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

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ClinicalTrials.gov Identifier: NCT02580448
Recruitment Status : Active, not recruiting
First Posted : October 20, 2015
Last Update Posted : December 7, 2018
Sponsor:
Information provided by (Responsible Party):
Innocrin Pharmaceutical

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cancer of the Breast Breast Cancer Advanced Breast Cancer Metastatic Breast Cancer Male Breast Cancer Triple Negative Breast Cancer ER+ Breast Cancer Drug: Seviteronel Phase 1 Phase 2

Detailed Description:

This is an open-label, Phase 1/2 study of seviteronel in subjects with TNBC or ER +/HER2 normal unresectable locally advanced breast cancer. Only women will be enrolled in Phase 1 and both men and women enrolled into their respective cohorts in Phase 2. There will be a dose confirmation Phase 1 portion of the study to establish the recommended Phase 2 dose (RP2D) for women with breast cancer using a non-stratified, combined cohort of women with TNBC or ER+ BC. Cohort expansion will occur in Phase 2 at the RP2D confirmed/established in Phase 1 using separate TNBC and ER+ cohorts. The Phase 2 portion of the study is divided into three parallel cohorts:

Cohort 1: Female TNBC Subjects Cohort 2: Female ER+ Subjects Cohort 3: Male ER+ BC or TNBC Subjects


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 175 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Seviteronel in Subjects With Advanced Breast Cancer
Actual Study Start Date : August 2015
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Female Triple Negative Breast Cancer Patients
TNBC Patients - Enrollment is complete in this cohort
Drug: Seviteronel
Seviteronel given daily with evening meal in 28 day cycles

Experimental: Female Estrogen Receptor (+) Breast Cancer Patients
Female ER(+) BC Patients - Enrollment is complete in this cohort
Drug: Seviteronel
Seviteronel given daily with evening meal in 28 day cycles

Experimental: Male Breast Cancer Patients
Locally advanced or metastatic males with BC
Drug: Seviteronel
Seviteronel given daily with evening meal in 28 day cycles




Primary Outcome Measures :
  1. Estimate efficacy of seviteronel as measured by clinical benefit rate at 16 weeks (CBR16) for female subjects with TNBC. [ Time Frame: Duration of Study ]
  2. Estimate efficacy of seviteronel as measured by clinical benefit rate at 24 weeks (CBR24) for female subjects with ER+ BC. [ Time Frame: Duration of Study ]
  3. Estimate efficacy of seviteronel as measured by CBR16 for all male BC subjects. [ Time Frame: Duration of Study ]

Secondary Outcome Measures :
  1. Describe the pharmacokinetics of seviteronel [ Time Frame: At least monthly over the first eight 28-day cycles ]
    Area under the curve concentration verses time curve and Peak Plasma Concentration

  2. Estimate efficacy of seviteronel as measured by the overall response rate (ORR) based on RECIST 1.1 [ Time Frame: At least monthly over the first eight 28-day cycles ]
  3. Estimate efficacy of seviteronel as measured by progression-free survival (PFS) [ Time Frame: At least monthly over the first eight 28-day cycles ]
  4. Describe the safety profile of seviteronel [ Time Frame: Duration of the study ]
  5. Compare the safety profile of seviteronel with or without concurrent glucocorticoid administration [ Time Frame: Duration of the study ]
  6. Compare the CBR16 with or without concurrent glucocorticoid administration for female subjects with TNBC [ Time Frame: Duration of the study ]


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

Inclusion Criteria

Each subject eligible to participate in this study must meet or have all the following criteria:

  1. Is 18 years of age or older.
  2. Can provide written informed consent or have their legal representatives provide written informed consent
  3. Have documented histological or cytological evidence of invasive cancer of the breast, defined by one of the following:

    • ER+ breast cancer, defined as positive if ≥ 1% by IHC and HER2 normal, defined as IHC 0-1+ or IHC 2+(and FISH<2), or FISH < 2.0
    • TNBC, defined as ER-/PgR- if 0 % by IHC and HER2 normal, defined as IHC 0-1+ or IHC 2+(and FISH<2), or FISH < 2.0
  4. ECOG PS of 0 or 1 for Females, 0, 1, or 2 for Males.
  5. Undergoing or willing to undergo gonadal suppression:

