Omeprazole for Prostate Cancer

(FASN Trial)

Recruiting at 1 trial location

Overseen By Study Nurse

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must be taking: Taxanes

Must not be taking: Investigational agents

Disqualifiers: Infection, Heart failure, Angina, 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

Compensation: Varies

Number of Visits: 1

Duration: Up to approximately 2 years

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether omeprazole, a medication commonly used to reduce stomach acid, can enhance the effectiveness of the cancer treatments cabazitaxel or docetaxel for prostate cancer. It targets men whose prostate cancer does not respond to hormone therapy and who have already tried treatments like cabazitaxel or docetaxel. Participants should have prostate cancer that progresses despite treatment and should have previously tried taxane treatments. The study aims to assess both the positive and negative effects of adding omeprazole to the usual care. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot be on any other investigational drugs while participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that omeprazole, a medicine that reduces stomach acid, may pose risks with long-term use. Some studies suggest it might increase the risk of certain cancers, such as biliary tract cancer. However, no evidence indicates it affects PSA levels, which are sometimes linked to prostate health.

Cabazitaxel and docetaxel are chemotherapy drugs used to treat prostate cancer. Extensive information exists about their safety due to their long-term use. Patients taking these drugs have experienced side effects like low blood cell counts and tiredness, but these are well-known and closely monitored during treatment.

This trial is in Phase 2, indicating that the treatment has passed initial safety tests, but researchers are still assessing how well participants tolerate it. Participants can expect careful monitoring for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the use of omeprazole for prostate cancer because it offers a novel approach compared to the typical chemotherapy options like cabazitaxel and docetaxel. Unlike these standard treatments, which primarily target cell division, omeprazole is known for its role in reducing stomach acid but is being repurposed here to potentially influence tumor microenvironments or cancer cell metabolism. This unique angle could lead to new ways of enhancing the effectiveness of existing treatments or improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that omeprazole may have both beneficial and adverse effects on prostate cancer. Some studies suggest it might slow tumor growth by blocking certain enzymes, while others indicate it could promote cancer growth by increasing certain proteins. This trial tests omeprazole alongside standard treatments, including cabazitaxel and docetaxel, which are proven to stop cancer cells from dividing. Researchers hope omeprazole could enhance the effectiveness of these drugs, but further research is needed to confirm this. Overall, uncertainty remains about omeprazole's effectiveness in treating prostate cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Michael Goodman, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's gotten worse despite hormone therapy and previous taxane treatment (like docetaxel). They must be fairly active, have good organ function, expect to live more than 2 months, and agree to use birth control. Can't join if they're on other experimental drugs or have serious health issues like heart failure or uncontrolled infections.

Inclusion Criteria

I can take care of myself and perform daily activities.

I can understand and am willing to sign the consent form.

My cancer has worsened according to specific criteria.

Exclusion Criteria

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

Patients may not be receiving any other investigational agents

I am allergic to medications similar to omeprazole or taxanes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive omeprazole in combination with cabazitaxel or docetaxel on an outpatient basis

Up to approximately 2 years

Cycle 1 Day 1 (baseline), Cycle 5 Day 1, and Day 1 of every subsequent cycle (each cycle is 28 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cabazitaxel
• Docetaxel
• Omeprazole

Trial Overview The trial is testing the effects of omeprazole combined with cabazitaxel or docetaxel chemotherapy on men with castration-resistant prostate cancer. The goal is to see if omeprazole can enhance the effectiveness of chemotherapy.

How Is the Trial Designed?

Group I: Omeprazole Plus Standard of Care for Prostate Cancer Regimen Experimental Treatment 1 Intervention

This intervention will be given on an outpatient basis. Omeprazole, 80 mg twice daily.

Cabazitaxel is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jevtana for:

• Hormone refractory metastatic prostate cancer

Approved in United States as Jevtana for:

• Metastatic castration-resistant prostate cancer

Approved in Canada as Jevtana for:

• Hormone-refractory metastatic prostate cancer

Approved in Japan as Jevtana for:

• Prostate cancer

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Docetaxel-based therapy has been shown to provide a survival benefit for men with metastatic prostate cancer, marking a significant advancement beyond palliative care options.

Ongoing trials are exploring various combination therapies with docetaxel, but the best timing for initiating treatment remains unclear due to a lack of prospective clinical trial data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role of chemotherapy in metastatic hormone-refractory prostate cancer. Petrylak, DP.[2022]

The study developed bombesin-targeted lipid-polymer hybrid nanoparticles (BN-CAB-LPNs) for delivering cabazitaxel to prostate cancer cells, showing effective targeting and enhanced drug delivery.

In vitro and in vivo tests demonstrated that BN-CAB-LPNs significantly inhibited the growth of prostate cancer cells and exhibited superior anti-tumor activity compared to other formulations, indicating their potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti prostate cancer using PEGylated bombesin containing, cabazitaxel loading nano-sized drug delivery system. Chen, W., Guo, M., Wang, S.[2022]

Cabazitaxel is an effective treatment for patients with taxane-resistant metastatic breast cancer and metastatic castration-resistant prostate cancer, showing significant clinical activity in these populations.

In the TROPIC phase III trial, cabazitaxel combined with prednisone significantly improved overall survival compared to mitoxantrone/prednisone in patients previously treated with docetaxel, leading to its FDA approval in 2010.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel, a new taxane with favorable properties. Bouchet, BP., Galmarini, CM.[2017]

Docetaxel is the first treatment to significantly improve survival rates in patients with hormone-refractory prostate cancer, and it is now being tested in earlier stages of the disease to prevent recurrence in high-risk patients.

Pilot studies indicate that using docetaxel as a neo-adjuvant treatment can be done safely without increasing surgical risks, and ongoing randomized trials will further assess its effectiveness when combined with hormonal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-risk localized prostate cancer: integrating chemotherapy. Oh, WK.[2018]

Docetaxel-based therapy has been shown to provide a significant survival benefit (20% to 24%) for men with metastatic hormone-refractory prostate cancer compared to previous treatments, leading to its FDA approval.

Ongoing clinical trials are exploring combinations of docetaxel with other therapies, including those targeting bone and tumor vasculature, as well as immune therapies, to improve treatment outcomes and define optimal treatment sequencing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New paradigms for advanced prostate cancer. Petrylak, DP.[2022]

Cabazitaxel is an effective second-line chemotherapy for metastatic castration-resistant prostate cancer, but it carries a risk of neutropenic complications, especially in frail elderly patients.

Using prophylactic granulocyte colony-stimulating factor from the first treatment cycle can help improve the safety and efficacy of cabazitaxel, and alternative dosing schedules are being explored to benefit frail patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel schedules in metastatic castration-resistant prostate cancer: a review. Pobel, C., Auclin, E., Procureur, A., et al.[2021]

Cabazitaxel, a second-generation taxane, shows similar effectiveness to docetaxel in taxane-sensitive cancers but significantly outperforms it in cancers that are resistant to taxanes, indicating its potential for patients who have not responded to first-line treatments.

In preclinical studies, cabazitaxel demonstrated greater antitumor activity in central nervous system and pediatric tumor models compared to docetaxel, suggesting it could be a valuable treatment option for these challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical profile of cabazitaxel. Vrignaud, P., Semiond, D., Benning, V., et al.[2018]

Cabazitaxel is an effective treatment for metastatic Castrate Resistant Prostate Cancer (mCRPC) in patients who have progressed after docetaxel, with a median overall survival of 10.6 months and median progression-free survival of 7.7 months based on a study of 103 patients.

