Semaglutide for Prostate Cancer

(GAINPCCONTROL Trial)

Overseen By Steven Agapay, BSc

Age: 18+

Sex: Male

Trial Phase: Phase 4

Sponsor: Hamilton Health Sciences Corporation

Must be taking: Androgen deprivation therapy

Must not be taking: GLP-1 receptor agonists

Disqualifiers: Type 1 diabetes, Pancreatitis, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 6 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether semaglutide, a medication typically used for weight management, can help control prostate cancer in men already receiving hormone therapy. The study aims to determine if this treatment can improve outcomes for those undergoing androgen deprivation therapy, a common prostate cancer treatment. Suitable candidates include men with prostate cancer who are on or planning to start hormone therapy and have a higher body weight or conditions such as high blood pressure, type 2 diabetes, or sleep apnea. As a Phase 4 trial, this research explores how an FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking a GLP-1 RA (a type of medication for diabetes).

What is the safety track record for this treatment?

A previous study found that semaglutide did not increase the risk of cancer, including prostate cancer, meaning it was not linked to causing cancer in users. Research has shown that semaglutide is generally well-tolerated, with most people not experiencing serious side effects. However, some individuals might encounter minor issues like nausea or slight discomfort.

Since semaglutide is in a Phase 4 trial, it has already received approval for other conditions, such as diabetes. Its use for these conditions suggests it is considered safe for humans, with any serious side effects being rare or manageable. Participants should discuss any concerns or questions with a doctor or the trial team. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for prostate cancer, which often involve hormone therapy or chemotherapy, semaglutide is unique because it is a GLP-1 receptor agonist. This means it works by mimicking a hormone that regulates insulin and appetite, which is quite different from how conventional treatments target cancer cells directly. Researchers are excited about semaglutide because it offers a novel approach to potentially manage prostate cancer by impacting metabolic pathways, which might lead to fewer side effects and improved quality of life for patients. Additionally, this treatment is administered as a once-weekly subcutaneous injection, which could be more convenient and less invasive compared to more frequent dosing or intravenous therapies.

What is the effectiveness track record for semaglutide in treating prostate cancer?

Research has shown that semaglutide, a drug that mimics a hormone to lower blood sugar, may benefit prostate cancer treatment. Early studies demonstrated that semaglutide slowed cell growth and reduced energy production in prostate cancer cells. Additionally, some studies suggest that this type of drug can help inhibit prostate cancer. Evidence also indicates that these drugs might lower the overall risk of cancer, with semaglutide significantly reducing the risk for various conditions. This trial will investigate the effectiveness of semaglutide in managing prostate cancer, potentially in combination with androgen deprivation therapy. ^{2 4 6 7 8}

Who Is on the Research Team?

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

Principal Investigator

Population Health Research Institute and McMaster University

Jehonathan Pinthus, MD,FRCS(C),PhD

Principal Investigator

Juravinski Cancer Centre

Are You a Good Fit for This Trial?

Men with prostate cancer undergoing androgen deprivation therapy can join this trial. They must have a physician's diagnosis, be overweight (BMI ≥30 or ≥27 with certain conditions like hypertension), and not have type 1 diabetes, thyroid cancer history, pancreatitis, or multiple endocrine neoplasia type 2.

Inclusion Criteria

I have been diagnosed with pancreatic cancer by a doctor.

I am undergoing or will undergo hormone therapy for my cancer.

My BMI is high and I may have hypertension, diabetes, sleep apnea, or high cholesterol.

Exclusion Criteria

I have Type 1 diabetes.

I am currently taking a GLP-1 receptor agonist medication.

I am under 18 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive semaglutide with dose escalation over 6 months

6 months

Baseline visit, 1-month telephone follow-up, 3-month visit, 6-month close-out visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview The GAIN PC CONTROL study is testing the effects of Semaglutide Pen Injector on men with prostate cancer who are receiving hormone treatments to lower testosterone levels. The focus is on how this medication impacts their condition.

How Is the Trial Designed?

