Sunitinib + Hormone Therapy for Prostate Cancer

Age: Any Age

Sex: Male

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Hormonal therapy

Must not be taking: Ketoconazole, Chemotherapy, Experimental agents, Coumadin

Disqualifiers: Metastatic disease, Severe hypertension, 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: 9

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding sunitinib malate to standard hormone therapy (LHRH agonist) can shrink or control prostate cancer tumors before surgery. It targets men with removable prostate cancer and certain high-risk features, such as specific tumor size or aggressive cancer type. Candidates include those who have already received some hormone therapy and are planning for surgery. The goal is to determine if this combination treatment is more effective than hormone therapy alone. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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. However, if you are on ketoconazole or therapeutic doses of coumadin, you may need to stop or adjust these medications. It's best to discuss your current medications with the trial team.

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

Research has shown that sunitinib malate, also known as Sutent, is generally safe for men with prostate cancer. One study found it to be safe and manageable, with patients experiencing side effects similar to those in other studies. Importantly, the FDA has already approved sunitinib for other conditions, suggesting its safety.

LHRH agonists, which help lower certain hormone levels, have demonstrated long-term benefits for prostate cancer patients. However, some studies suggest a higher risk of heart-related issues with these treatments. Discussing this with a doctor is important to understand personal risks.

Overall, both treatments have been used in other situations and have a known safety record, but individual experiences may vary. Consulting a healthcare provider about any concerns is always best. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about the combination of Sunitinib Malate with hormone therapy for prostate cancer because it offers a novel approach to treatment. Unlike the standard hormone therapies that primarily focus on reducing testosterone levels, Sunitinib Malate is a tyrosine kinase inhibitor that targets blood vessel growth in tumors, potentially enhancing the effectiveness of hormone ablation. This dual-action approach could lead to better control of the cancer and improve surgical outcomes when followed by prostatectomy. Additionally, the treatment is administered over a short period, potentially allowing for quicker patient recovery and reduced side effects compared to prolonged hormone therapy alone.

What evidence suggests that the combination of sunitinib and hormone therapy might be an effective treatment for prostate cancer?

Research shows that sunitinib malate, a treatment in this trial, can slow tumor growth by blocking the pathways cancer cells use to grow blood vessels. In some studies, sunitinib alone led to tumor shrinkage in up to 59% of cases. LHRH agonists, another treatment option in this trial, are used in hormone therapy and have demonstrated long-term survival benefits for prostate cancer patients by reducing testosterone levels, which cancer cells need to grow. This trial combines these treatments to control tumors as much as possible before surgery. Early findings suggest that combining sunitinib with hormone therapy might enhance these effects, but further research is needed to confirm this. ^{1 2 4 6 7}

Who Is on the Research Team?

Amado Zurita, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for men with confirmed adenocarcinoma of the prostate that's considered removable by surgery. They must be at low risk for anesthesia during prostate removal, intend to have this surgery after therapy, and meet specific cancer severity criteria (like Gleason score 8-10). Participants need normal organ function and can't have had certain treatments or conditions like metastatic disease, recent heart issues, uncontrolled hypertension or diabetes.

Inclusion Criteria

My prostate cancer is confirmed and considered removable by surgery.

Patients must sign the current IRB approved informed consent indicating that they are aware of the investigational nature of this study, in keeping with the policies of the institution.

I have had hormonal therapy for up to 2 months.

Exclusion Criteria

My prostate cancer is not small cell or sarcomatoid type.

I have been treated with ketoconazole for hormone therapy.

I do not have an infection that could worsen with the study treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive sunitinib malate and hormonal ablation therapy for up to 3 cycles, each lasting 30 days

12 weeks

4 visits (in-person) per cycle

Surgery

Participants undergo prostatectomy 1-2 weeks after completing treatment

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including PSA tests and physical exams

3 months

3 visits (in-person)

Long-term Follow-up

Participants have PSA tests every 3 months for the first year, then every 6 months for the second year

2 years

What Are the Treatments Tested in This Trial?

