Olaparib + Vitamin C for Prostate Cancer

Recruiting at 1 trial location

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

4 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a combination of a drug that stops cancer cells from fixing themselves and high doses of vitamin C in prostate cancer patients who do not respond to standard hormone therapy and lack certain genetic mutations. The goal is to see if this combination can reduce cancer markers and improve survival.

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 the combination of Olaparib and Vitamin C safe for humans?

Olaparib has been studied for safety in combination with other treatments for prostate cancer, showing common side effects like fatigue and anemia. However, there is no specific safety data available for the combination of Olaparib and Vitamin C. ^{1 2 3 4 5}

What safety data is available for the combination of Olaparib and Vitamin C in prostate cancer treatment?

The provided research does not directly address the safety of the combination of Olaparib and Vitamin C for prostate cancer. However, it includes safety data for Olaparib in combination with other treatments like Radium-223 and Abiraterone. In these studies, common adverse events for Olaparib included fatigue and anemia. No specific safety data for the combination with Vitamin C is mentioned. ^{1 2 3 4 5}

Is the drug Olaparib a promising treatment for prostate cancer?

Yes, Olaparib is a promising drug for treating prostate cancer, especially for patients with specific genetic mutations. It works by targeting cancer cells' DNA repair process, leading to their death. Studies have shown that it can improve survival rates and is considered a valuable option for patients with advanced prostate cancer. ^{3 6 7 8 9}

What makes the drug Olaparib combined with Vitamin C unique for prostate cancer treatment?

Olaparib is a unique drug for prostate cancer because it targets DNA repair mechanisms, specifically in patients with certain genetic mutations, and combining it with Vitamin C could potentially enhance its effectiveness by further disrupting cancer cell survival. ^{3 6 7 8 9}

What data supports the idea that Olaparib + Vitamin C for Prostate Cancer is an effective treatment?

The available research does not provide specific data on the effectiveness of Olaparib combined with Vitamin C for prostate cancer. However, studies show that Olaparib, when used with other treatments like radium-223 or abiraterone, can be effective for prostate cancer. For example, a study found that patients with metastatic castration-resistant prostate cancer had improved progression-free survival when treated with Olaparib and abiraterone compared to a placebo. This suggests that Olaparib can be beneficial in treating prostate cancer, but there is no direct evidence for its combination with Vitamin C. ^{1 3 8 10 11}

What data supports the effectiveness of the drug Olaparib for prostate cancer?

Research shows that Olaparib, a drug that blocks cancer cells from repairing their DNA, has been effective in treating prostate cancer, especially in patients with specific genetic mutations. In studies, it has improved progression-free survival, meaning patients lived longer without the cancer getting worse. ^{1 3 8 10 11}

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. United States 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). [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Phase I Study of Niraparib in Combination with Radium-223 for the Treatment of Metastatic Castrate-Resistant Prostate Cancer. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. [2022]

4. England 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. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Defective DNA repair mechanisms in prostate cancer: impact of olaparib. [2018]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Targeting c-MET to Enhance the Efficacy of Olaparib in Prostate Cancer. [2022]

7. Switzerland 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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Olaparib shows promise in multiple tumor types. [2014]

9. England pubmed.ncbi.nlm.nih.gov

Overview of Olaparib as a treatment option for metastatic castration-resistant prostate cancer. [2022]

10. New Zealand 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. [2021]

11. Korea (South) 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. [2022]