MGE + ADT for Prostate Cancer

Recruiting at 1 trial location

Overseen By Katherine Pleasant

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must be taking: Androgen deprivation therapy

Must not be taking: Cytotoxic chemotherapy, investigational agents

Disqualifiers: Metastatic disease, recent surgery, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 75

Duration: 12 months

160 Participants Needed

Trial Summary

What is the purpose of this trial?

It is estimated that one-third of the more than 7 million deaths from cancer worldwide are attributable to potentially modifiable risk factors, with 374,000 deaths preventable through diet modification alone. Diet supplementation for the prevention or treatment of cancer is attractive, as implementation is relatively easy, even in populations with reduced incomes and resources. Grape extracts or active components isolated from grapes have received attention as chemopreventive or therapeutic agents based upon their anti-proliferative, anti-inflammatory, and anti-oxidant properties. Evidence from preclinical trials also suggests that muscadine grape products may decrease systemic inflammation. This study builds upon promising preclinical and clinical evidence to determine if the addition muscadine grape extract (MGE) to androgen deprivation therapy (ADT) improves symptoms in men with prostate cancer.

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

The trial does not specify if you need to stop taking your current medications, but you must continue androgen deprivation therapy (ADT) if you are already on it. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment MGE + ADT for prostate cancer?

Research shows that androgen deprivation therapy (ADT) can enhance the immune system's ability to recognize and attack prostate cancer cells, especially when combined with other treatments like vaccines. This suggests that combining ADT with other therapies may improve its effectiveness against prostate cancer. ^{1 2 3 4 5}

Is the treatment MGE + ADT for prostate cancer safe?

Androgen deprivation therapy (ADT), a part of the treatment, is known to have side effects like hot flashes, muscle weakness, and increased risk for heart issues and diabetes. However, using parenteral estrogen with ADT might reduce some of these risks, especially heart-related ones. ^{6 7 8 9 10}

How does the MGE + ADT treatment for prostate cancer differ from other treatments?

The MGE + ADT treatment for prostate cancer is unique because it combines androgen deprivation therapy (ADT), which reduces male hormone levels, with megestrol acetate and low-dose estrogen, offering a potential low-cost alternative to traditional hormone therapies with a potentially better side-effect profile. ^{2 11 12 13 14}

Research Team

Heidi Klepin, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

This trial is for English-speaking men over 18 with prostate cancer who are on androgen deprivation therapy (ADT) and expected to continue it for the next year. They must have normal organ function, be able to walk, cooperate with study activities, use contraception, and sign a consent form. Men with symptomatic metastatic disease, recent surgery or radiation, rising PSA levels while on current therapy, plans to stop ADT or start chemotherapy within a year can't join.

Inclusion Criteria

I can walk, even if I need a device to help me.

I am a man, 18 or older, and speak English fluently.

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

Exclusion Criteria

I plan to stop hormone therapy or start chemotherapy within a year of joining the study.

You are currently taking any other experimental cancer treatments.

I have painful cancer spread that needs treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive muscadine grape extract or placebo orally twice daily for 12 months

12 months

Regular visits for monitoring every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-up at 72 hours post-treatment and regular visits up to 12 months

Treatment Details

Interventions

• ADT
• MGE
• Placebo

Trial Overview The trial tests if adding muscadine grape extract (MGE), known for its anti-inflammatory and antioxidant properties, to standard ADT improves symptoms in men with prostate cancer. Participants will either receive MGE or a placebo alongside their ongoing ADT treatment.

Participant Groups

Group I: MGE group Experimental Treatment 2 Interventions

Patients will be randomized to muscadine grape extract (MGE). The patients will take 4 capsules by mouth BID (twice daily). Androgen deprivation therapy (ADT) is to be started within 60 days prior to initiation of MGE.

Group II: Placebo group Placebo Group 2 Interventions

Patients will be randomized to placebo. The patients will take 4 capsules by mouth BID (twice daily). Androgen deprivation therapy (ADT) is to be started within 60 days prior to initiation of placebo.

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

Approved in European Union as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in United States as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in Canada as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in Japan as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in China as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in Switzerland as Androgen Deprivation Therapy for:

• Prostate Cancer

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Findings from Research

Androgen deprivation therapy (ADT) is essential for managing metastatic prostate cancer, primarily through gonadal suppression, and has shown promise in improving quality of life without compromising oncologic efficacy, especially with intermittent ADT.

