Cyclophosphamide + Dexamethasone for Prostate Cancer

Overseen By Selina Laqui, MD, PhD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Rashmi Verma, MD

Must not be taking: Systemic prostate therapy

Disqualifiers: Active malignancy, Untreated infection, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 4 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a drug combination for treating prostate cancer that resists typical hormone therapy and has metastasized. Cyclophosphamide, a chemotherapy drug, stops cancer cells from growing, while dexamethasone, a steroid, can reduce chemotherapy side effects. The researchers aim to determine if these drugs, when combined, can better manage this challenging cancer. Men with metastatic prostate cancer who have tried at least two treatments and have low testosterone levels might be suitable for this study. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have used systemic therapy for prostate adenocarcinoma within 2 weeks before starting the study treatment.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that using cyclophosphamide with dexamethasone is generally safe for treating prostate cancer that no longer responds to hormone therapy. Studies using low doses of cyclophosphamide found that more than half of the patients experienced benefits, indicating that the treatment is usually well-tolerated.

Cyclophosphamide is a chemotherapy drug with manageable side effects, familiar to doctors. Dexamethasone, a steroid, helps reduce chemotherapy side effects. Together, these drugs might safely control prostate cancer. However, as this is an early phase study, the main focus is on assessing safety and side effects, making regular monitoring important. ^{1 2 3 4 5}

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

Researchers are excited about using cyclophosphamide and dexamethasone for prostate cancer because of their unique approach to treatment. Most standard treatments for prostate cancer, like hormone therapy or chemotherapy, target cancer cells directly or block hormones that fuel cancer growth. However, cyclophosphamide is an alkylating agent that works by interfering with the DNA of cancer cells, preventing them from multiplying. When combined with dexamethasone, which reduces inflammation and can enhance the effects of chemotherapy, this treatment might offer a new way to tackle cancer cells, potentially leading to more effective control of the disease.

What evidence suggests that this treatment might be an effective treatment for prostate cancer?

Research shows that combining cyclophosphamide and dexamethasone can help treat advanced prostate cancer that no longer responds to hormone therapy. Participants in this trial will receive this combination as an experimental treatment. Some studies have found this combination promising as a "salvage therapy," used when other treatments fail. For example, one study found that nearly half of the patients experienced some improvement. In another study, 85% of patients had their cancer under control temporarily. Although these results are encouraging, they remain early findings, and further research is needed to confirm them. ^{1 6 7 8 9}

Who Is on the Research Team?

Rashmi Verma, MD

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for adult men with advanced prostate cancer that has spread and resisted castration treatment. They must understand the study, follow its schedule, have certain blood and organ function levels within set limits, and have tried at least two prior treatments including one targeting hormones.

Inclusion Criteria

My scans show at least one cancer spread to another part of my body.

I can take care of myself but may not be able to do heavy physical work.

Life expectancy >= 3 months

Exclusion Criteria

I haven't had a severe infection in the last 28 days that would make it unsafe for me to join the trial.

I haven't had systemic therapy for prostate cancer in the last 2 weeks.

Any condition that would prohibit the understanding or rendering of informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cyclophosphamide and dexamethasone orally once daily on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 4 years

Monthly visits for cycle assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 3 months thereafter.

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Dexamethasone

Trial Overview The safety and side effects of combining cyclophosphamide (a chemotherapy drug) with dexamethasone (a corticosteroid) are being tested to see if they effectively treat metastatic castration-resistant prostate cancer with fewer side effects when given in low daily doses.

How Is the Trial Designed?

Group I: Treatment (cyclophosphamide, dexamethasone) Experimental Treatment 2 Interventions

Patients receive cyclophosphamide PO QD and dexamethasone PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Rashmi Verma, MD

Lead Sponsor

Trials

1

Recruited

7+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 78 patients with high-risk localized prostate cancer, the addition of neoadjuvant chemotherapy with docetaxel and estramustine (DE) did not lead to increased long-term side effects related to testosterone recovery or sexual function after androgen deprivation therapy (ADT).

