Safety and Anti-Tumor Study of Oral EPI-506 for Patients With Metastatic Castration-Resistant Prostate Cancer

• Sponsor: ESSA Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02606123
• Collaborator: (none)
• Enrollment: 28
• Locations: 5
• Arm: 1
• Duration (Months): 26
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The study will consist of 2 parts: Part I (Dose Escalation) and Part II (Dose Expansion). In Part I, patients will participate in single, multiple, and long-term dosing periods using EPI-506 to determine safety, pharmacokinetics, the maximum tolerated dose, and preliminary indications of anti-tumor activity. Part I is an open-label, adaptive 3 + 3 design, dose-escalation study. Approximately six dose levels of EPI-506 will be studied, beginning at 80 mg/day. Enrolled patients may be allowed to escalate to a subsequent dose cohort after their initial twelve weeks. Additional patients may be enrolled at any safe dose level prior to or concurrent with enrolling patients in Part II.

In Part II, 3 patient populations; post-abiraterone metastatic castration-resistant prostate cancer (mCRPC) but enzalutamide-naïve, post-enzalutamide mCRPC but abiraterone-naïve, and post-abiraterone and enzalutamide mCRPC will be studied at the recommended Phase 2 dose (RP2D) determined in Part I over 12 weeks of daily dosing. Approximately 120 patients (40 in each cohort) will be enrolled.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases	Drug: EPI-506	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Open-Label Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral EPI-506 in Patients With Metastatic Castration-Resistant Prostate Cancer
• Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: EPI-506 Part I: Ascending doses of EPI-506 administered orally to define the maximum tolerated dose.

Drug: EPI-506; Patients will receive EPI-506 as an oral softgel capsule. Part 1: Approximately six dose levels of EPI-506 will be studied, beginning at 80 mg/day. During the Single-Dose Period, patients will first receive a dose of EPI-506 in the fasted state followed by 2 days of washout, and then patients will receive a second dose of EPI-506 in the fed state followed by 2 days of washout. Patients will then enter the Multiple Dosing and Long-term Dosing Period where they will receive once or twice daily dosing in a fed or fasted state until they meet discontinuation criteria. Part 2: The dose in Part 2 will be determined in Part 1 of the study. Patients will receive the Part 2 dose daily until they meet discontinuation criteria.

Outcome Measures

Primary Outcome Measures

1. Part I: Safety and tolerability assessed by vital signs, laboratory measurements, and frequency and severity of treatment-related adverse events [12 weeks]

2. Part II: Prostate-specific antigen (PSA) response rate [12 weeks]

Secondary Outcome Measures

1. Part I: Define the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) [9 months]

2. Part I: Pharmacokinetics (PK) profile of EPI-506 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

   Assessed by plasma area under the plasma concentration-time curve (AUC)

3. Part I: Pharmacokinetics (PK) profile of EPI-506 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

   Assessed by maximum concentration (Cmax)

4. Part I: Pharmacokinetics (PK) profile of EPI-506 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

   Assessed by observed pre-dose plasma concentration during multiple dosing (Ctrough)

5. Part I: Pharmacokinetics (PK) profile of EPI-506 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

   Assessed by time to reach Cmax (tmax)

6. Part I: Pharmacokinetics (PK) profile of EPI-506 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

   Assessed by apparent terminal elimination half-life (t1/2)

7. Part I: Pharmacokinetics (PK) profile of EPI-506 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

   Assessed by apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)

8. Part I: Pharmacokinetics (PK) profile of EPI-506 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

   Assessed by apparent clearance after extravascular administration (CL/F)