    • Female subjects with ER+/HER2 normal tumors must be post-menopausal defined by local practice. Ovarian suppression with a LHRH analogue to achieve cessation of regular menses is allowed on study
    • Male subjects must be undergoing or willing to undergo gonadal suppression whilst on study drug and continue with the LHRH analogue for the duration of the study
  6. Subjects must have adequate hematopoietic function as evidenced by:

    • WBC ≥ 3,000/μl
    • ANC ≥ 1,500/μl
    • Platelet count ≥ 100,000/μl
    • HGB ≥ 9 g/dl and not transfusion dependent
  7. Adequate liver function, including all the following:

    • Total serum bilirubin ≤2.0 x ULN unless the subject has documented Gilbert syndrome;
    • Aspartate and alanine aminotransferase (AST & ALT) ≤3.0 x ULN or ≤5.0 x ULN if subject has liver metastasis;
    • Alkaline phosphatase ≤3.0 x ULN or ≤5 x ULN in case of bone metastasis and/or hepatic metastasis
  8. Subjects must have adequate renal function as evidenced by a serum creatinine of ≤ 2.0 mg/dl.
  9. Potassium (K+) ≥3.5 mEq/L
  10. Women of child-bearing potential must have a negative serum or urine pregnancy test within 72 hours of C1D1.
  11. Women of child-bearing potential and male subjects with a female partner of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at Screening and continuing throughout the study period and for 3 months after final study drug administration i. Two acceptable forms of birth control include:

1. Condom (barrier method of contraception), and 2. One of the following:

  1. Oral, injected or implanted hormonal contraception
  2. Placement of an intrauterine device (IUD) or intrauterine system (ISU)
  3. Additional barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
  4. Vasectomy or surgical castration ≥ 6 months prior to Screening. 12. Able to swallow study medication 13. Able to comply with study requirements

Exclusion Criteria

  1. Received any investigational agent within 5 half-lives of the agent in question; if the half-life is not known, ≤ 28 days of C1D1.
  2. Received palliative radiotherapy ≤ 2 weeks of C1D1
  3. Received any other therapeutic treatment for breast cancer ≤ 2 weeks of C1D1, except for hormonal therapies.
  4. Symptomatic CNS metastases.
  5. History of another invasive malignancy ≤ 3 years of C1D1.
  6. A QTcF interval >470 msec on the Screening ECG. If the ECG QTcF interval is >470 msec, then the mean QTcF of a triplicate ECGs can be used and if the mean is <470 msec, the subject may be enrolled.
  7. 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).
  8. Class III or IV Congestive Heart Failure (CHF) as defined by the New York Heart Association (NYHA) functional classification system within the previous 6 months
  9. Initiated a bone modifying agent (e.g. denosumab) ≤ 28 days of C1D1.
  10. Any medical condition that could preclude their participation in the study, pose an undue medical hazard, or which could interfere with the interpretation of the study results.
  11. A history of seizure ≤ 2 years of C1D1 or those who require prophylactic anti-seizure medications.
  12. A history of loss of consciousness or transient ischemic attack ≤ 12 months before C1D1.
  13. Known active HIV, Hepatitis B, or Hepatitis C infections.
  14. Known or suspected hypersensitivity to seviteronel, or any components of the formulation.
  15. Any other condition which in the opinion of the investigator would preclude participation in the study.

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): NCT02580448


  Show 36 Study Locations
Sponsors and Collaborators
Innocrin Pharmaceutical
Investigators
Study Chair: Victoria Brown, BS Sponsor GmbH

Responsible Party: Innocrin Pharmaceutical
ClinicalTrials.gov Identifier: NCT02580448     History of Changes
Other Study ID Numbers: INO-VT-464-CL-006
First Posted: October 20, 2015    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018

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