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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02580448
Other study ID # INO-VT-464-CL-006
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date August 2015
Est. completion date January 2019

Study information

Verified date January 2019
Source Innocrin Pharmaceutical
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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


Recruitment information / eligibility

Status Completed
Enrollment 175
Est. completion date January 2019
Est. primary completion date January 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Intervention

Drug:
Seviteronel
Seviteronel given daily with evening meal in 28 day cycles

Locations

Country Name City State
United States University of Michigan Ann Arbor Michigan
United States Georgia Cancer Center at Augusta University Augusta Georgia
United States University of Colorado Aurora Colorado
United States Wallace Tumor Institute- University of Alabama Birmingham Alabama
United States Massachusetts General Hospital Boston Massachusetts
United States Gabrail Cancer Center Research Canton Ohio
United States UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina
United States Charleston Hematology and Oncology Associates Charleston South Carolina
United States Novant Health Presbyterian Medical Center - Oncology Research Charlotte North Carolina
United States Oncology Hematology Care, Inc Cincinnati Ohio
United States The Ohio State University Columbus Ohio
United States Mary Crowley Cancer Research Centers Dallas Texas
United States The University of Texas Southwestern Medical Center Dallas Texas
United States Henry Ford Hospital Detroit Michigan
United States Duke University Durham North Carolina
United States North Shore Hematology Oncology Associates East Setauket New York
United States Florida Cancer Specialists Fort Myers Florida
United States The Center for Cancer and Blood Disorders (Fort Worth) Fort Worth Texas
United States US Oncology Fort Worth Texas
United States John Theurer Cancer Center at Hackensack University Medical Center Hackensack New Jersey
United States Clearview Cancer Institute Huntsville Alabama
United States SCRI - HCA Midwest Division Kansas City Kansas
United States Precision Cancer Research/Brig Center for Cancer Care and Survivorship, LLC Knoxville Tennessee
United States Rocky Mountain Cancer Centers Lakewood Colorado
United States University of Louisville Hospital / James Brown Cancer Center Louisville Kentucky
United States Masonic Cancer Center Minneapolis Minnesota
United States SCRI Tenessee Oncology Nashville Nashville Tennessee
United States Memorial Sloan Kettering New York New York
United States Virginia Oncology Associates Norfolk Virginia
United States Stephenson Cancer Center Oklahoma City Oklahoma
United States Cancer Network/Oncology Associates PC Omaha Nebraska
United States Nebraska Cancer Specialists Omaha Nebraska
United States OHSU Knight Cancer Institute Portland Oregon
United States Florida Cancer Specialists- North Saint Petersburg Florida
United States Huntsman Cancer Institute Salt Lake City Utah
United States Maryland Oncology Hematology Silver Spring Maryland

Sponsors (1)

Lead Sponsor Collaborator
Innocrin Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Estimate efficacy of seviteronel as measured by clinical benefit rate at 16 weeks (CBR16) for female subjects with TNBC. Duration of Study
Primary Estimate efficacy of seviteronel as measured by clinical benefit rate at 24 weeks (CBR24) for female subjects with ER+ BC. Duration of Study
Primary Estimate efficacy of seviteronel as measured by CBR16 for all male BC subjects. Duration of Study
Secondary Describe the pharmacokinetics of seviteronel Area under the curve concentration verses time curve and Peak Plasma Concentration At least monthly over the first eight 28-day cycles
Secondary Estimate efficacy of seviteronel as measured by the overall response rate (ORR) based on RECIST 1.1 At least monthly over the first eight 28-day cycles
Secondary Estimate efficacy of seviteronel as measured by progression-free survival (PFS) At least monthly over the first eight 28-day cycles
Secondary Describe the safety profile of seviteronel Duration of the study
Secondary Compare the safety profile of seviteronel with or without concurrent glucocorticoid administration Duration of the study
Secondary Compare the CBR16 with or without concurrent glucocorticoid administration for female subjects with TNBC Duration of the study
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