Lifestyle Changes and Medications for Prostate Cancer

(RADICALPC Trial)

Recruiting at 64 trial locations

Overseen By Steven Agapay, BSc

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: McMaster University

Must be taking: Androgen deprivation therapy

Must not be taking: Statins

Disqualifiers: Under 45, Bladder cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3-5 years

6000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how lifestyle changes and medications can assist men newly diagnosed with prostate cancer. The study divides participants into two groups: one group receives advice on diet, exercise, and quitting smoking, along with medications like statins (such as Simvastatin) and ACE inhibitors (a type of blood pressure medication); the other group receives standard care. Men diagnosed with prostate cancer within the past year or starting treatment with androgen deprivation therapy are encouraged to consider joining. The trial aims to determine if these interventions can improve health outcomes for prostate cancer patients. As an unphased trial, it offers participants the opportunity to contribute to valuable research that could enhance future prostate cancer care.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that ACE inhibitors, commonly used to treat high blood pressure, are generally safe. Some individuals might experience a dry cough or dizziness. Aspirin, often used to reduce inflammation, is also well-tolerated, though it can sometimes cause an upset stomach.

Research has shown that regular exercise is linked to better health and is safe for most people. Improving diet by eating more fruits and vegetables is widely considered safe and beneficial. Simvastatin, a medication used to lower cholesterol, generally has a good safety record but may occasionally cause muscle pain or digestive issues. Quitting smoking with the help of nicotine patches or gums is safe and can greatly improve health.

Overall, these treatments are usually well-tolerated, but some side effects may occur. It is important to consult a doctor about any concerns before starting a new treatment plan. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it takes a holistic approach to managing prostate cancer, focusing not just on medication but also on lifestyle changes. Unlike the standard of care, which often centers around surgery, radiation, or hormone therapies, this approach combines cardiovascular medications like ACE inhibitors and statins with lifestyle modifications such as exercise, nutrition, and smoking cessation. This comprehensive strategy aims to address the overall health of patients, potentially reducing cancer progression and improving quality of life. By integrating these elements, the trial seeks to uncover how lifestyle and medication can work together to benefit prostate cancer patients.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

This trial will compare a systematic cardiovascular and lifestyle risk factor modification strategy with usual clinical care for managing prostate cancer. Research has shown that several treatments may help manage prostate cancer. Participants in the intervention arm will receive advice on exercise and nutrition, which can enhance quality of life and may slow cancer progression. They will also receive guidance on quitting smoking, which can improve survival rates and overall health. Additionally, medications such as ACE inhibitors, often used to treat high blood pressure, might help reduce bladder problems after radiotherapy. Aspirin, known for reducing inflammation, has been linked to a lower risk of prostate cancer and better outcomes after treatment. Simvastatin, a drug that lowers cholesterol, has shown a decrease in death rates specific to prostate cancer and might reduce the chance of the cancer returning after surgery or radiation. ^{3 6 7 8 9}

Who Is on the Research Team?

Dr. Darryl Leong, MBBs,MPH,PhD,FRACP,FESC

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

Men recently diagnosed with prostate cancer or starting Androgen Deprivation Therapy can join. It's not for those under 45, seeing a cardiologist yearly, on statins with low blood pressure, or whose cancer was found after bladder surgery.

Inclusion Criteria

I am a man newly diagnosed with prostate cancer or starting hormone therapy soon.

Exclusion Criteria

I see a cardiologist yearly or take a statin with blood pressure ≤130mmHg.

I am over 45, willing to consent, and my prostate cancer was not found by accident after bladder surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a systematic cardiovascular and lifestyle risk factor modification strategy, including dietary and exercise advice, advice to quit smoking, and the prescription of open-label statins, ACE-I, and other antihypertensive medications where appropriate

3-5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on cardiovascular and prostate cancer outcomes

3-5 years

What Are the Treatments Tested in This Trial?

Interventions

• ACE inhibitor
• Aspirin
• Exercise
• Nutrition
• Simvastatin
• Smoking Cessation

Trial Overview The RADICAL PC2 trial tests a systematic approach to improve heart health and lifestyle in men newly diagnosed with prostate cancer through medications like statins and ACE inhibitors, plus exercise, diet changes, and smoking cessation.

How Is the Trial Designed?

Group I: Randomized - Intervention Active Control 5 Interventions

The intervention will consist of a systematic cardiovascular and lifestyle risk factor modification strategy, including dietary and exercise advice, advice to quit smoking, and the prescription of open-label statins, ACE-I, and other antihypertensive medications where appropriate.

Group II: Randomized - Control Active Control 1 Intervention

The control will consist of usual clinical care, which may include a referral to a cardiologist or internist, or the use of treatments included in the intervention as clinically indicated, if part of the treating physician's standard practice.

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Canadian Cancer Society (CCS)

Collaborator

Trials

84

Recruited

42,100+

Prostate Cancer Canada

Collaborator

Trials

10

Recruited

7,500+

Published Research Related to This Trial

Cardiovascular disease (CVD) and aggressive prostate cancer share many risk factors, such as obesity, unhealthy diets, and lack of physical activity, suggesting that preventive measures for CVD may also help reduce prostate cancer risk.

