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

7 Participants Needed

Trial Summary

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.

What data supports the idea that Cyclophosphamide + Dexamethasone for Prostate Cancer is an effective drug?

The available research shows that Cyclophosphamide is effective in treating advanced prostate cancer. In one study, Cyclophosphamide alone was as effective as a combination of drugs, with patients responding to Cyclophosphamide having a longer survival time (18.6 months) compared to those on the combination treatment (8.1 months). Another study found that Cyclophosphamide had a 35% response rate, which was higher than other drugs tested. These results suggest that Cyclophosphamide is a strong option for treating advanced prostate cancer, especially in terms of survival and response rates. ^{1 2 3 4 5}

What safety data exists for Cyclophosphamide and Dexamethasone in prostate cancer treatment?

The safety data for Cyclophosphamide and Dexamethasone in prostate cancer treatment includes studies evaluating their efficacy and toxicity. One study assessed the continuous oral administration of Cyclophosphamide and Dexamethasone, noting its use in patients with PSA progression despite hormone therapy. Another study evaluated a regimen combining Cyclophosphamide, Celecoxib, and Dexamethasone, focusing on advanced hormone-refractory prostate cancer. These studies provide insights into the clinical activity and pharmacodynamic profile of these drugs, although specific safety outcomes are not detailed in the abstracts provided. ^{2 6 7 8 9}

Is the drug Cyclophosphamide a promising treatment for prostate cancer?

Yes, Cyclophosphamide shows promise as a treatment for prostate cancer. Studies indicate it can be effective alone or in combination with other drugs, providing benefits like longer survival and pain relief for some patients. ^{3 4 7 10 11}

What is the purpose of this trial?

This phase I trial tests the safety and side effects of cyclophosphamide given together with dexamethasone in treating patients with castration resistant prostate cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving low doses of cyclophosphamide daily may reduce side effects. Dexamethasone is a corticosteroid drug that is used to treat some of the problems caused by chemotherapy treatment. The combination of cyclophosphamide and dexamethasone may work better in treating patients with castration resistant prostate cancer.

Research Team

Rashmi Verma, MD

Principal Investigator

University of California, Davis

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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 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 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 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 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]

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]

References

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

Dexamethasone does not significantly contribute to the response rate of docetaxel and estramustine in androgen independent prostate cancer. [2018]

2. England pubmed.ncbi.nlm.nih.gov

The chemotherapy of prostatic carcinoma. [2013]

3. United States 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. [2019]

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

Chemotherapy Programs of the National Prostatic Cancer Project (NPCP). [2019]

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

A comparison of hydroxyurea, methyl-chloroethyl-cyclohexy-nitrosourea and cyclophosphamide in patients with advanced carcinoma of the prostate. [2019]

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

Clinical and pharmacodynamic evaluation of metronomic cyclophosphamide, celecoxib, and dexamethasone in advanced hormone-refractory prostate cancer. [2015]

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

Metronomic therapy with cyclophosphamide and dexamethasone for prostate carcinoma. [2013]

8. United States 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. [2021]

9. United States 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. [2018]

10. Switzerland 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. [2021]

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

Cyclophosphamide-prednisolone therapy in advanced prostatic carcinoma. [2013]