Group I: Semaglutide Experimental Treatment 1 Intervention

The semaglutide dose will be 0.25mg subcutaneously once weekly for weeks 1-4, then 0.5mg once weekly for weeks 5-8, then 1mg once weekly for weeks 9-12, then 1.7mg once weekly for weeks 13-16, and then 2.4mg for the remainder of the trial. Semaglutide dose may be decreased in the case of adverse events to the highest tolerated dose.

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Published Research Related to This Trial

In a study of 24 patients with primary prostate cancer, Ga-PSMA-11 PET/CT demonstrated a high detection rate of 95.8%, confirming its effectiveness in identifying cancerous lesions.

Dynamic PET/CT imaging showed that Ga-PSMA-11 accumulation in prostate cancer lesions increased over time, suggesting its potential for enhancing treatment strategies targeting PSMA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga-PSMA-11 Dynamic PET/CT Imaging in Primary Prostate Cancer. Sachpekidis, C., Kopka, K., Eder, M., et al.[2022]

A novel gastrin-releasing peptide receptor (GRPR) ligand, AMTG, shows promise for detecting and treating prostate cancer, especially in patients with PSMA-negative lesions, demonstrating high GRPR affinity and favorable biodistribution in preclinical studies.

In a proof-of-concept study, the 68Ga-labeled AMTG showed intense uptake in metastatic lesions in a patient with castration-resistant prostate cancer, indicating its potential for effective theranostic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Comparison of the 64Cu- and 68Ga-Labeled GRPR-Targeted Compounds RM2 and AMTG, as Well as First-in-Humans [68Ga]Ga-AMTG PET/CT. Koller, L., Joksch, M., Schwarzenböck, S., et al.[2023]

The ENZA-p trial is investigating the safety and efficacy of combining lutetium-177 (177 Lu)-PSMA-617 with enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC), aiming to improve prostate-specific antigen (PSA) progression-free survival (PFS) in high-risk patients.

This phase 2 trial will enroll 160 participants and assess various outcomes, including overall survival and quality of life, while also identifying potential biomarkers to personalize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901). Emmett, L., Subramaniam, S., Joshua, AM., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.182

GLP1R expression in prostate cancer patients and effects ... Semaglutide treatment in pre-clinical prostate cancer models resulted in decreased cell proliferation, decreased glycolytic function, and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12071316/

May Patients Receiving GLP-1 Agonists Be at Lower Risk of ... The results revealed that GLP-1 receptor agonists (particularly semaglutide) afforded a significant risk reduction encompassing 25 different ...

3. biomarkerres.biomedcentral.com biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00765-3

Glucagon-like peptide 1 receptor agonists and cancer risk Liraglutide has also been shown to significantly reduce the incidence of prostate cancer and improve survival outcomes in diabetic patients ...

4. journals.lww.com journals.lww.com/md-journal/fulltext/2024/10110/effect_of_glucagon_like_peptide_1_receptor.66.aspx

Effect of glucagon-like peptide-1 receptor agonists on... Some studies have shown that GLP-1RA has an inhibitory effect on prostate cancer, and its application will produce adverse effects associated with an increased ...

5. thelancet.com thelancet.com/journals/lanepe/article/PIIS2666-7762(25)00138-3/fulltext

Long-term cancer risk in users of GLP-1 agonists in Denmark Long-term sustained users of GLP-1RA had a small increased risk of cancer; potentially explained by a survival benefit.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11479428/

Effect of glucagon-like peptide-1 receptor agonists on prostate ... Several clinical studies have shown a reduced risk of prostate cancer with the use of GLP-1 receptor agonists (GLP-1RAs). In a nationwide cohort study by ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1871402123001303

Semaglutide and cancer: A systematic review and meta- ... Semaglutide use in RCTs and real-world studies was not associated with an increased risk of any types of cancer, and this conclusion is supported by a high ...

8. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.5_suppl.182

GLP1R expression in prostate cancer patients and effects ... Semaglutide treatment in pre-clinical prostate cancer models resulted in decreased cell proliferation, decreased glycolytic function, and ...