Certain dietary supplements may increase prostate cancer risk, but safe and effective options like statins, aspirin, and metformin (collectively referred to as S.A.M.) could potentially lower this risk in healthy men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods. Moyad, MA.[2018]

Men with prostate cancer (PCa) who received first-line palliative treatment had significantly higher risks of ischemic stroke (IS) and heart failure (HF), with hazard ratios of 2.09 and 2.05, respectively, compared to PCa-free men over an 18-year follow-up period.

The study found no increased risk of myocardial infarction (MI) in men treated for PCa compared to cancer-free controls, indicating that lifestyle and cardiovascular risk factors did not account for the increased risks associated with palliative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of cardiovascular events in men treated for prostate cancer compared with prostate cancer-free men. Moustsen, IR., Larsen, SB., Duun-Henriksen, AK., et al.[2021]

Abiraterone treatment in advanced prostate cancer patients significantly increases the risk of hypertension, with an overall incidence of 21.9% and a relative risk of 1.80 compared to controls, based on a meta-analysis of five studies involving 5445 patients.

The risk of hypertension is further influenced by the concurrent use of prednisone, with a higher incidence observed in patients taking 5 mg daily compared to those taking 5 mg twice daily (32.4% vs 16.5%), highlighting the need for careful monitoring and management of blood pressure during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of hypertension in cancer patients treated with abiraterone: a meta-analysis. Zhu, X., Wu, S.[2022]

Lifestyle factors after a prostate cancer diagnosis, such as smoking and obesity, are linked to increased risks of disease progression and mortality, highlighting the importance of lifestyle management post-diagnosis.

Engaging in vigorous physical activity, walking briskly, and consuming a diet rich in vegetables and healthy fats may lower the risk of prostate cancer progression and improve overall survival, suggesting that these behaviors should be prioritized in patient counseling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What should we tell prostate cancer patients about (secondary) prevention? Chan, JM., Van Blarigan, EL., Kenfield, SA.[2023]

Recent studies suggest that maintaining heart health through diet and lifestyle can significantly reduce the risk of aggressive prostate cancer, highlighting the connection between cardiovascular health and prostate health.

While dietary supplements for prostate cancer prevention should be approached cautiously due to potential risks, heart-healthy medications like statins and aspirin show promise and warrant further research for their role in prostate cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing Lethal Prostate Cancer with Diet, Supplements, and Rx: Heart Healthy Continues to Be Prostate Healthy and "First Do No Harm" Part I. Moyad, MA.[2018]

A case study of a 72-year-old man revealed that Enzalutamide, an anti-androgen therapy for advanced prostate cancer, may cause systolic congestive heart failure, which improved after discontinuation of the drug.

While Enzalutamide is generally considered to have a safer cardiovascular profile than Abiraterone, this novel finding suggests the need for further research into its safety, particularly regarding cardiovascular risks associated with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide induced non-ischemic cardiomyopathy. A case report and review of literature on anti-androgen therapy-related cardiovascular events. Kumar, A., Reddy, A., Sekar, A.[2023]

Abiraterone treatment in advanced prostate cancer patients significantly increases the risk of hypertension, with an overall incidence of 21.9% and a relative risk of 1.80 compared to controls, based on a meta-analysis of five studies involving 5445 patients.

The risk of hypertension is further influenced by the concurrent use of prednisone, with a higher incidence observed in patients taking 5 mg daily compared to those taking 5 mg twice daily (32.4% vs 16.5%), highlighting the need for careful monitoring and management of blood pressure during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of hypertension in Cancer patients treated with Abiraterone: a meta-analysis. Zhu, X., Wu, S.[2022]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

Incorporating multiple moderate lifestyle changes can significantly reduce the risk of prostate cancer and all-cause mortality, as shown by clinical trials, emphasizing that overall effort is more impactful than focusing on individual changes.

Despite the simplicity of these lifestyle recommendations, adherence is low among men, with less than 5% managing to follow multiple healthy behaviors simultaneously, highlighting the need for better motivation and support from healthcare professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lifestyle recommendations to prevent prostate cancer, part II: time to redirect our attention? Moyad, MA., Carroll, PR.[2007]

Androgen receptor inhibitors like enzalutamide, apalutamide, and darolutamide may offer a safer treatment option for men with non-metastatic castration-resistant prostate cancer (nmCRPC) as they are associated with increased metastasis-free survival and potentially lower cardiovascular (CV) risks compared to traditional therapies like gonadotropic releasing hormone agonists.

It is crucial for healthcare providers to consider the cardiovascular health of patients with metastatic castration-resistant prostate cancer (mCRPC) when selecting treatments, as long-term androgen deprivation can increase CV disease risk, and drug interactions with other medications must also be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen receptor inhibitor treatments: Cardiovascular adverse events and comorbidity considerations in patients with non-metastatic prostate cancer. Morgans, AK., Shore, N., Cope, D., et al.[2021]

The Prostate 8-II trial is a 4-arm randomized controlled trial involving 200 men with prostate cancer, aiming to assess the effects of exercise and diet interventions on cancer recurrence and patient quality of life over a 24-month period after radical prostatectomy.