After a median follow-up of 5.9 years, 78% of patients had normal testosterone levels, and 43% reported the ability to have erections without medical assistance, indicating that DE does not negatively impact recovery from ADT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Castration-related Outcomes in Patients With High-risk Localized Prostate Cancer Treated With Androgen Deprivation Therapy With or Without Docetaxel and Estramustine in the UNICANCER GETUG-12 Trial. Dumont, C., Baciarello, G., Bosset, PO., et al.[2021]

In a study of 28 advanced hormone-refractory prostate cancer patients, a novel treatment combining intravenous cyclophosphamide with an oral metronomic regimen of cyclophosphamide, celecoxib, and dexamethasone resulted in a 32% response rate, with significant decreases in prostate-specific antigen levels.

The treatment demonstrated a favorable safety profile, with no severe toxicities reported, and showed potential pharmacodynamic markers (VEGF and VE-C gene expression) that could help predict patient responses to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and pharmacodynamic evaluation of metronomic cyclophosphamide, celecoxib, and dexamethasone in advanced hormone-refractory prostate cancer. Fontana, A., Galli, L., Fioravanti, A., et al.[2015]

In a trial involving 18 patients with hormone-refractory prostate cancer, a 1-day treatment combining estramustine phosphate and docetaxel showed promising efficacy, with 7 patients experiencing over 50% declines in prostate-specific antigen levels for more than 4 weeks.

The treatment was associated with manageable toxicities, primarily grade 3 effects like neutropenia and fatigue, but no serious thromboembolic complications were observed, indicating that the regimen is relatively safe and reversible within a week.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary evaluation of a short course of estramustine phosphate and docetaxel (Taxotere) in the treatment of hormone-refractory prostate cancer. Sinibaldi, VJ., Carducci, M., Laufer, M., et al.[2018]

In a study of 125 patients with advanced prostatic cancer who had failed previous hormonal therapy, cyclophosphamide was found to be the most effective treatment, showing a 35% response rate compared to 30% for methyl-chloroethyl-cyclohexy-nitrosourea and 15% for hydroxyurea.

While methyl-chloroethyl-cyclohexy-nitrosourea and hydroxyurea demonstrated some activity, they were associated with excessive toxicity, making cyclophosphamide the preferred option due to its better balance of efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of hydroxyurea, methyl-chloroethyl-cyclohexy-nitrosourea and cyclophosphamide in patients with advanced carcinoma of the prostate. Loening, SA., Scott, WW., deKernion, J., et al.[2019]

In a study of 83 patients with hormone-resistant prostate cancer, treatment with cyclophosphamide and prednisolone resulted in objective regression of metastases in 7 patients and significant pain relief in 55 patients, with 26 reporting very good relief.

The therapy led to a notable reduction in elevated acid phosphatase levels in 11 patients, indicating some biochemical response, although most remissions lasted less than 6 months, with only 2 patients experiencing remission for over a year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclophosphamide-prednisolone therapy in advanced prostatic carcinoma. Andersson, L., Edsmyr, F., Esposti, PL., et al.[2013]

In a study of 12 patients with androgen-independent prostate cancer, dexamethasone alone did not lead to a significant reduction in prostate-specific antigen (PSA) levels, with a median PSA increase of 47%.

However, when combined with estramustine and docetaxel, 92% of patients experienced a PSA decrease of 50% or more, indicating that while dexamethasone alone is ineffective, the combination therapy is highly effective in managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone does not significantly contribute to the response rate of docetaxel and estramustine in androgen independent prostate cancer. Weitzman, AL., Shelton, G., Zuech, N., et al.[2018]

In a study of 27 patients with metastatic prostate adenocarcinoma, Cyclophosphamide alone was found to be as effective as a combination treatment of Cyclophosphamide, Adriamycin, and 5-Fluorouracil, with 53% of patients on Cyclophosphamide showing stable disease compared to 50% in the combination group.

Patients who responded to Cyclophosphamide had a significantly longer median survival of 18.6 months compared to 8.1 months for those responding to the combination therapy, indicating that Cyclophosphamide may offer better long-term outcomes despite similar efficacy in disease stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclophosphamide (NSC 26271) versus the combination of adriamycin (NSC 123127), 5-fluorouracil (NSC 19893), and cyclophosphamide in the treatment of metastatic prostatic cancer: a randomized trial. Chlebowski, RT., Hestorff, R., Sardoff, L., et al.[2019]

In a study of patients with hormone-refractory prostate cancer, a combination of low-dose cyclophosphamide and dexamethasone resulted in significant PSA reductions, with 29% of patients achieving an 80% or greater decrease in PSA levels.