Neoadjuvant ADT has been proven to enhance outcomes for high-risk patients undergoing radiotherapy, but it does not benefit those opting for radical prostatectomy, highlighting the need for further research in lower-risk localized disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of androgen deprivation therapy in the management of prostate cancer. Cooperberg, MR., Small, EJ., D'Amico, A., et al.[2017]

Androgen deprivation therapy (ADT) not only reduces testosterone levels but also increases androgen receptor (AR) expression in prostate cancer cells, which can enhance the immune system's ability to recognize and attack these cancer cells.

Combining ADT with a DNA vaccine targeting the AR significantly improved antitumor responses in mouse models, suggesting that this strategy may effectively overcome resistance mechanisms associated with AR overexpression in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells. Olson, BM., Gamat, M., Seliski, J., et al.[2018]

In a study of 3,666 prostate cancer patients, increasing the duration of androgen deprivation therapy (ADT) significantly reduced the risk of biochemical failure, with 6 months resulting in a 38% reduction and 12 months leading to a 58% reduction.

Patients with higher T stage cancers and those receiving lower radiation doses benefited more from longer ADT durations, suggesting that individual patient characteristics can help predict the effectiveness of ADT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of androgen deprivation therapy efficacy combined with prostatic irradiation: the central role of tumor stage and radiation dose. Williams, S., Buyyounouski, M., Kestin, L., et al.[2022]

In a study of prostate cancer patients starting androgen deprivation therapy (ADT) without confirmed metastasis, the 5-year cumulative incidence of metastasis was found to be 18%, with a survival rate of 60% over the same period.

Higher serum prostate-specific antigen (PSA) levels and shorter PSA doubling times (especially ≤ 6 months) were identified as significant predictors of increased risk for metastasis and death, highlighting the importance of monitoring these markers in patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival and clinical metastases among prostate cancer patients treated with androgen deprivation therapy in Sweden. Banefelt, J., Liede, A., Mesterton, J., et al.[2014]

In a study of 1485 men with newly diagnosed prostate cancer, 46% received androgen deprivation therapy (ADT), with 41% using it as primary treatment, indicating its growing use even in lower-risk cases.

Half of the men who started ADT had low- or intermediate-risk disease, suggesting that while ADT is common, its appropriateness for these patients needs further investigation regarding its impact on health outcomes and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer. Meng, MV., Grossfeld, GD., Sadetsky, N., et al.[2019]

Achieving a testosterone level of ≤0.7 nmol/l during androgen-deprivation therapy (ADT) is associated with improved survival outcomes in prostate cancer patients, based on a review of both prospective and retrospective studies.

Monitoring both testosterone and prostate-specific antigen (PSA) levels is crucial for assessing treatment effectiveness and determining the progression towards castration-resistant prostate cancer (CRPC).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maximal testosterone suppression in the management of recurrent and metastatic prostate cancer. Klotz, L., Breau, RH., Collins, LL., et al.[2020]

Androgen deprivation therapy (ADT) is crucial for treating prostate cancer, particularly in high-risk or metastatic cases, but its benefits are not well-established for all patients due to significant side effects.

ADT can lead to severe hypogonadism and various adverse effects, especially impacting cardiometabolic and musculoskeletal health, highlighting the need for further research on its risk-benefit ratio.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgens and prostate cancer; pathogenesis and deprivation therapy. Grossmann, M., Cheung, AS., Zajac, JD.[2013]

The PRONOUNCE trial is a significant study involving approximately 900 men with advanced prostate cancer and pre-existing cardiovascular disease, comparing the cardiovascular safety of the GnRH antagonist degarelix versus the GnRH agonist leuprolide over 12 months.

This study aims to determine if using a GnRH antagonist reduces the risk of major adverse cardiovascular events (MACEs) compared to a GnRH agonist, addressing concerns about increased cardiovascular risks associated with androgen deprivation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Safety of Degarelix Versus Leuprolide for Advanced Prostate Cancer: The PRONOUNCE Trial Study Design. Melloni, C., Slovin, SF., Blemings, A., et al.[2022]

Androgen deprivation therapy (ADT) is crucial for managing prostate cancer, but traditional methods like orchiectomy and oral estrogen can lead to significant cardiovascular toxicity and other side effects.

