Olaparib + Vitamin C for Prostate Cancer

No longer recruiting at 2 trial locations

Overseen By GU oncology

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: Hormonal ablation

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: DNA repair mutation, CNS metastases, cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for advanced prostate cancer that resists standard hormone therapy. Researchers aim to determine if adding high doses of Vitamin C to the drug olaparib can safely reduce cancer activity. The trial focuses on patients whose prostate cancer progresses despite treatments like chemotherapy or radiation. Ideal participants are men with prostate cancer that has spread and is uncontrolled by current treatments, without known DNA repair gene mutations. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial requires stopping certain medications. You must stop using strong or moderate CYP3A inhibitors and inducers before starting the study. The washout period is 2 weeks for CYP3A inhibitors and 3-5 weeks for CYP3A inducers, depending on the specific drug. If you're on 5-alpha reductase inhibitors, you must have been on a stable dose for 6 months prior. Other medications may not need to be stopped, but consult with the trial team for specifics.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for some drugs. If you are taking strong or moderate CYP3A inhibitors or inducers, you will need to stop them 2 to 5 weeks before starting the study treatment. Please check with the trial team for specific guidance on your medications.

Is there any evidence suggesting that the combination of olaparib and Vitamin C is likely to be safe for humans?

Research has shown that both olaparib and high-dose vitamin C have available safety information. Olaparib, already approved for treating certain types of prostate cancer, has undergone extensive study. Some studies have found it to be generally well-tolerated, with common side effects including nausea and fatigue.

Studies have also indicated that high-dose vitamin C, particularly when administered intravenously, is usually safe. It has been tested alongside other treatments without major safety concerns.

Since this trial is in Phase 2, earlier studies have provided some safety information. This suggests that the combination of olaparib and vitamin C is considered safe enough for further testing, though researchers continue to monitor for any serious side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about the combination of Olaparib and Vitamin C for prostate cancer because it offers a unique approach compared to standard treatments like hormone therapy and chemotherapy. Olaparib is a PARP inhibitor, which targets cancer cells by preventing them from repairing their DNA, leading to cell death. This mechanism is different from traditional treatments that often attack both healthy and cancerous cells, potentially reducing side effects. Additionally, the inclusion of high-dose Vitamin C, administered intravenously, may enhance the cancer-fighting effects of Olaparib by further stressing cancer cells. Together, this combination could offer a more targeted and effective treatment option for prostate cancer patients.

What evidence suggests that the combination of Olaparib and Vitamin C could be effective for prostate cancer?

Research has shown that olaparib, a cancer treatment, offers significant benefits for prostate cancer patients. Studies have found that olaparib can extend the time patients live without their cancer worsening. In this trial, participants will receive a combination of olaparib and high-dose vitamin C to determine if this treatment can destroy more cancer cells in patients with advanced prostate cancer that no longer responds to standard hormone therapy. While olaparib works especially well for patients with certain genetic changes, researchers are testing the addition of vitamin C to see if it can benefit more people. This trial aims to determine if this combination can significantly lower PSA levels, which are used to monitor prostate cancer. ^{5 6 7 8 9}

Who Is on the Research Team?

Channing Paller, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

Men over 18 with castration-resistant prostate cancer, who have progressed after one systemic treatment. They must have a PSA of at least 1 ng/mL, good performance status (able to carry out daily activities), and normal organ/marrow function. Contraception is required for men and their partners. Exclusions include prior PARP inhibitors use, recent major surgery or chemotherapy, strong CYP3A inducers use, uncontrolled heart conditions, active hepatitis or HIV.

Inclusion Criteria

I am fully active or can carry out light work.

My condition worsened despite treatment.

Have a minimum PSA of 1 ng/mL

Exclusion Criteria

I have a mutation in my DNA repair genes.

I have cancer that has spread to my brain or spinal cord.

Known hypersensitivity to olaparib or any excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Olaparib at 300 mg by mouth, twice daily, and ascorbate at 1 g/kg IV twice weekly until disease progression or unacceptable toxicities

up to 5 years

Twice weekly visits for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 1 year 4 months

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib
• Vitamin C

Trial Overview The trial tests the combination of Olaparib (a PARP inhibitor) and high-dose IV Vitamin C in treating prostate cancer without DNA repair gene mutations. It measures the reduction in PSA levels by half from baseline as the main outcome and looks at safety through incidence of severe toxicities.

