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CYP17 Lyase and Androgen Receptor Inhibitor Treatment With Seviteronel Trial (INO-VT-464-006; NCT02580448) (CLARITY-01)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Innocrin Pharmaceutical
Sponsor:
Information provided by (Responsible Party):
Innocrin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT02580448
First received: October 7, 2015
Last updated: April 25, 2017
Last verified: April 2017
  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.

Condition Intervention Phase
Cancer of the Breast
Breast Cancer
Advanced Breast Cancer
Metastatic Breast Cancer
Male Breast Cancer
Triple Negative Breast Cancer
ER+ Breast Cancer
Drug: Female AR(+) TNBC Enzalutamide Naïve
Drug: Female ER(+) BC Patients
Drug: Male ER(+) BC Patients
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Innocrin Pharmaceutical:

Primary Outcome Measures:
  • Describe the dose-limiting adverse events and determination of the maximum-tolerated dose of VT-464 [ Time Frame: Duration of Study ]
    The maximum tolerated dose (MTD) is defined as the highest dose level with Maximum tolerated dose is defined as the highest level dose with DLT in no more than 1 out of 6 patients


Secondary Outcome Measures:
  • Pharmacokinetics of VT-464 in the ITT population [ Time Frame: At least monthly over the first eight 28-day cycles ]
    Area under the curve concentration verses time curve and Peak Plasma Concentration

  • Efficacy of VT-464 as measured by overall response rate based on RECIST 1.1 [ Time Frame: At least monthly over the first eight 28-day cycles ]
    Response and progression will be evaluated using the international criteria proposed by Response Evaluation Criteria in Solid Tumors (RECIST) committee. Changes in only the largest diameter of the tumor lesion are used in RECIST 1.1. Evaluation will occur every 2 cycles for the first 12 months and then every 3 cycles thereafter.

  • Efficacy of VT-464 as measured by progression free survival [ Time Frame: At least monthly over the first eight 28-day cycles ]
    Response and progression will be evaluated using the international criteria proposed by Response Evaluation Criteria in Solid Tumors (RECIST) committee. Changes in only the largest diameter of the tumor lesion are used in RECIST 1.1. Evaluation will occur every 2 cycles for the first 12 months and then every 3 cycles thereafter.

  • Estimate efficacy of VT-464 as measured by clinical benefit rate at 16 weeks (CBR16) for patients with TNBC and clinical benefit rate at 24 weeks (CBR24) for patients with ER(+) BC in Phase 1 study population. [ Time Frame: Duration of the study ]
    Clinical Benefit Rate will be assessed at 16 weeks for TNBC patients and at 24 weeks for ER+ patients


Estimated Enrollment: 175
Study Start Date: August 2015
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Female AR(+) TNBC Enzalutamide Naïve
Female AR(+) TNBC Enzalutamide Naïve Patients
Drug: Female AR(+) TNBC Enzalutamide Naïve
VT-464 given daily with evening meal in 28 day cycles
Experimental: Female ER(+) BC Patients
Female ER(+) BC Patients
Drug: Female ER(+) BC Patients
VT-464 given daily with evening meal in 28 day cycles
Other Name: Female ER+ Breast Cancer Patients
Experimental: Male ER(+) BC Patients
Male ER(+) BC Patients
Drug: Male ER(+) BC Patients
VT-464 given daily with evening meal in 28 day cycles
Other Name: Men with ER+ 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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 positive 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 less than 2), or FISH less than 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. Female 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 LHRH agonist or antagonists to achieve cessation of regular menses is allowed on study. Male patients with ER(+)/HER2 normal tumors must be undergoing gonadal suppression using LHRH agonists or antagonists prior to dosing with VT-464 and continue with the LHRH agonist or antagonist for the duration of the study.
  4. Patients with ER(+)/HER2 normal tumors must have progression of disease following at least 1 prior line of endocrine therapy. Progression of disease within 6 months of adjuvant endocrine therapy will be considered a line of prior endocrine therapy. Patients in the TNBC - Enzalutamide Treated Cohort (Cohort 2) must have received prior enzalutamide for breast cancer.
  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 ≥ 18 years of age
  7. ECOG PS of 0 or 1
  8. Patients must have adequate hematopoietic function as evidenced by:

    • WBC ≥ 3,000/μl
    • ANC ≥ 1,500/μl
    • Platelet count ≥ 100,000/μl
    • 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 LHRH agonist to achieve cessation of regular menses is allowed on study.
  13. Women of child-bearing potential and men who have partners 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 for women and 90 days after the last dose of VT-464 for men. Men must also agree to not donate sperm through 90 days following the last dose of VT-464. For men, one form must be a male condom. 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).
    • Vasectomy
  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 who have received any other therapeutic treatment for breast cancer within 2 weeks of study entry, except for LHRH agonists or antagonists in patients undergoing ovarian suppression enrolled in the Female ER(+) BC cohort and patients undergoing gonadal suppression enrolled in the Male ER(+) BC cohort.
  6. Patients with symptomatic CNS metastases from breast cancer
  7. 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.
  8. Patients with a history of another invasive malignancy within the last 3 years.
  9. Patients with a QTcF interval of >470 msec on the first of the triplicate Screening ECGs; if the first ECG QTcF interval is >470 msec, then the mean QTcF of the triplicate Screening ECGs can be used and if the mean is <470 msec, the patient may be enrolled.
  10. History of clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, atrial fibrillation with rapid ventricular response, torsades de pointes, second degree orthird degree atrioventricular heart block without a permanent pacemaker in place).
  11. Class III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
  12. Patients with bone metastases who have initiated denosumab or bisphosphonate therapy within 28 days of Cycle 1 Day 1.
  13. 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
  14. Patients with a history of seizure within the past 2 years or those who require prophylactic antiseizure medications are excluded.
  15. History of loss of consciousness or transient ischemic attack within 12 months before study drug initiation.
  16. Patients who have known active HIV, Hepatitis B, or Hepatitis C infections.
  17. Patients with any other condition which in the opinion of the investigator would preclude participation in the study.
  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: NCT02580448

Contacts
Contact: Keishea Williams 919-799-2037 kwilliams@innocrinpharma.com
Contact: Tess Ferrer, BSN 919-695-9614 tferrer@innocrinpharma.com

  Show 31 Study Locations
Sponsors and Collaborators
Innocrin Pharmaceutical
Investigators
Study Chair: Keishea Williams Sponsor GmbH
  More Information

Responsible Party: Innocrin Pharmaceutical
ClinicalTrials.gov Identifier: NCT02580448     History of Changes
Other Study ID Numbers: INO-VT-464-CL-006
Study First Received: October 7, 2015
Last Updated: April 25, 2017

Keywords provided by Innocrin Pharmaceutical:
Breast Cancer
Breast
Advanced Breast Cancer
Metastatic Breast Cancer
CYP17
Male Breast Cancer
Triple Negative Cancer
ER+ Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on April 26, 2017