To Evaluate Safety and Tolerability of VERU-111 in Men With Advanced Metastatic Castration Resistant Prostate Cancer

NCT03752099 | Terminated Phase 1 FDA Drug

• 1 other identifier: V1011101
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 13

Brief Summary

Phase 1b - To assess the safety/tolerability of VERU-111 and to determine the maximum tolerated dose of VERU-111 in patients with metastatic, castration resistant prostate cancer who have failed a novel androgen blocking agent therapy (mCRPC). Phase 2 - To estimate the PSA50 response rate, defined as a decline in PSA to ≥50% of baseline level, confirmed with a second measurement at least 3 weeks apart (PCWG3).

Conditions

Metastatic Castration Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose

  Patients will be assessed for toxicities at each clinical evaluation. Toxicities will be graded according to CTCAE v5.0 standardized grading scales. The incidence of grade 3-5 toxicities will be reported.Toxicities will be reported as a tabulated table by type and grade.

  21 Days

• PSA50 Response Rate

  Decrease in the PSA to ≥50% less than the baseline PSA upon enrollment in the trial. The decrease must be confirmed by a second measurement at least 3 weeks apart. PSA values will be measured monthly during the trial. All patients who take at least one dose of VERU-111 will be considered evaluable for the primary endpoint. If patients do not have at least one follow-up PSA after initiation of VERU-111 due to stopping therapy for toxicity or withdrawing consent, then they will be replaced. PSA50 response rate will be estimated along with 95% confidence interval.

  63 Days

Secondary Outcomes (4)

• PSA progression-free survival

  63 Days

• Progression-free survival

  63 days

• Percentage of Patients who achieve Objective Response Rate

  63 Days

• Number of participants with treatment related adverse events (Safety and Tolerability)

  91 Days

Study Arms (6)

VERU-111 4.5mg

EXPERIMENTAL

Daily dosing on Day 1-7 of each 21-day cycle for 3 cycles Treatment may continue past the planned three 21-day cycles until DLT or disease progression is observed.

Drug: VERU-111

VERU-111 9mg

EXPERIMENTAL

Daily dosing on Day 1-7 of each 21-day cycle for 3 cycles Treatment may continue past the planned three 21-day cycles until DLT or disease progression is observed.

Drug: VERU-111

VERU-111 18mg

EXPERIMENTAL

Daily dosing on Day 1-7 of each 21-day cycle for 3 cycles Treatment may continue past the planned three 21-day cycles until DLT or disease progression is observed.

Drug: VERU-111

VERU-111 27mg

EXPERIMENTAL

Daily dosing on Day 1-7 of each 21-day cycle for 3 cycles Treatment may continue past the planned three 21-day cycles until DLT or disease progression is observed.

Drug: VERU-111

VERU-111 36mg

EXPERIMENTAL

Daily dosing on Day 1-7 of each 21-day cycle for 3 cycles Treatment may continue past the planned three 21-day cycles until DLT or disease progression is observed.

Drug: VERU-111

VERU-111 45mg

EXPERIMENTAL

Daily dosing on Day 1-7 of each 21-day cycle for 3 cycles Treatment may continue past the planned three 21-day cycles until DLT or disease progression is observed.

Drug: VERU-111

Interventions

VERU-111 DRUG

VERU-111

Also known as: Bisindole

VERU-111 18mg; VERU-111 27mg; VERU-111 36mg; VERU-111 4.5mg; VERU-111 45mg; VERU-111 9mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be included in this study, patients should meet all of the following criteria:
• Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.
• NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
• Patients \>18 years of age.
• Histological or cytologic proof of adenocarcinoma of the prostate.
• Radiographic evidence of metastatic disease by CT scan or MRI and/or bone scan.
• Known castration resistant prostate cancer, defined according to PCWG3 criteria.
• Subjects who have metastatic castration resistant prostate cancer that have maintained ADT and have failed a novel androgen receptor agent (abiraterone or enzalutamide) defined as:
• Serum PSA progression of two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least two weeks apart.
• Documented bone lesions by the appearance of two or more new lesions on bone scintigraphy or dimensionally-measurable soft tissue metastatic lesion assessed by CT or MRI.
• Absolute PSA ≥2.0 ng/ml at screening.
• Prior chemotherapy for mCRPC:
• Phase 1b - ONE prior taxane chemotherapy for mCRPC will be allowed during the Phase 1b portion of study as long as the last dose was more than four weeks prior to the first dose of study drug.
• Phase 2 - Prior chemotherapy for mCRPC is not allowed in the Phase 2 portion of the study. Prior chemotherapy for metastatic hormone sensitive prostate cancer will not qualify as a prior chemotherapy and the last dose must be \>6 months prior to enrollment.
• Prior treatment with abiraterone, enzalutamide, bicalutamide, and/or ketoconazole is allowed. There is no limit on the maximum number or types of prior hormonal therapies received. The patients should be off prior therapy for at least two weeks (4 weeks off bicalutamide or nilutamide treatment) prior to first dose of study drug.

You may not qualify if:

• Patients that meet any of the criteria listed below will not be eligible for study entry:
• Histologic identification of small cell carcinoma of the prostate or neuroendocrine pathology in either biopsy or prostatectomy tissue.
• Has received external-beam radiotherapy within the last 2 weeks prior to start of study treatment.
• Patients receiving full dose anticoagulation therapy are not eligible for study.
• Patients with prior history of a thromboembolic event within the last 6 months.
• Participation in another clinical study with an investigational product during the last 4 weeks/28 days.
• Patients should be excluded if they have had prior systemic treatment with two prior taxane chemotherapies for advanced prostate cancer. No limit to other prior therapies.
• Concurrent use of other anticancer agents (see Appendix G) or treatments, with the following exceptions:
• o Ongoing treatment with denosumab (Prolia) or bisphosphonate (e.g., zoledronic acid) is allowed. Ongoing treatment should be kept at a stable schedule; however, if medically required, a change of dose, compound, or both is allowed.
• Any treatment modalities involving major surgery within 4 weeks prior to the start of study treatment.
• Patients are excluded if they have active known brain metastases or leptomeningeal metastases.
• Patients should be excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
• History of severe hypersensitivity reaction to any taxane chemotherapy.
• Has imminent or established spinal cord compression based on clinical findings and/or MRI.
• Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous.

Sponsors & Collaborators

• Veru Inc.: lead

Study Sites (13)

Colorado Urology

Golden, Colorado, 80401, United States

Location

Universal Axon

Miami, Florida, 33166, United States

Location

First Urology

Jeffersonville, Indiana, 47130, United States

Location

Regional Urology

Shreveport, Louisiana, 71106, United States

Location

Sidney Kimmel Comprehensive Cancer Center at John Hopkins

Baltimore, Maryland, 21231, United States

Location

Chesapeake Urology

Towson, Maryland, 21204, United States

Location

Associated Medical Professionals of NY, PLLC

Syracuse, New York, 13210, United States

Location

Sargon Research

Canton, Ohio, 44718, United States

Location

Urologic Consultants

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Urology Clinics of North Texas

Dallas, Texas, 75231, United States

Location

Research Network America

Houston, Texas, 77074, United States

Location

Urology San Antonio

San Antonio, Texas, 78229, United States

Location

Urology of Virginia

Virginia Beach, Virginia, 23462, United States

Location

MeSH Terms

Interventions

sabizabulin

Study Officials

• Barnette

  Veru Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: November 23, 2018
• Study Start: January 18, 2019
• Primary Completion: March 15, 2023
• Study Completion: March 15, 2023
• Last Updated: September 26, 2023

Record last verified: 2023-09

Locations

US (13)