MGE + ADT for Prostate Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byHeidi Klepin, MD
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: Androgen deprivation therapy
Must not be taking: Cytotoxic chemotherapy, investigational agents
Disqualifiers: Metastatic disease, recent surgery, others
Prior Safety Data
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.12345
Is the treatment MGE + ADT for prostate cancer safe?
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.211121314
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.
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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.
See 6 more
Trial 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 (Hormone Therapy)
- MGE (Other)
- Placebo (Other)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Placebo Group
Group I: MGE groupExperimental Treatment2 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 groupPlacebo Group2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Wake Forest Baptist Medical CenterWinston-Salem, NC
WG Hefner VA Medical CenterSalisbury, NC
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Who Is Running the Clinical Trial?
Wake Forest University Health SciencesLead Sponsor
References
The evolving role of androgen deprivation therapy in the management of prostate cancer. [2017]Androgen deprivation therapy (ADT) plays a central role in the management of prostate cancer. ADT is the mainstay of treatment for metastatic disease; the most common method is gonadal suppression via luteinizing hormone release hormone (LH) agonists, with or without antiandrogens. Antiandrogen monotherapy remains investigational, as is the appropriate role of 5alphareductase inhibition for prostate cancer. Intermittent ADT offers the promise of improved quality of life and reduced cost without a decrease found to date in oncologic efficacy. A growing menu of options exists for secondary androgen deprivation after disease progression on primary therapy: these include high-dose antiandrogens, estrogens, and adrenal androgen suppressants. ADT is being used with increasing frequency as primary monotherapy in patients with localized disease, but only small, nonrandomized studies of highly selected patients have been reported to date. Neoadjuvant ADT (NADT) has been demonstrated in prospective, multi-institutional trials to improve outcomes for patients with high-risk or locally advanced disease undergoing external-beam radiotherapy. Trials for patients with lower-risk, localized disease are still ongoing. Neoadjuvant therapy does not improve outcomes for patients with localized disease opting for radical prostatectomy (RP) and has not been well studied in association with brachytherapy. The side effects of ADT can be managed increasingly successfully; in particular, the introduction of zoledronate may reduce the impact of ADT-associated osteoporosis. Finally, contemporary practice pattern data suggest that use of ADT is increasing across patient risk groups, both in contexts where such therapy is well supported by current evidence and in others where it is not.
Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells. [2018]Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR.
Predictors of androgen deprivation therapy efficacy combined with prostatic irradiation: the central role of tumor stage and radiation dose. [2022]To evaluate the response of clinically localized prostate cancer to various durations of planned androgen deprivation therapy (ADT) and to investigate subgroups predicting response.
Survival and clinical metastases among prostate cancer patients treated with androgen deprivation therapy in Sweden. [2014]To examine the incidence of metastases and clinical course of prostate cancer patients who are without confirmed metastasis when initiating androgen deprivation therapy (ADT).
Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer. [2019]Although once reserved for the management of metastatic prostate cancer, androgen deprivation therapy (ADT) is being used increasingly to treat lower stages of disease. We sought to assess patterns of ADT use in a contemporary cohort of men newly diagnosed with prostate cancer. Men with newly diagnosed prostate cancer who had > or =12 months of follow-up evaluation were identified in a national disease registry of patients with prostate cancer. The patterns of ADT use, both primary and secondary, were characterized and stratified by risk according to prostate-specific antigen levels, clinical stage, and Gleason score. In a cohort of 1485 men, 46% underwent ADT at some point during their treatment: 41% as primary therapy (either sole therapy or neoadjuvant therapy), and 5% as secondary therapy. In all, 50% of men receiving initial ADT had low- or intermediate-risk disease characteristics. Among patients treated with radical prostatectomy and radiation therapy, neoadjuvant ADT was administered in 20% and 48% of patients, respectively. Secondary hormonal manipulation was observed in 5% and 7% of patients treated initially with surgery or radiation, respectively. ADT is commonly used to treat men with prostate cancer. Much of the use of ADT is in men with low- and intermediate-risk disease characteristics. The appropriateness of such therapy requires further study, including its effect, not only on disease endpoints, but also on resource utilization and health-related quality of life.
Maximal testosterone suppression in the management of recurrent and metastatic prostate cancer. [2020]Testosterone suppression, or androgen-deprivation therapy (ADT), is an established treatment for recurrent and metastatic prostate cancer (PCa). Based on the accuracy and sensitivity of early assays (c. 1960-1970), the castrate testosterone level was set at ≤1.7 nmol/l. Improved sensitivity of testosterone assays shows that both surgical and medical castration can achieve levels
Androgens and prostate cancer; pathogenesis and deprivation therapy. [2013]Although androgen receptor signaling is critical for prostate cancer growth and survival, evidence supporting a favorable risk-benefit ratio of androgen deprivation therapy (ADT) is currently limited to men with high-risk or metastatic disease. This is in part because ADT has been associated with a number of constitutional and somatic side effects, consistent with the widespread tissue expression of sex steroid receptors. ADT is the most common contemporary cause of severe hypogonadism, and men receiving this therapy represent a unique model of severe sex steroid deficiency with a defined time of onset. This review will present an update on the role of ADT in the treatment of prostate cancer, will summarize recent evidence regarding ADT-associated adverse effects with particular emphasis on cardiometabolic and musculoskeletal health, and will provide recommendations for further research.
Cardiovascular Safety of Degarelix Versus Leuprolide for Advanced Prostate Cancer: The PRONOUNCE Trial Study Design. [2022]This study will compare the incidence of major adverse cardiovascular events (MACEs) with androgen deprivation therapy (ADT) among men with advanced prostate cancer who are being treated with a gonadotropin-releasing hormone (GnRH) antagonist versus a GnRH agonist.
