Addition of Opaganib to Androgen Antagonists in Patients With mCRPC

• ClinicalTrials.gov Identifier: NCT04207255
• Recruitment Status: Active, not recruiting
• First Posted: December 20, 2019
• Last Update Posted: March 7, 2023
• Sponsor: Medical University of South Carolina
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Medical University of South Carolina

Study Description

Brief Summary:

This is a Phase II study of the investigational drug opaganib. Patients with metastatic castration resistant prostate cancer (mCRPC) who have experienced disease progression while receiving abiraterone or enzalutamide will receive Opaganib at either 250 mg or 500 mg by mouth twice a day continuously. Patients will continue on study drug until the development of progressive disease, intolerable toxicity, withdrawal of patient consent or other event as outlined in patient discontinuation.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Opaganib; Drug: Abiraterone; Drug: Enzalutamide	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 67 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of the Addition of Opaganib to Androgen Antagonists in Patients With Prostate Cancer Progression on Enzalutamide or Abiraterone
• Actual Study Start Date: March 27, 2020
• Estimated Primary Completion Date: March 31, 2023
• Estimated Study Completion Date: June 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 2: Opaganib with abiraterone	Drug: Opaganib; 500mg of Opaganib orally twice a day continuously.; Drug: Abiraterone; IV as directed by SOC
Experimental: Cohort 3: Opaganib with enzalutamide	Drug: Opaganib; 500mg of Opaganib orally twice a day continuously.; Drug: Enzalutamide; IV as directed by SOC
Experimental: Cohort 1a: Opaganib with abiraterone	Drug: Abiraterone; IV as directed by SOC; Drug: Opaganib; 250mg of Opaganib orally twice a day continuously.
Experimental: Cohort 1b: Opaganib with enzalutamide	Drug: Enzalutamide; IV as directed by SOC; Drug: Opaganib; 250mg of Opaganib orally twice a day continuously.

Outcome Measures

Primary Outcome Measures :

1. Disease control status [ Time Frame: 113 days ]
   Stable disease or better according to Prostate Cancer Working Group 3 (PCWG3) criteria after four cycles of treatment

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient must have mCRPC. Each patient must have:

   • Tissue diagnosis documented by pathology report, or clinic note attesting to same.
   • Radiographically-demonstrated metastases
   • Patients must have adenocarcinoma, or ductal carcinoma, or combinations of these two entities
2. Voluntary, signed and dated, institutional review board (IRB)-approved informed consent form in accordance with regulatory and institutional guidelines.
3. Documented progression during treatment with enzalutamide or abiraterone, as determined by the enrolling investigator.
4. Testosterone level documented to be less than 50ng/
5. 18 years of age or older.
6. ECOG performance status of 0-2.

7. Acceptable liver function:

   • Bilirubin ≤ 1.5 times upper limit of normal (CTCAE Grade 1 baseline)
   • AST (SGOT) & ALT (SGPT) ≤ 3 x ULN (CTCAE Grade 1 baseline)
   • Subjects with Gilbert's syndrome may be included if the total bilirubin is <3x ULN and the direct bilirubin is within normal limits
8. Acceptable kidney function indicated by serum creatinine ≤ 1.5 X ULN (CTCAE Grade 1 baseline)

9. Acceptable hematologic status:

   • Absolute neutrophil count ≥ 1000 cells/mm3,
   • Platelet count ≥ 75,000 (plt/mm3) (CTCAE Grade 1 baseline)
   • Hemoglobin ≥ 9.0 g/dL.
10. Fasting blood glucose of <165mg/dL
11. Urinalysis: no clinically significant abnormalities
12. International normalized ratio (INR) ≤1.7
13. Well-controlled blood pressure as determined by the treating investigator
14. Patients requiring narcotic analgesics must be on stable doses for at least 2 weeks prior to study entry.

Exclusion Criteria:

1. New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
2. Underlying psychiatric disorder requiring hospitalization within the last two years.
3. Clinically significant neurological disorder (Parkinson's disease, dementia, multiple sclerosis), as determined by the enrolling investigator.
4. Active, uncontrolled bacterial, viral or fungal infection, requiring systemic therapy.
5. Treatment with radiation therapy, surgery, or investigational therapy within 28 days prior to registration.
6. Unwillingness or inability to comply with procedures required in this protocol.
7. Serious nonmalignant disease that could compromise protocol objectives in the opinion of the Investigator.
8. Patients who are receiving coumadin, apixaban, argatroban or rivaroxaban. Patients who are receiving other drugs that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes that cannot be stopped at least 7 days or 5 half-lives (whichever is longer) before starting treatment with opaganib may be treated on this study with careful monitoring for toxic effects or loss of efficacy of the relevant drug. A list of commonly used drugs that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes with the half-life of each drug identified, is included as an Appendix C.
9. Patients who are currently participating in any other clinical trial of an investigational product.
10. Other primary malignancy requiring systemic treatment within past 5 years except carcinoma in situ of the cervix or urinary bladder or non-melanoma skin cancer.
11. Any other mental incapacitation or psychiatric illness that would preclude study participation, as determined by the enrolling investigator.
12. Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.

Contacts and Locations

Locations

United States, Georgia

Emory University

Atlanta, Georgia, United States, 20322

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Medical University of South Carolina

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Michael Lilly, MD; Medical University of South Carolina

  Study Documents (Full-Text)

Documents provided by Medical University of South Carolina:

Study Protocol and Statistical Analysis Plan  [PDF] June 8, 2021

Informed Consent Form  [PDF] July 2, 2021

More Information

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT04207255
• Other Study ID Numbers: Pro00095537; 1P01CA203628-01 ( U.S. NIH Grant/Contract ); 103193 ( Other Identifier: MUSC )
• First Posted: December 20, 2019
• Last Update Posted: March 7, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Medical University of South Carolina:

Yeliva; ABC294640; 103193

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases