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

NCT05501548 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: J21127IRB00292465ESR 19-20448
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

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.

Conditions

Prostate Cancer; Castration-resistant Prostate Cancer

Keywords

olaparib; ascorbic acid; PARP; PARP-inhibitor

Outcome Measures

Primary Outcomes (1)

• PSA50 Response

  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.

  up to 5 years

Secondary Outcomes (5)

• Safety and Tolerability of Olaparib in Combination With IV Ascorbic Acid in Patients With mCRPC

  up to 1 year 4 months

• 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

• PSA Progression Free Survival (PSA PFS) 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

Study Arms (1)

Olaparib and Vitamin C

EXPERIMENTAL

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.

Drug: Olaparib; Dietary Supplement: Vitamin C

Interventions

Olaparib DRUG

Olaparib 300mg by mouth twice daily

Also known as: Lynparza, AZD2281, KU-0059436

Olaparib and Vitamin C

Vitamin C DIETARY_SUPPLEMENT

Ascorbic acid 1g/kg administered intravenously twice weekly

Also known as: Ascorbic acid, L-ascorbic acid, Ascor, A11GA01

Olaparib and Vitamin C

Eligibility Criteria

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

You may qualify if:

• 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))
• Have normal organ and marrow function measured within 28 days prior to administration of study treatment as defined below:
• Absolute neutrophil count \>1.5 x 109/L
• Platelets ≥ 100,000/mm³
• Hemoglobin ≥ 9g/dL with no blood transfusion in the past 28 days
• Total bilirubin ≤ 1.5 ULN

You may not qualify if:

• 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.
• Have used or plan concomitant use of the following medications in the past 6 months prior to enrollment: 5-alpha reductase inhibitors unless subject has been taking stable dose of medication for prior 6 months
• Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks. See the following link for a complete list of known CYP3A inhibitors: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers
• Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. See the following link for a complete list of known CYP3A inhibitors:https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers
• Have moderate or severe cardiovascular disease:
• Has the presence of cardiac disease, including a myocardial infarction within six months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension.
• Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTc prolongation \>500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• AstraZeneca: collaborator
• McGuff Pharmaceuticals, Inc.: collaborator
• The Marcus Foundation: collaborator

Study Sites (2)

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

olaparib; Ascorbic Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Results Point of Contact

• Title: Channing Paller, M.D., principal investigator
• Organization: Johns Hopkins University

cpaller1@jhmi.edu

410-955-8239

Study Officials

• Channing Paller, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2022
• First Posted: August 15, 2022
• Study Start: June 30, 2023
• Primary Completion: October 14, 2024
• Study Completion: October 14, 2024
• Last Updated: January 29, 2025
• Results First Posted: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)