Antiandrogen Therapy +/− Axitinib for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Antiandrogens

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Small cell histology, Extranodal metastasis, Gastrointestinal abnormalities, Heart failure, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 4 months

73 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you cannot take certain drugs that affect liver enzymes (like some antibiotics and antifungals) during the study. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the treatment Antiandrogen Therapy, Hormone therapy, Androgen deprivation therapy, Axitinib, Inlyta for prostate cancer?

Androgen deprivation therapy (ADT) is a well-established treatment for advanced prostate cancer, effectively reducing symptoms and improving survival when combined with radiation for locally advanced cases. However, there is no evidence supporting the use of nonsteroidal antiandrogens alone or in combination for locally advanced prostate cancer. ^{1 2 3 4 5}

Is antiandrogen therapy safe for humans?

Antiandrogen therapy, often used for prostate cancer, can have side effects that affect quality of life, including impacts on physical function and health-related quality of life. It is associated with adverse effects on cardiometabolic and musculoskeletal health, and exercise may help manage these effects. ^{6 7 8 9 10}

How is the drug combination of Antiandrogen Therapy and Axitinib unique for treating prostate cancer?

This treatment is unique because it combines antiandrogen therapy, which reduces male hormones that fuel prostate cancer, with Axitinib, a drug typically used for kidney cancer that blocks blood vessel growth in tumors. This combination aims to enhance the effectiveness of hormone therapy by also targeting the tumor's blood supply. ^{1 3 8 11 12}

What is the purpose of this trial?

This randomized phase IIA trial studies how well antiandrogen therapy works with or without axitinib before surgery in treating patients with previously untreated prostate cancer that is known or suspected to have spread to lymph nodes. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as antiandrogen therapy may lessen the amount of androgen made by the body. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if antiandrogen therapy is more effective with or without axitinib before surgery in treating patients with prostate cancer.

Research Team

Amado J Zurita Saavedra

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Men with untreated prostate cancer that has spread to lymph nodes may join this trial. They must be fit for surgery, have a good performance status (ECOG 2 or better), and agree to use contraception. Excluded are those who've had prior chemotherapy, more than 8 weeks of hormone therapy, certain other health issues, or are on drugs affecting the study medication.

Inclusion Criteria

I have consulted with both a surgeon and a medical oncologist before agreeing to participate.

Meeting specified laboratory criteria for ANC, platelet count, total bilirubin, AST/ALT, serum creatinine, and urinary protein

I can do most of my daily activities but not heavy physical work.

Exclusion Criteria

I do not have stomach or digestion problems that affect how my body uses medicine.

Overt psychosis, mental disability, incompetence to give informed consent, or history of non-compliance

Planned participation in any other experimental drug study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants receive antiandrogen therapy per standard care for 8 weeks

8 weeks

Treatment

Participants receive antiandrogen therapy with or without axitinib for 4 months, followed by radical prostatectomy and pelvic lymph node dissection

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

1 and 3 months, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then yearly

Treatment Details

Interventions

• Antiandrogen Therapy
• Axitinib

Trial Overview The trial is testing if antiandrogen therapy alone or combined with Axitinib is more effective before surgery in patients with prostate cancer that has possibly spread to lymph nodes. It's unknown whether adding Axitinib improves outcomes.

Participant Groups

Group I: Arm I (antiandrogen therapy, axitinib, surgery) Experimental Treatment 4 Interventions

Patients receive antiandrogen therapy per standard care and axitinib PO BID for 4 months. Patients then undergo radical prostatectomy and pelvic lymph node dissection.

Group II: Arm II (antiandrogen therapy, surgery) Active Control 3 Interventions

Patients receive antiandrogen therapy per standard care for 4 months and then undergo radical prostatectomy and pelvic lymph node dissection.

Antiandrogen Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Antiandrogen Therapy for:

• Prostate cancer

Approved in European Union as Antiandrogen Therapy for:

• Prostate cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Androgen deprivation therapy (ADT) is effective for managing symptoms of prostate cancer but can lead to significant side effects that worsen over time, and it does not improve survival in men with localized disease.

