Phase II Study of PARP Inhibitor Olaparib and IV Ascorbate in Castration Resistant Prostate Cancer

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins2 sites in 1 country4 target enrollmentJune 30, 2023

ConditionsProstate Cancer Castration-resistant Prostate Cancer

InterventionsOlaparib Vitamin C

DrugsOlaparib

Overview

Phase: Phase 2
Intervention: Olaparib
Conditions: Prostate Cancer
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Enrollment: 4
Locations: 2
Primary Endpoint: PSA50 Response
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a study to evaluate the safety and clinical activity of the combination of olaparib and high-dose IV ascorbate, as second or later line of therapy, in castration resistant prostate cancer patients with no known DNA repair gene mutations (DDRm). In brief, the primary endpoint is PSA50 response , defined by a 50% reduction in PSA from baseline . The secondary endpoints are assessing the PSA doubling time, radiographic and PSA PFS, safety and tolerability as defined by the incidence of grade 3 to 5 toxicities, and measuring overall survival.

Registry

clinicaltrials.gov

Start Date

June 30, 2023

End Date

October 14, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

Male

Investigators

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Have metastatic castration-resistant prostate cancer (prostate cancer progressing by PSA (rise by 25% on prior therapy) or imaging despite castrate levels of testosterone \[\<50 ng/dL\] using standard measures of progression defined by Prostate Cancer Working Group3)
•Have a minimum PSA of 1 ng/mL
•Have a pathological diagnosis of prostate carcinoma
•Patients should continue receiving continuous hormonal ablation with surgical or medical castration with baseline testosterone \<50ng/dL
•Patients may be receiving bone-targeted agents
•May have received multiple lines of therapy including radium 223, sipuleucel T, and up to 2 lines of chemotherapy (One of 2 lines may be for hormone sensitive metastatic prostate cancer or both can be for castration resistant).
•Age \>= 18
•Have ECOG performance status 0-1 (Appendix A)
•Be able to take oral medication and willing to consider a port for ease of administration of ascorbate
•Must have progressed on one systemic line of treatment (can include LHRH agonist/antagonist or orchiectomy and one additional line of therapy (abiraterone, enzalutamide, apalutamide, darolutamide, docetaxel, etc))

Exclusion Criteria

•Have a known DNA repair mutation (minimum list of genes that must be mutation negative for inclusion: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD45L). In addition, patients who have not completed germline and somatic testing to rule out such a mutation are ineligible until they have completed testing. If tissue or liquid ctDNA sequencing was not previously done, testing using the Foundation One liquid biopsy test or an equivalent FDA-approved test is acceptable as standard of care.
•DNA repair mutation variant of unknown significance (VUS) allowed
•Have had known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
•Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
•No prior olaparib, rucaparib, or other PARP inhibitor
•Have had major surgery within 2 weeks of dosing of investigational agent
•Have had palliative radiation or another biological cancer therapy within 2 weeks prior to the first dose of study drug (2 week wash out required)
•Patients receiving any systemic chemotherapy or radiotherapy within 3 weeks prior to study treatment
•Have received other investigational drugs within 14 days prior to enrollment.
•Is expected to require chemotherapy or radiation for pain palliation in the next 12 weeks.

Arms & Interventions

Olaparib and Vitamin C

Olaparib will be administered at 300 mg by mouth, twice daily; ascorbate will be administered at 1 g/kg IV twice weekly at least 24 hours apart, until objective disease progression or unacceptable toxicities or patient withdrawal for other reasons.

Intervention: Olaparib

Olaparib and Vitamin C

Intervention: Vitamin C

Outcomes

Primary Outcomes

PSA50 Response

Time Frame: up to 5 years

Number of participants with metastatic castration resistance prostate cancer (mCRPC) who experience a 50% reduction in prostate specific antigen (PSA50) from baseline. PSA50 response will be defined as a 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 4 weeks apart. PSA values will be measured monthly during the trial.

Secondary Outcomes

Safety and Tolerability of Olaparib in Combination With IV Ascorbic Acid in Patients With mCRPC(up to 1 year 4 months)
PSA Progression Free Survival (PSA PFS) of Patients With mCRPC Receiving Olaparib in Combination With IV Ascorbic Acid(up to 5 years)
PSA Doubling Time in Patients With mCRPC Receiving Olaparib in Combination With IV Ascorbic Acid(up to 5 years)
Radiographic Progression Free Survival (rPFS) of Patients With mCRPC Receiving Olaparib in Combination With IV Ascorbic Acid(up to 5 years)
Overall Survival of Patients With mCRPC Receiving Olaparib in Combination With IV Ascorbic Acid(up to 5 years)