The treatment was well tolerated, with manageable side effects such as bruising and gastrointestinal distress, and had a median response duration of 8 months, indicating its potential as a salvage therapy for patients who have not responded to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metronomic therapy with cyclophosphamide and dexamethasone for prostate carcinoma. Glode, LM., Barqawi, A., Crighton, F., et al.[2013]

In a phase II trial involving 33 patients, the combination of docetaxel, prednisone, and cyclophosphamide did not show a significant improvement in prostate-specific antigen decline compared to the standard treatment of docetaxel and prednisone alone.

While the combination therapy was generally well-tolerated, with no serious side effects except for some cases of leucopenia, the study's small sample size and short duration limit the ability to generalize the findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomised Phase II Trial Comparing Docetaxel Plus Prednisone with Docetaxel Plus Prednisone Plus Low-Dose Cyclophosphamide in Castration-Resistant Prostate Cancer. Porsch, M., Ulrich, M., Wendler, JJ., et al.[2021]

The first randomized trial of the National Prostatic Cancer Project showed that the combination of cytoxan and 5-FU is more effective than standard therapy for patients with hormonally resistant stage D prostate cancer.

Subsequent trials indicated that less myelosuppressive agents like estracyt and streptozotocin also provide benefits over standard treatments for previously irradiated patients, suggesting a range of effective chemotherapy options for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The chemotherapy of prostatic carcinoma. Beckley, S., Wajsman, Z., Slack, N., et al.[2013]

The first nationally randomized trial of the National Prostatic Cancer Project demonstrated that chemotherapy, specifically cyclophosphamide and 5-Fluorouracil, is more effective than standard therapy for managing advanced prostate cancer (Stage D) that has relapsed after endocrine treatment.

Additional trials have shown that estramustine phosphate and streptozotocin provide benefits over standard therapy for patients with prior radiation treatment, indicating that various chemotherapy combinations are being explored to improve outcomes in advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy Programs of the National Prostatic Cancer Project (NPCP). Schmidt, JD., Scott, WW., Gibbons, R., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05479578

Study Details | NCT05479578 | Cyclophosphamide and ... The combination of cyclophosphamide and dexamethasone may work better in treating patients with castration resistant prostate cancer. Detailed Description.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/14534880/

Metronomic therapy with cyclophosphamide and ... Low-dose dexamethasone and cyclophosphamide demonstrated efficacy as salvage therapy in the treatment of patients with hormone-refractory prostate carcinoma.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33534414/

Exceptional response to cyclophosphamide and ... Exceptional response to cyclophosphamide and dexamethasone in a patient with metastatic castrate-resistant prostate cancer and RB1 mutation.

4. hemonc.org hemonc.org/wiki/Prostate_cancer_-_historical

Prostate cancer - historical The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from ...

5. researchgate.net researchgate.net/publication/382144276_Efficacy_and_safety_of_metronomic_cyclophosphamide_combined_with_abiraterone_and_dexamethasone_in_heavily_pretreated_metastatic_castration_resistant_prostate_cancerA_retrospective_real-world_study

Efficacy and safety of metronomic cyclophosphamide ... Overall response rate (ORR) was 46% (6/13) and the disease control rate (DCR) was 85% (11/13). Median duration of response (DoR) was 3.0 months.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11892613/

Oral Cyclophosphamide for Patients With Metastatic ... When metastatic disease progresses to a castration-resistant state, the 5-year relative survival has been reported to be as low as 30%.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9147851/

Metronomic Chemotherapy for Advanced Prostate Cancer Cyclophosphamide was the most commonly used agent integrated into 27/30 (90%) of LDMC regimens. LDMC resulted in a clinical benefit rate of 56.8 ...

8. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-023-10780-y

Activity and safety of KEES - an oral multi-drug chemo ... KEES demonstrated meaningful efficacy in heavily pre-treated CRPC patients, especially those with PS 0–1 and lower baseline ALP, and had an acceptable toxicity ...

9. ascopubs.org ascopubs.org/doi/pdf/10.1200/GO-24-00464

Oral Cyclophosphamide for Patients With Metastatic ... 1 When metastatic disease progresses to a castration- resistant state, the 5-year relative survival has been reported to be as low as 30%.2 ...