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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether antiandrogen therapy is more effective with or without the drug axitinib before surgery in treating prostate cancer that may have spread to the lymph nodes. Antiandrogen therapy, also known as hormone therapy or androgen deprivation therapy, reduces hormones that promote prostate cancer growth, while axitinib may inhibit tumor cell growth. The trial seeks men with prostate cancer that could potentially be surgically removed after treatment. Participants should have prostate cancer suspected to have spread to the lymph nodes and be prepared for surgery following the therapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in prostate cancer treatment.

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.

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

Research has shown that antiandrogen therapy, used to lower hormones that promote prostate cancer growth, is generally well-tolerated. Many men with prostate cancer have safely used these treatments over time.

However, combining antiandrogen therapy with axitinib changes the situation. Axitinib may help stop tumors from growing by blocking certain enzymes. Some studies have reported positive results with this combination, but combining treatments can sometimes lead to more side effects.

Unfortunately, detailed information about specific side effects from these studies is limited. As this trial remains in the early stages, researchers are still studying the treatment's safety in humans. Participants should be aware of potential risks and discuss these with their healthcare provider before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they explore the potential of combining antiandrogen therapy with axitinib, a drug typically used for kidney cancer. Unlike the standard care, which often involves just hormone therapy and surgery, adding axitinib aims to block blood vessel growth that tumors need to thrive. This combination could potentially improve outcomes by targeting cancer from multiple angles, offering a new approach that might enhance the effectiveness of existing therapies.

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

This trial will compare the effects of antiandrogen therapy alone to the combination of antiandrogen therapy and axitinib for prostate cancer. Research has shown that adding axitinib to antiandrogen therapy might benefit prostate cancer patients more than antiandrogen therapy alone. One study found that 36.8% of patients receiving both treatments responded positively, compared to 19% who received only antiandrogen therapy. This suggests that axitinib could enhance the effectiveness of antiandrogen therapy by blocking certain enzymes that promote cancer cell growth. Antiandrogen therapy alone works by lowering hormones that can cause prostate cancer cells to grow. These findings suggest that the combination might be more effective in controlling cancer spread before surgery. ^{1 2 3 5 6}

Who Is on the Research Team?

Amado J Zurita Saavedra

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2588931125001063

Randomized Phase 2 Trial of Presurgical Androgen ... In the node-positive group of 55 patients, the success rate was 36.8% (95% credible interval [CrI] 22.5–52.5%) for axitinib + ADT and 19.0% (95% CrI 5.7–37.9%) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01409200

Antiandrogen Therapy With or Without Axitinib Before ... 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.

3. withpower.com withpower.com/trial/phase-3-adenocarcinoma-2-2012-fcf29

Antiandrogen Therapy +/− Axitinib for Prostate Cancer This randomized phase IIA trial studies how well antiandrogen therapy works with or without axitinib before surgery in treating patients with previously ...

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1324181/full

Comparative effectiveness of multiple androgen receptor ... Abiraterone, enzalutamide, and apalutamide were found to significantly reduce and stabilize PSA levels in mHSPC patients more quickly and thoroughly than ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.5078

Randomized phase II trial of presurgical androgen ... Conclusions: 1 year after RP, ADT+Axi resulted in proportionally greater number of LN+ PCa pts off treatment and progression free than ADT alone ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6896415/

Combined Modality Therapies for High-Risk Prostate Cancer Long-term follow-up of a randomized trial of radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA. (2015) 314:1291–3 ...