inclusion Criteria:

    1. Patients must have documented histological or cytological evidence of invasive cancer
    of the breast. Measureable disease is not required.

    2. Phase 1 patients must have TNBC or ER(+) HER2 normal breast cancer and Phase 2
    patients must have AR(+) TNBC or ER(+) HER2 normal breast cancer

    - ER(+) is defined as positive if 1% by IHC

    - ER/PgR(-) is defined as negative if 0% by IHC

    - HER2 normal is defined as IHC 0-1+ or IHC 2+(and FISH<2), or FISH < 2.0

    - AR(+) is defined as 1% by IHC. The assessment of AR expression may have been
    performed any time in the past. Enrollment may be based on local pathology
    findings with subsequent review of AR expression by central pathology to
    determine if the patient will be considered evaluable for Phase 2. For patients
    without known AR status in Phase 2, AR assessment will be performed as a
    pre-screening test following the signing of a separate non-therapeutic informed
    consent.

    3. Patients with ER(+)/HER2 normal tumors must be post-menopausal defined as cessation
    of regular menses for at least 12 consecutive months with no alternative pathological
    or physiological cause, and have a serum FSH level within the laboratory's reference
    range for postmenopausal females that are 60 years old. Ovarian suppression with a
    LH-RH agonist to achieve cessation of regular menses is allowed on study.

    4. Patients with ER(+)/HER2 normal tumors must have progression of disease following 1
    prior line of endocrine therapy. Progression of disease within 6 months of adjuvant
    endocrine therapy will be considered 1 line of prior endocrine therapy.

    5. Availability of a representative, formalin-fixed, paraffin-embedded, tumor specimen
    that enables the definitive diagnosis of breast cancer with adequate viable tumor
    cells in a tissue block (preferred) or 10 (20 preferred) freshly cut, unstained,
    serial slides and the associated pathology report are required prior to enrollment
    (All Phase 2 patients and Phase 1 patients to be considered part of the Phase 2
    evaluable population).

    6. Patients must be female and 18 years of age

    7. ECOG PS of 0 or 1

    8. Patients must have adequate hematopoietic function as evidenced by:

    - WBC 3,000/l

    - ANC 1,500/l

    - Platelet count 100,000/l

    - HGB 10 g/dl and not transfusion dependent

    9. Patients must have adequate hepatic function as evidenced by:

    - AST/ALT levels 3X the ULN

    - Bilirubin levels of 2.0 mg/dl

    10. Patients must have adequate renal function as evidenced by a serum creatinine of
    2.0 mg/dl.

    11. Patients must have K+ >3.5 mEq/l.

    12. Women of child-bearing potential must have a negative serum or urine pregnancy test
    within 72 hours of Cycle 1 Day 1. Female patients who are not of childbearing
    potential meet at least one of the following criteria:

    - Have undergone a documented hysterectomy and/or bilateral oophorectomy,

    - Have medically confirmed ovarian failure, or

    - Achieved post-menopausal status, defined as cessation of regular menses for at
    least 12 consecutive months with no alternative pathological or physiological
    cause, and have a serum FSH level within the laboratory's reference range for
    postmenopausal females that are < 60 years old. Ovarian suppression with a LH-RH
    agonist to achieve cessation of regular menses is allowed on study.

    13. Women of child-bearing potential must agree to use two highly effective methods of
    contraception throughout the study and for at least 30 days after the last dose of
    VT-464. Highly effective methods of contraception are:

    - Established use of oral, inserted, injected or implanted hormonal methods of
    contraception is allowed provided the patient plans to remain on the same
    treatment throughout the entire study and has been using that hormonal
    contraceptive for an adequate period of time to ensure effectiveness.

    - Correctly placed copper-containing intrauterine device (IUD)

    - Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream,
    or suppository).

    - Bilateral tubal ligation or bilateral salpingectomy or bilateral tubal occlusive
    procedure (provided that occlusion has been confirmed in accordance with the
    device's label).

    14. Patients or their legal representatives must be willing and able to provide written
    informed consent.

    Exclusion Criteria:

    1. Patients who require pharmacological or replacement doses of systemic corticosteroids
    or who have received systemic corticosteroids within 7 days of study drug initiation.

    2. Patients who have received any investigational agent within 5 half-lives of the agent
    in question; if the half-life is not known, within 28 days of study entry.

    3. Patients who have received anti-androgens within 4 weeks of study entry.

    4. Patients who have received palliative radiotherapy within 4 weeks of study entry.

    5. Patients with symptomatic CNS metastases from breast cancer

    6. Patients with a history of adrenal insufficiency. Patients receiving systemic
    corticosteroids greater than 2-weeks in duration within 6 months of study entry must
    have a lack of adrenal insufficiency as evidenced by a morning plasma cortisol
    concentration of 500 nmol/l or a plasma cortisol response to an ACTH stimulation
    test that is deemed clinical normal.

    7. Patients with a history of another invasive malignancy within the last 3 years.

    8. Patients with a mean QTc interval of > 470 msec following 3 ECGs 5 minutes apart.

    9. History of clinically significant cardiac arrhythmias (e.g., ventricular tachycardia,
    ventricular fibrillation, atrial fibrillation with rapid ventricular response,
    torsades de pointes, second degree or third degree atrioventricular heart block
    without a permanent pacemaker in place).

    10. Patients with bone metastases who have initiated denosumab or bisphosphonate therapy
    within 28 days of Cycle 1 Day 1.

    11. Patients with any intercurrent conditions that could preclude their participation in
    the study, pose an undue medical hazard, or which could interfere with the
    interpretation of the study results

    12. Patients who have known active HIV, Hepatitis B, or Hepatitis C infections.

    13. Patients with any other condition which in the opinion of the investigator would
    preclude participation in the study.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Phase 1: Maximum tolerated dose of VT-464 in women with unresectable locally or advanced or metastatic breast cancer

    Phase 2: CBRC16 for patients with androgen receptor (AR) positive TNBC (cohort 1) in their respective evaluable populations

    Phase 2: CBR24 for patients with ER(+)BC (cohort 2) in their respective evaluable populations

    Secondary Outcome Measures

    Pharmacokinetics of VT-464 in the ITT population

    Pharmacokinetics of VT-464 in the ITT population

    Efficacy of VT-464 as measured by overall response rate based on RECIST 1.1

    Efficacy of VT-464 as measured by progression free survival

    Trial Keywords

    Breast Cancer

    Breast

    Advanced Breast Cancer

    Metastatic Breast Cancer

    CYP17