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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02580448
Recruitment Status : Completed
First Posted : October 20, 2015
Last Update Posted : February 1, 2019
Sponsor:
Information provided by (Responsible Party):
Innocrin Pharmaceutical

Tracking Information
First Submitted Date  ICMJE October 7, 2015
First Posted Date  ICMJE October 20, 2015
Last Update Posted Date February 1, 2019
Actual Study Start Date  ICMJE August 2015
Actual Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2018)
  • Estimate efficacy of seviteronel as measured by clinical benefit rate at 16 weeks (CBR16) for female subjects with TNBC. [ Time Frame: Duration of Study ]
  • 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 ]
  • Estimate efficacy of seviteronel as measured by CBR16 for all male BC subjects. [ Time Frame: Duration of Study ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 16, 2015)
  • Phase 1: Maximum tolerated dose of VT-464 in women with unresectable locally or advanced or metastatic breast cancer [ Time Frame: The first 28-day continuous dosing cycle at target dose ]
    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
  • Phase 2: CBRC16 for patients with androgen receptor (AR) positive TNBC (cohort 1) in their respective evaluable populations [ Time Frame: The first 28-day continuous dosing cycle at target dose ]
    To determine the clinical benefit rate (CBR) in patients with measurable disease. CBR consists of complete response , partial response, and stable disease lasting greater than 16 weeks
  • Phase 2: CBR24 for patients with ER(+)BC (cohort 2) in their respective evaluable populations [ Time Frame: The first 28-day continuous dosing cycle at target dose ]
    To determine the clinical benefit rate (CBR) in patients with measurable disease. CBR consists of complete response , partial response, and stable disease lasting greater than 24 weeks
Change History Complete list of historical versions of study NCT02580448 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2018)
  • 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
  • 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 ]
  • Estimate efficacy of seviteronel as measured by progression-free survival (PFS) [ Time Frame: At least monthly over the first eight 28-day cycles ]
  • Describe the safety profile of seviteronel [ Time Frame: Duration of the study ]
  • Compare the safety profile of seviteronel with or without concurrent glucocorticoid administration [ Time Frame: Duration of the study ]
  • Compare the CBR16 with or without concurrent glucocorticoid administration for female subjects with TNBC [ Time Frame: Duration of the study ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2015)
  • 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
  • Pharmacokinetics of VT-464 in the ITT population [ Time Frame: At least monthly over the first eight 28-day cycles ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CYP17 Lyase and Androgen Receptor Inhibitor Treatment With Seviteronel Trial (INO-VT-464-006; NCT02580448)
Official Title  ICMJE A Phase 1/2 Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Seviteronel in Subjects With Advanced Breast Cancer
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cancer of the Breast
  • Breast Cancer
  • Advanced Breast Cancer
  • Metastatic Breast Cancer
  • Male Breast Cancer
  • Triple Negative Breast Cancer
  • ER+ Breast Cancer
Intervention  ICMJE Drug: Seviteronel
Seviteronel given daily with evening meal in 28 day cycles
Study Arms  ICMJE
  • Experimental: Female Triple Negative Breast Cancer Patients
    TNBC Patients - Enrollment is complete in this cohort
    Intervention: Drug: Seviteronel
  • Experimental: Female Estrogen Receptor (+) Breast Cancer Patients
    Female ER(+) BC Patients - Enrollment is complete in this cohort
    Intervention: Drug: Seviteronel
  • Experimental: Male Breast Cancer Patients
    Locally advanced or metastatic males with BC
    Intervention: Drug: Seviteronel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: April 25, 2017)
175
Original Estimated Enrollment  ICMJE
 (submitted: October 16, 2015)
81
Actual Study Completion Date  ICMJE January 2019
Actual Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02580448
Other Study ID Numbers  ICMJE INO-VT-464-CL-006
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Innocrin Pharmaceutical
Study Sponsor  ICMJE Innocrin Pharmaceutical
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Victoria Brown, BS Sponsor GmbH
PRS Account Innocrin Pharmaceutical
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP