Omeprazole for Prostate Cancer

(FASN Trial)

Recruiting at 1 trial location

Overseen By Study Nurse

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing if adding omeprazole, a common stomach acid reducer, can help prostate cancer patients who are not responding well to their current treatments with cabazitaxel or docetaxel. Omeprazole may block an enzyme that helps cancer cells grow, potentially making the cancer drugs more effective. Omeprazole has been widely studied for its interactions with other drugs.

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.

What data supports the effectiveness of the drug combination including Omeprazole for prostate cancer?

Docetaxel, a component of the treatment, has been shown to significantly extend survival in patients with advanced prostate cancer, and cabazitaxel has been effective in prolonging survival after docetaxel treatment. These findings suggest that the combination of these drugs may offer benefits for prostate cancer patients. ^{1 2 3 4 5}

Is cabazitaxel safe for use in humans?

Cabazitaxel has been shown to have a safety profile similar to other taxanes, with common side effects including low white blood cell counts (neutropenia) and nerve damage (neuropathy). In animal studies, changes in the bone marrow, immune system, digestive system, and male reproductive system were mostly reversible, and clinical observations in humans were consistent with these findings. ^{3 4 6 7 8}

How is the drug cabazitaxel unique for prostate cancer treatment?

Cabazitaxel is unique because it is the first drug shown to increase survival in patients with metastatic castration-resistant prostate cancer (mCRPC) who have already been treated with docetaxel, offering a new option when the cancer becomes resistant to initial treatments. ^{5 9 10 11 12}

Research Team

Michael Goodman, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

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 am 18 years old or older.

I can take care of myself and perform daily activities.

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Cabazitaxel (Fatty Acid Synthase Inhibitor)
• Docetaxel (Fatty Acid Synthase Inhibitor)
• Omeprazole (Proton Pump Inhibitor)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Findings from Research

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]

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]

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]

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]

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 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]

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, 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]

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]

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]

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 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]

References

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

New paradigms for advanced prostate cancer. [2022]

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

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

3. Australia pubmed.ncbi.nlm.nih.gov

Efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer: A single-center study in Japan. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

5. Italy 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). [2018]

6. Spain pubmed.ncbi.nlm.nih.gov

Cabazitaxel, a new taxane with favorable properties. [2017]

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

Preclinical profile of cabazitaxel. [2018]

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

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

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

Safety and efficacy of cabazitaxel in the docetaxel-treated patients with hormone-refractory prostate cancer. [2021]

10. England 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). [2020]

11. England pubmed.ncbi.nlm.nih.gov

Anti prostate cancer using PEGylated bombesin containing, cabazitaxel loading nano-sized drug delivery system. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Cabazitaxel schedules in metastatic castration-resistant prostate cancer: a review. [2021]