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

• Sponsor: Innocrin Pharmaceutical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02580448
• Collaborator: (none)
• Enrollment: 175
• Locations: 36
• Arms: 3
• Actual Duration (Months): 41
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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 Design

• Study Type: Interventional
• Anticipated 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: Aug 1, 2015
• Actual Primary Completion Date: Jan 1, 2019
• Actual Study Completion Date: Jan 1, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Estimate efficacy of seviteronel as measured by clinical benefit rate at 16 weeks (CBR16) for female subjects with TNBC. [Duration of Study]

2. Estimate efficacy of seviteronel as measured by clinical benefit rate at 24 weeks (CBR24) for female subjects with ER+ BC. [Duration of Study]

3. Estimate efficacy of seviteronel as measured by CBR16 for all male BC subjects. [Duration of Study]

Secondary Outcome Measures

1. Describe the pharmacokinetics of seviteronel [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 [At least monthly over the first eight 28-day cycles]

3. Estimate efficacy of seviteronel as measured by progression-free survival (PFS) [At least monthly over the first eight 28-day cycles]

4. Describe the safety profile of seviteronel [Duration of the study]

5. Compare the safety profile of seviteronel with or without concurrent glucocorticoid administration [Duration of the study]

6. Compare the CBR16 with or without concurrent glucocorticoid administration for female subjects with TNBC [Duration of the study]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. ECOG PS of 0 or 1 for Females, 0, 1, or 2 for Males.

2. 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

1. 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

1. 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

1. Subjects must have adequate renal function as evidenced by a serum creatinine of ≤ 2.0 mg/dl.

2. Potassium (K+) ≥3.5 mEq/L

3. Women of child-bearing potential must have a negative serum or urine pregnancy test within 72 hours of C1D1.

4. 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:

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

6. Oral, injected or implanted hormonal contraception

7. Placement of an intrauterine device (IUD) or intrauterine system (ISU)

8. Additional barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

9. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wallace Tumor Institute- University of Alabama	Birmingham	Alabama	United States	35249
2	Clearview Cancer Institute	Huntsville	Alabama	United States	35805
3	University of Colorado	Aurora	Colorado	United States	80045
4	Rocky Mountain Cancer Centers	Lakewood	Colorado	United States	80228
5	Florida Cancer Specialists	Fort Myers	Florida	United States	33916
6	Florida Cancer Specialists- North	Saint Petersburg	Florida	United States	33705
7	Georgia Cancer Center at Augusta University	Augusta	Georgia	United States	30912
8	SCRI - HCA Midwest Division	Kansas City	Kansas	United States	61432
9	University of Louisville Hospital / James Brown Cancer Center	Louisville	Kentucky	United States	40202
10	Maryland Oncology Hematology	Silver Spring	Maryland	United States	20902
11	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
12	University of Michigan	Ann Arbor	Michigan	United States	48109
13	Henry Ford Hospital	Detroit	Michigan	United States	48202
14	Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
15	Cancer Network/Oncology Associates PC	Omaha	Nebraska	United States	68118
16	Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
17	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
18	North Shore Hematology Oncology Associates	East Setauket	New York	United States	11733
19	Memorial Sloan Kettering	New York	New York	United States	10065
20	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
21	Novant Health Presbyterian Medical Center - Oncology Research	Charlotte	North Carolina	United States	28204
22	Duke University	Durham	North Carolina	United States	27710
23	Gabrail Cancer Center Research	Canton	Ohio	United States	44718
24	Oncology Hematology Care, Inc	Cincinnati	Ohio	United States	45242
25	The Ohio State University	Columbus	Ohio	United States	43202
26	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
27	OHSU Knight Cancer Institute	Portland	Oregon	United States	97239
28	Charleston Hematology and Oncology Associates	Charleston	South Carolina	United States	29414
29	Precision Cancer Research/Brig Center for Cancer Care and Survivorship, LLC	Knoxville	Tennessee	United States	37909
30	SCRI Tenessee Oncology Nashville	Nashville	Tennessee	United States	37203
31	Mary Crowley Cancer Research Centers	Dallas	Texas	United States	75230
32	The University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
33	The Center for Cancer and Blood Disorders (Fort Worth)	Fort Worth	Texas	United States	76104
34	US Oncology	Fort Worth	Texas	United States	76177
35	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
36	Virginia Oncology Associates	Norfolk	Virginia	United States	23502

Sponsors and Collaborators

• Innocrin Pharmaceutical

Investigators

• Study Chair: Victoria Brown, BS, Sponsor GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Innocrin Pharmaceutical
• ClinicalTrials.gov Identifier: NCT02580448
• Other Study ID Numbers: INO-VT-464-CL-006
• First Posted: Oct 20, 2015
• Last Update Posted: Feb 1, 2019
• Last Verified: Jan 1, 2019

• 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; Seviteronel

Study Results

No Results Posted as of Feb 1, 2019