9. Part I: Pharmacokinetics (PK) profile of EPI-002 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

   Assessed by AUC

10. Part I: Pharmacokinetics (PK) profile of EPI-002 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

    Assessed by Cmax

11. Part I: Pharmacokinetics (PK) profile of EPI-002 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

    Assessed by Ctrough

12. Part I: Pharmacokinetics (PK) profile of EPI-002 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

    Assessed by tmax

13. Part I: Pharmacokinetics (PK) profile of EPI-002 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

    Assessed by t1/2

14. Part I: Pharmacokinetics (PK) profile of EPI-002 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

    Assessed by Vz/F

15. Part I: Pharmacokinetics (PK) profile of EPI-002 [Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.]

    Assessed by CL/F

16. Part I: Food effect on PK [6 days]

    Following a single-dose of EPI-506 on Days 1 and 4 assessed by AUC

17. Part I: Food effect on PK [6 days]

    Following a single-dose of EPI-506 on Days 1 and 4 assessed by Cmax

18. Part I: Food effect on PK [6 days]

    Following a single-dose of EPI-506 on Days 1 and 4 assessed by Ctrough

19. Part I: Food effect on PK [6 days]

    Following a single-dose of EPI-506 on Days 1 and 4 assessed by tmax

20. Part I: Food effect on PK [6 days]

    Following a single-dose of EPI-506 on Days 1 and 4 assessed by t1/2

21. Part I: Food effect on PK [6 days]

    Following a single-dose of EPI-506 on Days 1 and 4 assessed by Vz/F

22. Part I: Food effect on PK [6 days]

    Following a single-dose of EPI-506 on Days 1 and 4 assessed by CL/F

23. Part I: PSA [Baseline to Week 12]

    Evaluated as a Pharmacodynamic (PD) marker of response

24. Part II: Safety and tolerability assessed by vital signs, laboratory measurements, and frequency and severity of treatment-related adverse events [12 months]

25. Part II: To evaluate the PK of EPI-506 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by AUC

26. Part II: To evaluate the PK of EPI-506 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by Cmax

27. Part II: To evaluate the PK of EPI-506 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by Ctrough

28. Part II: To evaluate the PK of EPI-506 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by tmax

29. Part II: To evaluate the PK of EPI-506 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by t1/2

30. Part II: To evaluate the PK of EPI-506 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by Vz/F

31. Part II: To evaluate the PK of EPI-506 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by CL/F

32. Part II: To evaluate the PK of EPI-002 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by AUC

33. Part II: To evaluate the PK of EPI-002 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by Cmax

34. Part II: To evaluate the PK of EPI-002 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by Ctrough

35. Part II: To evaluate the PK of EPI-002 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by tmax

36. Part II: To evaluate the PK of EPI-002 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by t1/2

37. Part II: To evaluate the PK of EPI-002 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by Vz/F

38. Part II: To evaluate the PK of EPI-002 [Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.]

    Assessed by CL/F

39. Part II: Time to PSA progression [12 months]

40. Part II: Radiographic progression [12 weeks]

    Radiographic progression evaluated per modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1

41. Part II: Objective response [12 weeks]

    Radiographic progression evaluation per mRECIST v1.1 in patients with measurable soft tissue disease at baseline

Other Outcome Measures

1. Exploratory Objective: Biomarkers [12-24 months]

   Circulating tumor cells (CTCs) with emphasis on androgen receptor splice variants (AR-V7)

2. Exploratory Objective: Pain assessments [12-24 months]

   Assessed by Brief Pain Inventory-Short Form (BPI-SF) instrument

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Adenocarcinoma of the Prostate

• Metastatic Disease with at least one lesion on bone scan and/or soft tissue on CT/MRI

• Demonstrated progression on abiraterone and/or enzalutamide

• Demonstrated PSA progression within 12 weeks of study participation

• Castrate testosterone levels at screening with continued Luteinizing hormone-releasing hormone (LHRH) therapy

• Eastern Cooperative Oncology Group (ECOG) score between 0-1

• Asymptomatic or mildly symptomatic

Exclusion Criteria:

• Candidates for cytotoxic chemotherapy

• Received more than one line of chemotherapy

• Received more than one treatment course of enzalutamide or abiraterone

• Inadequate washout of prohibited hormonally active agents or other prior treatments for prostate cancer (PCa)

• Known intra-cerebral disease or brain mets

• Spinal cord compression within 6 months

• Prior treatment with investigative androgen receptor (AR) agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Scottsdale Healthcare Hospitals DBA HonorHealth	Scottsdale	Arizona	United States	85258
2	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
3	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
4	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
5	British Columbia Cancer Agency - Vancouver Centre	Vancouver	British Columbia	Canada	V5Z 4E6

Sponsors and Collaborators

• ESSA Pharmaceuticals

Investigators

• Study Director: Frank Perabo, MD, PhD, ESSA Pharmaceuticals Corp.
• Principal Investigator: Robert B. Montgomery, MD, Seattle Cancer Care Alliance
• Principal Investigator: Kim N. Chi, MD, British Columbia Cancer Agency - Vancouver Centre

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ESSA Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02606123
• Other Study ID Numbers: EPI-506-CS-0001
• First Posted: Nov 17, 2015
• Last Update Posted: Mar 1, 2018
• Last Verified: Feb 1, 2018

• Keywords provided by ESSA Pharmaceuticals: Prostate Cancer; Metastatic castration-resistant prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Neoplasms; Genital Neoplasms, Male; Prostatic Diseases

Study Results

No Results Posted as of Mar 1, 2018