Participants are assigned to one of four groups (exercise-only, diet-only, exercise + diet, or usual care) and will receive various resources and support to help achieve their health goals, with the primary focus on measuring biochemical recurrence and secondary outcomes related to tumor biomarkers and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol for a 4-arm randomized controlled trial testing remotely delivered exercise-only, diet-only, and exercise + diet interventions among men with prostate cancer treated with radical prostatectomy (Prostate 8-II). Van Blarigan, EL., Chan, JM., Sanchez, A., et al.[2023]

The web-based intervention RiseTx successfully reduced sedentary time by an average of 455.4 weekly minutes and increased moderate-to-vigorous physical activity by 44.1 weekly minutes among 46 prostate cancer survivors over a 12-week period.

Participants reported high satisfaction with the intervention, indicating its feasibility; however, additional strategies may be necessary to maintain these behavior changes in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RiseTx: testing the feasibility of a web application for reducing sedentary behavior among prostate cancer survivors receiving androgen deprivation therapy. Trinh, L., Arbour-Nicitopoulos, KP., Sabiston, CM., et al.[2018]

Recent studies suggest that maintaining heart health is crucial for preventing aggressive prostate cancer, with evidence showing that a heart-healthy lifestyle can also reduce the risk of prostate cancer.

Dietary adherence to healthy foods is linked to lower risks of cardiovascular disease and potentially aggressive prostate cancer, while caution is advised regarding the use of dietary supplements, as they may not always be beneficial and could even increase cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing Lethal Prostate Cancer with Diet, Supplements, and Rx: Heart Healthy Continues to Be Prostate Healthy and "First Do No Harm" Part II. Moyad, MA.[2020]

Prostate cancer screening is controversial and currently not recommended as a systematic program, highlighting the importance of prevention strategies to reduce incidence and mortality.

Pharmaco-prevention options include drugs like 5-alpha-reductase inhibitors and statins, while diet-based prevention emphasizes the potential of natural foods and nutrients, though compliance remains a critical challenge for effective prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmaco and diet based prostate cancer prevention]. Eisinger, F., Cancel-Tassin, G., Azzouzi, AR., et al.[2013]

The Community of Wellness is a Web-based intervention designed to support prostate cancer survivors in improving their physical activity and dietary habits, with a randomized controlled trial currently enrolling 200 participants to assess its feasibility and acceptability.

Preliminary results will help determine the most effective level of online support needed to promote health behavior changes in men with prostate cancer, potentially informing future scalable health interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Increasing Levels of Web-Based Behavioral Support on Changes in Physical Activity, Diet, and Symptoms in Men With Prostate Cancer: Protocol for a Randomized Controlled Trial. Winters-Stone, KM., Kenfield, SA., Van Blarigan, EL., et al.[2020]

Citations

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Role of antihypertensive medicines in prostate cancer Thirteen studies reported reduced or no associated risk, improved prognosis, and survival with the use of RAS inhibitors. Studies on CCBs showed ...

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Effects of angiotensin-converting enzyme (ACE) inhibitors ... Conclusions: ACE inhibitors may increase the rates of PC-specific mortality in men receiving primary RT for PC. However these results need to be ...

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Use of angiotensin converting enzyme inhibitors is ... Use of angiotensin converting enzyme inhibitors is associated with reduced risk of late bladder toxicity following radiotherapy for prostate cancer.

5. ahajournals.org ahajournals.org/doi/10.1161/HYPERTENSIONAHA.120.16667

Comparative First-Line Effectiveness and Safety of ACE ... We compared the real-world effectiveness and safety of ACE inhibitors versus ARBs in the first-line treatment of hypertension.

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Angiotensin-converting enzyme (ACE) inhibitors Side effects. Possible side effects of ACE inhibitors are: Dry cough. Too much potassium in the blood. Extreme tiredness or dizziness from blood pressure ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK430896/

ACE Inhibitors - StatPearls - NCBI Bookshelf - NIH ACE inhibitors are a class of medication used to treat and manage hypertension, a significant risk factor for coronary disease, heart failure, stroke.

8. hhs.texas.gov hhs.texas.gov/sites/default/files/documents/jan-2024-durb-agenda-item5f.pdf

Angiotensin Modulators: ACE Inhibitors and Renin ... Several ACE inhibitors including benazepril, enalapril, fosinopril, and lisinopril have been shown to be safe and effective in children ages six to 16 years.

9. my.clevelandclinic.org my.clevelandclinic.org/health/treatments/21934-ace-inhibitors

Angiotensin-Converting Enzyme (ACE) Inhibitors They work. Extensive scientific research has shown that ACE inhibitors are effective. · They're preventive. ACE inhibitors don't just treat existing conditions.