Interventions

• LHRH Agonist
• Radical Prostatectomy
• Sunitinib Malate

Trial Overview The study tests if adding Sunitinib Malate to hormone-based castration before removing the prostate helps shrink/control the tumor. It involves a drug called Sunitinib Malate combined with hormonal therapy prior to radical prostatectomy—a surgical procedure to remove the prostate gland.

How Is the Trial Designed?

Group I: Sunitinib + Hormonal Ablation Before Prostatectomy Experimental Treatment 3 Interventions

Sunitinib Malate 25 to 37.5 mg/day once daily for 30 days (= 1 cycle), up to 3 cycles. LHRH Agonist intramuscular injection either monthly for 3 months or in a single 3-month dose. Radical prostatectomy after completion of Sunitinib and LHRH agonist.

LHRH Agonist is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as LHRH agonist for:

• Prostate cancer
• Breast cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in United States as LHRH agonist for:

• Prostate cancer
• Breast cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in Canada as LHRH agonist for:

• Prostate cancer
• Breast cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in Japan as LHRH agonist for:

• Prostate cancer
• Breast cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a phase II study involving 62 advanced prostate cancer patients, high-dose estetrol (HDE4) combined with androgen deprivation therapy (ADT) significantly reduced the frequency and severity of hot flushes, with only 13.5% of patients experiencing weekly hot flushes compared to 60% in the placebo group.

HDE4 treatment also led to a more rapid and profound suppression of total and free testosterone, prostate-specific antigen (PSA), and follicle-stimulating hormone (FSH), while showing no serious cardiovascular adverse events, indicating its potential for enhanced disease control and safety in ADT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estetrol Cotreatment of Androgen Deprivation Therapy in Infiltrating or Metastatic, Castration-sensitive Prostate Cancer: A Randomized, Double-blind, Phase II Trial (PCombi). Coelingh Bennink, HJT., van Moorselaar, JA., Crawford, ED., et al.[2022]

GnRH antagonists provide faster suppression of hormones like luteinising hormone and testosterone compared to GnRH agonists, leading to improved disease control in advanced prostate cancer.

Patients receiving GnRH antagonists have a significantly lower risk of cardiac events within one year of treatment initiation, making them a safer option for men with pre-existing cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK. Rosario, DJ., Davey, P., Green, J., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11667785/

Luteinizing hormone-releasing hormone receptor agonists ... LHRH-R agonists and antagonists, particularly goserelin, have demonstrated long-term survival benefits in patients with localized and locally advanced prostate ...

2. journals.lww.com journals.lww.com/indianjcancer/fulltext/2022/59001/gonadotropin_releasing_hormone_agonists_in.12.aspx

Gonadotropin-releasing hormone agonists in prostate cancer Table 1 shows that the PSA level of ≤4 ng/mL was achieved by 78.4% to 90% patients receiving GnRH-A[3233373941]; the highest percentage of the patients achieved ...

3. auajournals.org auajournals.org/doi/10.1097/JU.0000000000003721

Cardiovascular Risk in Prostate Cancer Patients Using ... Epidemiological data suggest an increased risk of CV events following initiation of both LHRH agonist and GnRH antagonist therapies, but these ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666087323001710

Cardiovascular Effects of GnRH Antagonists Compared ... The available data suggest that GnRH antagonists are associated with fewer cardiovascular events, and possibly mortality, compared with GnRH agonists.

5. openurologyandnephrologyjournal.com openurologyandnephrologyjournal.com/VOLUME/17/ELOCATOR/e1874303X237036/FULLTEXT/

6-month Formulations of Androgen Deprivation Therapy for ... A recent analysis found a high non-adherence rate of 84% for LHRH agonist injections based on dosing schedules used in pivotal trials. Method:.

6. jacc.org jacc.org/doi/10.1016/j.jaccao.2023.05.011

Cardiovascular Effects of GnRH Antagonists Compared ... Cardiovascular safety of degarelix versus leuprolide in patients with prostate cancer: the primary results of the PRONOUNCE randomized trial.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1078143924010585

Risk of cardiovascular disease following degarelix versus ... Degarelix demonstrates a lower incidence of major adverse cardiovascular events compared to GnRH agonists, suggesting a potential cardiovascular safety ...