Androgen Deprivation Therapy and the Re-emergence of Parenteral Estrogen in Prostate Cancer. [2022]Androgen deprivation therapy (ADT) resulting in testosterone suppression is central to the management of prostate cancer (PC). As PC incidence increases, ADT is more frequently prescribed, and for longer periods of time as survival improves. Initial approaches to ADT included orchiectomy or oral estrogen (diethylstilbestrol [DES]). DES reduces PC-specific mortality, but causes substantial cardiovascular (CV) toxicity. Currently, luteinizing hormone-releasing hormone agonists (LHRHa) are mainly used; they produce low levels of both testosterone and estrogen (as estrogen in men results from the aromatization of testosterone), and many toxicities including osteoporosis, fractures, hot flashes, erectile dysfunction, muscle weakness, increased risk for diabetes, changes in body composition, and CV toxicity. An alternative approach is parenteral estrogen, it suppresses testosterone, appears to mitigate the CV complications of oral estrogen by avoiding first-pass hepatic metabolism, and avoids complications caused by estrogen deprivation. Recent research on the toxicity of ADT and the rationale for revisiting parenteral estrogen is discussed.
Parenteral estrogens for prostate cancer: can a new route of administration overcome old toxicities? [2013]Androgen deprivation therapy (ADT) is the mainstay of management of advanced-stage prostate cancer and recently has been shown to improve survival when administered in earlier stages of the disease. The oncologic benefits of ADT might be partially offset, however, by a reduction in quality of life because of adverse effects. In addition to the well-recognized adverse consequences of ADT, recent evidence suggests that ADT is associated with dyslipidemia, impaired glucose metabolism, adverse body compositional changes, and osteoporosis. Therefore, there is a pressing need to develop less toxic forms of ADT. A novel approach to this problem is the use of estrogen to induce androgen suppression. Whereas oral estrogen therapy is known to be associated with thromboembolic complications, studies of parenteral estrogen in men with prostate cancer suggest that the use of parenteral estrogen achieves target androgen suppression, does not adversely affect prothrombotic protein levels, and is not associated with adverse metabolic, skeletal, and body compositional changes when compared with conventional ADT. Herein, we review the data for parenteral estrogen use in prostate cancer, the antineoplastic mechanisms of action of estrogen in prostate cancer, the potential advantages of parenteral estrogen compared with conventional ADT, and the remaining barriers in the use of parenteral estrogen in prostate cancer.
Medical castration of males with megestrol acetate and small doses of diethylstilbestrol. [2013]An alternative program for medical castration for treatment of prostate cancer has been developed using a progestational antiandrogen, megestrol acetate (MA), in combination with small doses of diethylstilbestrol (DES; 0.1 mg/day). The administration of MA (40-80 mg/day) with 0.1 mg DES to nine patients resulted in castrate levels of plasma testosterone (less than 0.4 ng/ml) and significant suppression of both FSH and LH (P less than 0.05) for up to 12 months. Although large clinical trials must ultimately establish its safety, clinical side effects of this combined therapy to date have consisted of mild gynecomastia in two patients. The symptoms did not necessitate discontinuing the medications. It is concluded that the use of 0.1 mg DES with a minimum of 40 mg/day MA results in medical castration with sustained suppression of plasma testosterone. Because of the possible additional therapeutic advantage of blockade of intracellular androgen-mediated action by MA in androgen-dependent tumors, this combined therapy should be further explored as a possible initial treatment of choice for advanced prostate cancer.
Megestrol acetate plus low-dose estrogen in the management of advanced prostatic carcinoma. [2013]Megestrol acetate plus low-dose estrogen may be an effective, low-cost alternative to pharmacologic or surgical castration plus flutamide in the management of patients with advanced prostate cancer. The potential benefit of combined androgen ablation achieved by any means in comparison with conventional hormonal therapy appears to be limited.
Megestrol acetate plus minidose diethylstilbestrol in the treatment of carcinoma of the prostate. [2018]A multicenter randomized trial comparing megestrol acetate 120 mg/d, plus diethylstilbestrol (DES) 0.1 to 3 mg/d in patients with stage D2 prostate cancer was undertaken to compare the efficacy and toxicity of these two regimens. Pretreatment characteristics, including pathologic grade, performance status, age, and disease-related symptoms were similar in the two groups. Of 81 patients who have been entered in the study, 77 are evaluable for response and toxicity at a mean follow-up of 13.3 months. Using National Prostate Cancer Project (NPCP) criteria, no difference in response rate is noted (73% v 76%) or in disease-free survival and overall survival. The ability to suppress serum testosterone to castration levels and to maintain this suppression is equivalent in both treatment groups. However, treatment-related toxicity, including edema, hypertension, and gynecomastia, occurred at a significantly greater frequency, severity, and after a shorter treatment period in the DES-treated group. No difference in major cardiovascular events was noted. Since megestrol acetate plus minidose DES is equivalent to DES in achieving treatment responses in patients with carcinoma of the prostate, it is a preferable treatment because of its improved side-effect profile.
[Aminoglutethimide in the treatment of advanced prostatic cancer]. [2013]A total of ten previously castrated men with stage D carcinoma received 1000 mg aminoglutethimide and 50 mg/die cortisoneacetate. The patients were evaluated using the criteria of the National Prostate Cancer Project. No patients showed objective response, three patients had reduction of bone pain and subjective improvement. Pretreatment testosterone, prolactine and estradiol levels were measured. Three patients had a statistically significant elevation of testosterone levels.