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

64 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical research study is to learn if the addition of sunitinib malate (SU011248) to hormone based castration is an effective treatment for shrinking or controlling the tumor before having the prostate removed.

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.

What data supports the effectiveness of the drug Sunitinib + Hormone Therapy for Prostate Cancer?

Research shows that LHRH agonists, which are part of the hormone therapy, are effective in treating advanced prostate cancer by reducing testosterone levels, which helps control cancer growth. This effectiveness has been demonstrated in several clinical trials, making them a reasonable treatment option for metastatic prostate cancer. ^{1 2 3 4 5}

Is the combination of Sunitinib and hormone therapy safe for prostate cancer treatment?

Hormone therapies like LHRH agonists, used in prostate cancer treatment, have been associated with cardiovascular risks, but they are generally considered safe when used alone. Sunitinib, used in other conditions, has known side effects like fatigue and high blood pressure, but specific safety data for its combination with hormone therapy in prostate cancer is not detailed in the provided research. ^{1 5 6 7 8}

How is the drug Sunitinib + Hormone Therapy for Prostate Cancer different from other treatments?

This treatment combines Sunitinib, a drug that targets cancer cell growth, with hormone therapy using LHRH agonists, which reduce testosterone levels. This combination is unique because it not only suppresses hormones that fuel prostate cancer but also directly targets cancer cells, potentially offering a more comprehensive approach than hormone therapy alone. ^{1 2 4 6 9}

Research Team

Amado Zurita, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. Netherlands 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). [2022]

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

Early development of castrate resistance varies with different dosing regimens of luteinizing hormone releasing hormone agonist in primary hormonal therapy for prostate cancer. [2013]

3. Germany 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. [2022]

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

Abarelix Depot, a GnRH antagonist, v LHRH superagonists in prostate cancer: differential effects on follicle-stimulating hormone. Abarelix Depot study group. [2010]

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

Luteinizing hormone-releasing hormone (LHRH) agonists for treatment of advanced prostatic carcinoma. [2019]

6. Japan pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety of 1- and 3-month luteinizing hormone-releasing hormone agonist depots as initial therapies for prostate cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Abarelix for injectable suspension: first-in-class gonadotropin-releasing hormone antagonist for prostate cancer. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Cardiovascular adverse events-related to GnRH agonists and GnRH antagonists: analysis of real-life data from Eudra-Vigilance and Food and Drug Administration databases entries. [2023]

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

Traditional approaches to androgen deprivation therapy. [2013]