The treatment was associated with significant hematological toxicities, including neutropenia in 28.2% of patients, indicating that while cabazitaxel is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of cabazitaxel chemotherapy for metastatic castration-resistant prostatic carcinoma on Turkish patients (The Anatolian Society of Medical Oncology). Süner, A., Aydın, D., Hacıoğlu, MB., et al.[2018]

Cabazitaxel is a potent tubulin-binding taxane drug that has been shown to prolong survival in men with metastatic castration-resistant prostate cancer (CRPC) after treatment with docetaxel, marking it as a significant advancement in therapy.

The review highlights that cabazitaxel is the first treatment specifically effective in extending survival for patients who have progressed after docetaxel-based regimens, emphasizing its role in the management of advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of cabazitaxel in the docetaxel-treated patients with hormone-refractory prostate cancer. Calcagno, F., Nguyen, T., Dobi, E., et al.[2021]

Cabazitaxel, when combined with prednisone, significantly improves overall survival in patients with hormone-refractory metastatic prostate cancer who have previously been treated with docetaxel, as shown in the pivotal TROPIC trial.

The treatment also enhances progression-free survival and response rates for tumor and PSA levels, while maintaining an acceptable safety profile, with common side effects including hematological issues and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel: a guide to its use in hormone-refractory metastatic prostate cancer. Keating, GM.[2021]

In a trial involving 21 men with metastatic castration-resistant prostate cancer, the combination of high-dose pantoprazole and docetaxel was found to be tolerable, with no toxic deaths reported, but it did not achieve the desired efficacy, as only 52% of participants showed a significant decline in PSA levels.

The study indicated that while the treatment was safe, it did not meet the predefined response criteria to justify further testing, reinforcing that no combination regimen has yet shown superior efficacy compared to docetaxel alone in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pantoprazole Affecting Docetaxel Resistance Pathways via Autophagy (PANDORA): Phase II Trial of High Dose Pantoprazole (Autophagy Inhibitor) with Docetaxel in Metastatic Castration-Resistant Prostate Cancer (mCRPC). Hansen, AR., Tannock, IF., Templeton, A., et al.[2020]

In a study of 57 patients with metastatic castration-resistant prostate cancer treated with cabazitaxel, the median overall survival was 10.5 months, indicating that cabazitaxel can prolong survival after previous docetaxel treatment.

Key prognostic factors for poor outcomes included a poor performance status, low hemoglobin levels, and a high neutrophil-lymphocyte ratio, which can help identify patients who may benefit more from cabazitaxel therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer: A single-center study in Japan. Yamamoto, Y., Ishii, M., Yoshimura, A., et al.[2023]

Citations

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Association between the use of proton pump inhibitors and ... Contrary to the available data in the context of PCa, we found no evidence of increased PSA levels in PPI users with no prostate malignancy.

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ASCO GU 2020: The Deleterious Association Between ... In prostate cancer patients, use of PPIs was associated with increased prostate cancer-specific mortality (PCSM); The reported potential long- ...

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Proton Pump Inhibitors and Cancer: Current State of Play - PMC Results: PPIs may have pro-tumor activity by increasing plasma gastrin levels or anti-tumor activity by inhibiting V-ATPases. However, their ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0304383519301065

Proton pump inhibitors promote the growth of androgen- ... Specifically, omeprazole (OME) promoted cell cycle progression, increased c-Myc expression, ErbB2 activity and PSA secretion. Furthermore, OME induced the ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/pros.24769?af=R

Impact of proton pump inhibitors on the efficacy ... This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC).

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Proton Pump Inhibitors and Cancer Risk - PubMed Central - NIH Our review indicates that prolonged PPI use (exceeding three months) is significantly associated with an elevated risk of cancer.

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Individualized prevention of proton pump inhibitor related ... In the past 2 years alone, epidemiological studies, for the first time, linked PPI use to increased risk of biliary tract cancer, rheumatoid ...

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Proton Pump Inhibitors and Cancer: Current State of Play Proton pump inhibitors may interact with the cancer microbiome and various antineoplastic agents, such as oral and intravenous chemotherapy, tyrosine kinase ...