How Is the Trial Designed?

Group I: Olaparib and Vitamin C Experimental Treatment 2 Interventions

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.

Olaparib is already approved in European Union, United States for the following indications:

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

McGuff Pharmaceuticals, Inc.

Industry Sponsor

Trials

4

Recruited

130+

The Marcus Foundation

Collaborator

Trials

19

Recruited

2,200+

Published Research Related to This Trial

The combination of olaparib and radium-223 is safe for patients with metastatic castration-resistant prostate cancer (mCRPC), with a recommended phase II dose of olaparib at 200 mg taken twice daily alongside radium-223.

Early results show promising efficacy, with a 6-month radiographic progression-free survival (rPFS) rate of 58%, particularly in patients with specific HRR gene alterations, indicating potential for further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of Combination Olaparib and Radium-223 in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) with Bone Metastases (COMRADE). Pan, E., Xie, W., Ajmera, A., et al.[2023]

BRCA1 and BRCA2 mutations significantly increase the risk and aggressiveness of prostate cancer, highlighting the importance of genetic testing in prostate oncology.

Olaparib, an oral PARP inhibitor, has shown efficacy and good tolerance in phase II trials for patients with advanced castration-resistant prostate cancer, making it a promising treatment option while awaiting further phase III trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defective DNA repair mechanisms in prostate cancer: impact of olaparib. De Felice, F., Tombolini, V., Marampon, F., et al.[2018]

The combination of the c-MET inhibitor PHA665752 and the PARP inhibitor olaparib showed a synergistic effect in blocking the growth of prostate cancer cell lines, indicating enhanced therapeutic efficacy compared to using olaparib alone.

This dual treatment not only suppressed cancer cell invasion and migration but also impaired the DNA damage response, suggesting a novel mechanism that could improve treatment outcomes for prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting c-MET to Enhance the Efficacy of Olaparib in Prostate Cancer. Wang, Z., Dai, Z., Wang, B., et al.[2022]

In a phase 2 trial involving 142 patients with metastatic castration-resistant prostate cancer, the combination of olaparib and abiraterone significantly improved progression-free survival compared to placebo plus abiraterone, indicating its potential efficacy in extending patient survival.

However, exploratory analyses showed no significant differences in pain levels or health-related quality of life between the two treatment groups, suggesting that while the combination therapy may improve survival, it does not necessarily enhance the quality of life or reduce pain for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with olaparib plus abiraterone versus placebo plus abiraterone for metastatic castration-resistant prostate cancer: a randomised, double-blind, phase 2 trial. Saad, F., Thiery-Vuillemin, A., Wiechno, P., et al.[2022]

In a phase 2 trial involving 50 patients with metastatic, castration-resistant prostate cancer, treatment with the PARP inhibitor olaparib resulted in a 33% response rate, particularly among patients with DNA-repair gene defects, such as BRCA1/2 and ATM.

Among the 16 patients with identified DNA-repair defects, 88% responded to olaparib, highlighting the efficacy of this treatment in a specific subgroup of prostate cancer patients, while the most common side effects were anemia and fatigue, consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. Mateo, J., Carreira, S., Sandhu, S., et al.[2022]

Olaparib, a PARP inhibitor, has been approved for treating metastatic castration-resistant prostate cancer (mCRPC) in men with homologous recombination repair (HRR) gene mutations, which are present in about 27% of prostate cancer patients, showing improved overall survival in clinical trials.

The Phase III PROfound trial demonstrated that olaparib significantly benefits men with mCRPC who have progressed on other hormonal treatments, highlighting its role in targeted therapy based on genetic profiling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Utility of Olaparib in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Review of Current Evidence and Patient Selection. LeVee, A., Lin, CY., Posadas, E., et al.[2021]

Olaparib was found to be effective in treating metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA mutations, showing a high response rate in 89% of these patients, compared to lower response rates in those without such mutations.