Neoadjuvant ADT combined with external beam radiation has been shown to enhance survival in men with locally advanced prostate cancer, while immediate adjuvant ADT does not provide benefits for most men after radical prostatectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The timing and extent of androgen deprivation therapy for prostate cancer: weighing the clinical evidence. Ginzburg, S., Albertsen, PC.[2019]

Androgen deprivation therapy (ADT) significantly improves lower urinary tract symptoms (LUTS) and quality of life (QoL) in patients with advanced prostate cancer, as shown by a study of 65 patients over 12 months, with notable reductions in mean IPSS scores and improvements in urodynamic parameters.

Despite the overall benefits of ADT, a subset of patients (approximately 12.3%) continued to experience persistent LUTS and required catheterization, indicating that not all patients respond equally to this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower urinary tract symptoms in patients with advanced prostate cancer: What are the outcomes of androgen deprivation therapy? Akpayak, IC., Shuaibu, SI., Ofoha, CG., et al.[2022]

In a pooled analysis of 920 prostate cancer patients, triptorelin sustained-release formulations effectively suppressed serum testosterone levels to below 20 ng/dl in 79% to 93% of patients over various treatment durations (1 to 12 months).

The study suggests that achieving very low testosterone levels may provide additional clinical benefits, highlighting the importance of routine testosterone monitoring in patients undergoing androgen deprivation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Testosterone Suppression with Sustained-Release Triptorelin in Advanced Prostate Cancer. Breul, J., Lundström, E., Purcea, D., et al.[2018]

Androgen deprivation therapy (ADT) is crucial for treating prostate cancer, particularly in high-risk or metastatic cases, but its benefits are not well-established for all patients due to significant side effects.

ADT can lead to severe hypogonadism and various adverse effects, especially impacting cardiometabolic and musculoskeletal health, highlighting the need for further research on its risk-benefit ratio.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgens and prostate cancer; pathogenesis and deprivation therapy. Grossmann, M., Cheung, AS., Zajac, JD.[2013]

Exercise is strongly supported as an effective strategy to manage several adverse effects of androgen deprivation therapy (ADT) in prostate cancer patients, including loss of muscle mass, fatigue, and declining physical function.

In addition to physical benefits, exercise may also improve mental health outcomes such as depression and anxiety, suggesting it plays a crucial role in enhancing overall quality of life and survivorship for men undergoing ADT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of exercise in the management of adverse effects of androgen deprivation therapy for prostate cancer: a rapid review. Edmunds, K., Tuffaha, H., Scuffham, P., et al.[2021]

In a study involving 1974 men with high-risk non-metastatic prostate cancer, combination therapy with abiraterone acetate and prednisolone significantly improved metastasis-free survival compared to androgen-deprivation therapy (ADT) alone, with a hazard ratio of 0.53, indicating a 47% reduction in the risk of metastasis.

The combination therapy also showed significant improvements in overall survival, prostate cancer-specific survival, and biochemical failure-free survival, although it was associated with a higher incidence of grade 3 or higher adverse events, such as hypertension and liver enzyme elevation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

References

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

The timing and extent of androgen deprivation therapy for prostate cancer: weighing the clinical evidence. [2019]

2. Nigeria pubmed.ncbi.nlm.nih.gov

Lower urinary tract symptoms in patients with advanced prostate cancer: What are the outcomes of androgen deprivation therapy? [2022]

3. Poland pubmed.ncbi.nlm.nih.gov

Evidence-based recommendations on androgen deprivation therapy for localized and advanced prostate cancer. [2020]

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

Efficacy of Testosterone Suppression with Sustained-Release Triptorelin in Advanced Prostate Cancer. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Clinical outcomes of androgen deprivation as the sole therapy for localized and locally advanced prostate cancer. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Body composition, physical function and quality of life in healthy men and across different stages of prostate cancer. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study. [2022]

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

Safety of antiandrogen therapy for treating prostate cancer. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Androgens and prostate cancer; pathogenesis and deprivation therapy. [2013]

10. Germany pubmed.ncbi.nlm.nih.gov

The role of exercise in the management of adverse effects of androgen deprivation therapy for prostate cancer: a rapid review. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. [2023]

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

Bicalutamide dosages used in the treatment of prostate cancer. [2019]