Parenteral estrogen may be a safer alternative to oral estrogen for ADT, as it effectively suppresses testosterone while potentially reducing cardiovascular complications and avoiding issues related to estrogen deprivation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen Deprivation Therapy and the Re-emergence of Parenteral Estrogen in Prostate Cancer. Phillips, I., Shah, SI., Duong, T., et al.[2022]

Androgen deprivation therapy (ADT) is effective for managing advanced prostate cancer but can lead to significant quality of life issues due to adverse effects like dyslipidemia and osteoporosis.

Parenteral estrogen therapy may provide a safer alternative to conventional ADT, achieving effective androgen suppression without the negative metabolic and skeletal side effects associated with traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parenteral estrogens for prostate cancer: can a new route of administration overcome old toxicities? Lycette, JL., Bland, LB., Garzotto, M., et al.[2013]

The combination of megestrol acetate (MA) and a low dose of diethylstilbestrol (DES) effectively achieved castrate levels of testosterone in nine prostate cancer patients for up to 12 months, indicating its potential as a medical castration method.

While mild side effects like gynecomastia were observed in two patients, they did not require stopping the treatment, suggesting that this therapy may be safe and warrants further investigation as a primary treatment for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical castration of males with megestrol acetate and small doses of diethylstilbestrol. Geller, J., Albert, J., Yen, SS., et al.[2013]

Megestrol acetate combined with low-dose estrogen may serve as an effective and cost-efficient alternative to traditional treatments like pharmacologic or surgical castration with flutamide for advanced prostate cancer.

The study suggests that while combined androgen ablation can be beneficial, its advantages over standard hormonal therapies are limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Megestrol acetate plus low-dose estrogen in the management of advanced prostatic carcinoma. Geller, J.[2013]

In a study of 81 patients with stage D2 prostate cancer, megestrol acetate combined with low-dose diethylstilbestrol (DES) showed similar efficacy to DES alone in terms of response rates and survival outcomes, with both treatments effectively suppressing testosterone levels.

However, the megestrol acetate regimen had a significantly better safety profile, with fewer and less severe side effects compared to the DES group, making it a preferable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Megestrol acetate plus minidose diethylstilbestrol in the treatment of carcinoma of the prostate. Venner, PM., Klotz, PG., Klotz, LH., et al.[2018]

In a study involving ten previously castrated men with advanced prostate cancer, treatment with 1000 mg of aminoglutethimide and 50 mg of cortisone acetate did not result in any objective responses, indicating limited efficacy of this combination therapy.

However, three patients reported a reduction in bone pain and subjective improvement, and three patients experienced a significant increase in testosterone levels, suggesting that while the treatment may not be effective in tumor response, it could have some impact on pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Aminoglutethimide in the treatment of advanced prostatic cancer]. Bauer, HW., Schmeller, NT., Schmiedt, E.[2013]

References

1. Italy pubmed.ncbi.nlm.nih.gov

The evolving role of androgen deprivation therapy in the management of prostate cancer. [2017]

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

Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells. [2018]

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

Predictors of androgen deprivation therapy efficacy combined with prostatic irradiation: the central role of tumor stage and radiation dose. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Survival and clinical metastases among prostate cancer patients treated with androgen deprivation therapy in Sweden. [2014]

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

Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer. [2019]

6. Canada pubmed.ncbi.nlm.nih.gov

Maximal testosterone suppression in the management of recurrent and metastatic prostate cancer. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Androgens and prostate cancer; pathogenesis and deprivation therapy. [2013]

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

Cardiovascular Safety of Degarelix Versus Leuprolide for Advanced Prostate Cancer: The PRONOUNCE Trial Study Design. [2022]

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

Androgen Deprivation Therapy and the Re-emergence of Parenteral Estrogen in Prostate Cancer. [2022]

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

Parenteral estrogens for prostate cancer: can a new route of administration overcome old toxicities? [2013]

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

Medical castration of males with megestrol acetate and small doses of diethylstilbestrol. [2013]

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

Megestrol acetate plus low-dose estrogen in the management of advanced prostatic carcinoma. [2013]

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

Megestrol acetate plus minidose diethylstilbestrol in the treatment of carcinoma of the prostate. [2018]

14. Germany pubmed.ncbi.nlm.nih.gov

[Aminoglutethimide in the treatment of advanced prostatic cancer]. [2013]