While most adverse events (AEs) were manageable, common side effects included fatigue (70%), anemia (65%), and decreased appetite (55%), with some patients experiencing severe AEs, indicating that while Olaparib is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib outcomes in metastatic castration-resistant prostate cancer: First real-world experience in safety and efficacy from the Chinese mainland. Pan, J., Ye, D., Zhu, Y.[2022]

The combination of niraparib, a PARP inhibitor, with Radium-223 was found to be safe for treating metastatic castrate-resistant prostate cancer (mCRPC) in men without known BRCA mutations, with manageable dose-limiting toxicities (DLTs) primarily related to blood cell counts.

In a study of 30 patients, the maximum tolerated dose (MTD) varied based on prior chemotherapy exposure, indicating that personalized dosing may be necessary; further research is needed to explore biomarkers that could predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Niraparib in Combination with Radium-223 for the Treatment of Metastatic Castrate-Resistant Prostate Cancer. Quinn, Z., Leiby, B., Sonpavde, G., et al.[2023]

A phase II study of the PARP inhibitor olaparib confirmed its clinical benefits for cancer patients with inherited BRCA1 and BRCA2 mutations, particularly in advanced breast and ovarian cancers.

The study also provided evidence that olaparib is effective against pancreatic and prostate cancers, expanding its potential use in treating various cancer types associated with these genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib shows promise in multiple tumor types. [2014]

The combination of olaparib and abiraterone significantly improves radiographic progression-free survival and other key progression metrics in patients with metastatic castration-resistant prostate cancer, based on a meta-analysis of two randomized controlled trials involving 938 patients.

While the combination therapy shows efficacy, it is associated with a higher risk of high-grade anemia compared to monotherapy, indicating a need for careful management of treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a systematic review and meta-analysis of randomized controlled trials. Luo, Z., Zhu, B., Xu, H., et al.[2023]

Olaparib is a promising treatment for metastatic castration-resistant prostate cancer (mCRPC), particularly effective in patients with specific genetic deletions, marking a significant advancement in precision medicine for this condition.

The drug works by selectively inhibiting PARP 1 and 2, which interferes with the base excision repair pathway, and it has an acceptable safety profile, making it a valuable option for second- or third-line therapy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of Olaparib as a treatment option for metastatic castration-resistant prostate cancer. Mourmouris, P., Papatsoris, A., Dellis, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05501548

Phase II Study of PARP Inhibitor Olaparib and IV Ascorbate ... 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 ...

2. lynparza.com lynparza.com/prostate-cancer/results.html

Metastatic Prostate Cancer Treatment Results LYNPARZA used alone may give you more time without your cancer getting worse · LYNPARZA may help patients live longer compared with enzalutamide or abiraterone.

3. dukecancerinstitute.org dukecancerinstitute.org/blogs/research-shows-promising-outcomes-prostate-cancer-patients-treated-olaparib

Research Shows Promising Outcomes for Prostate Cancer ... Olaparib, a targeted therapy used to treat prostate cancer, showed significant benefits in patients with homologous recombination repair (HRR) gene mutations.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-09192

Olaparib and Ascorbic Acid for the Treatment of Metastatic ... Giving olaparib and ascorbic acid may kill more tumor cells in patients with metastatic castration-resistant prostate cancer.

5. lynparzahcp.com lynparzahcp.com/prostate-cancer/efficacy/monotherapy.html

LYNPARZA PROfound Trial for HRRm mCRPC | Efficacy Data ... Median OS with LYNPARZA was 19.1 months (95% CI: 17.4–23.4) vs 14.7 months with investigator's choice of enza or abi/pred (95% CI: 11.9–18.8).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10055378/

PARP inhibition and pharmacological ascorbate ... Over the last decade, multiple trials have demonstrated the safety of ascorbic acid alone or in combination with chemotherapy. Some studies suggest that ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10587563/

Efficacy and safety of olaparib combined with abiraterone ... Olaparib has been proven for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This meta-analysis aims to ...

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/48/NCT05501548/Prot_SAP_000.pdf

Phase II Study of PARP Inhibitor Olaparib and IV Ascorbate ... This trial seeks to assess the combination of olaparib and IV ascorbic acid in men with castration resistant prostate cancer. There is no ...

9. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2200043

Abiraterone and Olaparib for Metastatic Castration-Resistant ... The safety profile of olaparib and abiraterone was consistent with the known safety profiles of the individual drugs. The most common adverse ...