Once-daily Oral Seviteronel in Patients With Castration-Resistant Prostate Cancer Progressing on Enzalutamide or Abiraterone.

Prostate Cancer Clinical Trial

Official title:

A Phase 2 Open-label Study to Evaluate the Efficacy and Safety of Seviteronel in Subjects With Castration-Resistant Prostate Cancer Progressing on Enzalutamide or Abiraterone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02445976
• Other study ID #: INO-VT-464-CL-003
• Secondary ID: VMT-VT-464-CL-00
• Status: Completed
• Phase: Phase 2
• Start date: May 2015
• Est. completion date: January 2019

Study information

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

Clinical Trial Summary

The goal of this clinical study is to determine the efficacy and safety of Seviteronel, a lyase-selective inhibitor of CYP17 and an androgen receptor antagonist, in patients with castration-resistant prostate cancer (CRPC) who have been previously treated with enzalutamide and/or abiraterone.

Description:

This is a phase 2 clinical trial of Seviteronel (an oral, potent and lyase-selective CYP17 inhibitor) in men with castration-resistant prostate cancer (CRPC) progressing on enzalutamide or abiraterone. Approximately 197 subjects will be used to assess treatment efficacy. The study will be conducted in two different clinical cohorts separated by prior exposure to enzalutamide or abiraterone, or prior exposure to enzalutamide and abiraterone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 197
• Est. completion date: January 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

1. Subjects must be =18 years of age.

2. Subjects or their legal representatives must be able to provide written informed consent.

3. Subjects must have documented histological or cytological evidence of adenocarcinoma of the prostate.

4. Subjects must have an ECOG Performance Score of 0-1.

5. Subjects must have undergone orchiectomy, or have ongoing LHRH analogue therapy prior to drug initiation. Subjects on LHRH analogues must remain on these agents for the duration of the study.

6. Subjects must have castrate levels of testosterone (=50 ng/dl [1.7 nmol/L]) and have progressive disease at Screening defined as PSA rise determined by a minimum of 2 rising PSA values =1 week between each assessment. The PSA value at the Screening visit must be =2ng/mL with or without:

• Soft tissue disease progression defined by RECIST 1.1 at Screening or = 28 days of C1D1. Measurable disease is not required for entry. Lymph nodes = 1.5cm (short axis) are considered measurable disease (PCWG3)

• Bone disease progression defined by =2 new lesions on bone scan at Screening, or =28 days of C1D1

7. Subjects must have received abiraterone and/or enzalutamide. Subject must have received either abiraterone or enzalutamide for =12 weeks. Other second generation CYP17 inhibitors/androgen receptor antagonists including but not limited to TAK-700 (orteronel), TOK-001 (galeterone) may have been taken in place of abiraterone and ARN-509 (apalutamide) may have been taken in place of enzalutamide.

8. Subjects 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. Subjects must have adequate liver function, including all of 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 =2.0 x ULN or =5 x ULN in case of bone metastasis and/or hepatic metastasis

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

11. Subjects must have potassium (K+) >3.5 mEq/l.

12. Subject and his female partner who is 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 a Screening and continuing throughout the study period and for 3 months after final study drug administration • 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. 13. Subjects able to swallow study medication 14. Subjects able to comply with study requirements

Exclusion Criteria

1. Subjects who have completed sipuleucel-T (Provenge ®) treatment within 28 days of study drug initiation.

2. Subjects on 5-alpha reductase inhibitors such as finasteride (PROSCAR®, PROPECIA®), or dutasteride (AVODART®) within 28 days of study drug initiation.

3. Subjects who received any investigational agent =28 days of study drug initiation.

4. Subjects who received palliative radiotherapy =2 weeks of study drug initiation.

5. Subjects with symptomatic CNS metastases.

6. Subjects with a history of another invasive malignancy =3 years of study drug initiation.

7. Subjects with a QTcF interval of >470 msec; if the Screening ECG QTcF interval is >470 msec, it may be repeated, and if repeat <470 msec, the subject may be enrolled.

8. Subject with clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second degree or third degree atrioventricular heart block without a permanent pacemaker in place)

9. Subject that started a bone modifying agent (e.g. bisphosphonates, denosumab) = 28 days of study drug initiation (note: ongoing bone modifying agents administered > 28 days are allowed).

10. Subject with any medical condition that could preclude subject participation in the study, pose an undue medical hazard, or which could interfere with study results.

11. Subject with Class III or IV Congestive Heart Failure as defined by the New York Heart Association (NYHA) functional classification system within the previous 6 months.

12. Subject with a history of loss of consciousness or transient ischemic attack = 12 months of study drug initiation.

13. Subject with known active HIV, Hepatitis B, or Hepatitis C infections.

14. Subject with known or suspected hypersensitivity to seviteronel, or any components of the formulation

15. Subject with any other condition which in the opinion of the investigator would preclude participation in the study.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Seviteronel: given orally once daily in 28-day cycles
Oral Seviteronel given once daily, in continuous 28-day cycles at the recommended Phase 2 dose

Locations

Country	Name	City	State
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	University of Alabama	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Virginia Oncology Associates	Hampton	Virginia
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	University of California at Los Angeles	Los Angeles	California
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Yale University	New Haven	Connecticut
United States	Tulane University	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	GU Research Network	Omaha	Nebraska
United States	Washington University	Saint Louis	Missouri
United States	Mayo Clinic	Scottsdale	Arizona
United States	University of Washington	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (3)

Lead Sponsor	Collaborator
Innocrin Pharmaceutical	Prostate Cancer Clinical Trials Consortium, Prostate Cancer Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients who have a PSA response by while on study from starting treatment with seviteronel	PSA response at any time whilst on study from the start of treatment within seviteronel defined by a = 50% decrease in serum PSA.	6 months
Primary	The time to radiographic disease progression by RECIST 1.1 or PCWG3	Median time to radiographic disease progression evaluated by computerized tomography (CT scan) or magnetic resonance imaging (MRI) and radionuclide bone scans by RECIST 1.1 or Prostate Cancer Clinical Trials Working Group 3 (PCWG3)	10 months