Apalutamide + Carotuximab for Prostate Cancer

Recruiting at 2 trial locations

Overseen By Clinical Trial Recruitment Navigator

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Edwin Posadas, MD

Must be taking: ARSI therapy

Must not be taking: Apalutamide, Carotuximab

Disqualifiers: Small cell prostate cancer, 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: Unknown

Duration: Until documented progression or death, up to 30 days of follow-up after end of treatment

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding carotuximab to apalutamide (a hormone therapy) improves outcomes for prostate cancer patients who have not responded well to previous treatments. Researchers aim to determine if the combination prevents cancer progression longer than apalutamide alone. They will also examine side effects and the number of patients who benefit from the new treatment mix. Men with prostate cancer resistant to hormone therapy and rising PSA levels might be suitable candidates, especially if they have tried other hormone treatments but not apalutamide.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have used apalutamide before and should not have active bleeding conditions or certain other medical conditions.

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

Previous studies have shown that apalutamide is safe and effective for treating prostate cancer. Patients report that it is easy to tolerate and helps maintain their quality of life. Only a small number of patients experienced serious issues, such as blood flow problems in the brain.

Regarding the combination of apalutamide and carotuximab, early findings suggest that this mix is also easy to tolerate. Initial trial data show no severe side effects, indicating no intense or dangerous reactions. Overall, existing research suggests both treatments are safe options. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Apalutamide and Carotuximab for prostate cancer because it introduces a novel approach to treatment. Most prostate cancer treatments, like hormone therapies or chemotherapy, focus on reducing androgen levels or directly targeting rapidly dividing cells. However, Carotuximab is an experimental drug that may enhance the effectiveness of Apalutamide by targeting specific cancer pathways, potentially improving outcomes for patients who no longer respond to standard therapies. This innovative combination could offer new hope for patients with advanced prostate cancer.

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

Research has shown that apalutamide, which participants in this trial may receive as monotherapy, effectively treats prostate cancer. Studies indicate that when combined with androgen deprivation therapy (ADT), it can lower the risk of death and increase survival rates. One study found that patients had a 23% lower risk of dying over two years compared to those on another treatment.

Another treatment arm in this trial involves the combination of apalutamide and carotuximab. Early results for this combination are encouraging, showing that the cancer does not worsen for over 13 months on average, a 45% improvement compared to standard hormone therapy. This suggests it could be more effective for patients with advanced prostate cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Edwin Posadas, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

Men with castration-resistant prostate cancer that's gotten worse despite ARSI therapy (excluding bicalutamide, nilutamide, flutamide) can join. They should have tried at most two other AR therapies but not apalutamide and must opt out of or be unfit for taxane therapy. Participants need to use contraception during and for three months after the trial.

Inclusion Criteria

My prostate cancer is resistant to hormone therapy and my PSA levels are increasing.

I have had 1 or 2 prior hormone therapies for cancer, but not apalutamide.

I cannot or choose not to undergo taxane therapy as advised by my doctor.

Exclusion Criteria

I am currently receiving treatment for another cancer.

I have been diagnosed with Osler-Weber-Rendu syndrome.

I have never been treated with carotuximab or any CD105 targeted antibody.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Initial safety assessment in the first 10 subjects to determine the safety of the combination therapy

4 weeks

Treatment

Participants receive apalutamide and apalutamide + carotuximab to compare progression free survival

Until documented progression or death, up to 30 days of follow-up after end of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Apalutamide
• Carotuximab

Trial Overview The study is testing if adding carotuximab to apalutamide improves survival without cancer progression in men whose prostate cancer has worsened on ARSI treatment. It starts with a safety check on the first 10 patients before moving into a larger Phase II trial.

How Is the Trial Designed?

Group I: Combination therapy (Apalutamide + Carotuximab) Experimental Treatment 2 Interventions

Group II: Apalutamide monotherapy Active Control 1 Intervention

After progression, subjects will crossover to combination therapy

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

Approved in United States as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

Edwin Posadas, MD

Lead Sponsor

Trials

4

Recruited

140+

Enviro Therapeutics, Inc.

Collaborator

Trials

2

Recruited

160+

Published Research Related to This Trial

In a phase III study (TITAN) involving men with metastatic castration-sensitive prostate cancer, adding apalutamide to androgen deprivation therapy significantly improved median radiographic progression-free survival and overall survival.

Apalutamide was found to maintain health-related quality of life and had a safety profile similar to that of placebo when combined with androgen deprivation therapy, expanding treatment options for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. Hoy, SM.[2021]

Apalutamide is an oral androgen receptor inhibitor that effectively blocks androgen effects, and it received its first global approval in February 2018 for treating non-metastatic castration-resistant prostate cancer (nmCRPC).

Currently, apalutamide is being tested in phase III trials for various prostate cancer stages, including metastatic castration-resistant prostate cancer and high-risk localized prostate cancer, indicating its potential for broader applications in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. Al-Salama, ZT.[2019]

In a study involving 1,052 patients with metastatic castration-sensitive prostate cancer, apalutamide combined with androgen deprivation therapy (ADT) led to significant improvements in prostate-specific antigen (PSA) decline compared to placebo, with 90% of patients achieving a PSA decline of at least 50%.

The study found that achieving a deep PSA decline (≥90% or to ≤0.2 ng/ml) within 3 months of treatment with apalutamide was strongly associated with better overall survival and progression-free survival, indicating that rapid PSA response can be a predictor of long-term treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer. Chowdhury, S., Bjartell, A., Agarwal, N., et al.[2023]

In the SPARTAN study, apalutamide significantly improved overall survival (OS) in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC), showing a 25% reduction in the risk of death compared to placebo after a median follow-up of 41 months.

Apalutamide also enhanced second progression-free survival (PFS2) by 45%, indicating its efficacy in delaying disease progression, with no new safety concerns reported during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Small, EJ., Saad, F., Chowdhury, S., et al.[2023]

Apalutamide, an androgen receptor inhibitor for high-risk non-metastatic castration-resistant prostate cancer, shows rapid absorption and a large distribution volume, indicating effective body-wide delivery after oral administration.

In a study involving 1092 subjects, the pharmacokinetics of apalutamide and its metabolite were characterized, revealing low inter-individual variability and no significant predictors affecting drug clearance, suggesting consistent dosing effects across different patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Apalutamide and its Active Metabolite N-Desmethyl-Apalutamide in Healthy and Castration-Resistant Prostate Cancer Subjects. Pérez-Ruixo, C., Pérez-Blanco, JS., Chien, C., et al.[2021]

In the SPARTAN trial, apalutamide significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer (nmCRPC) receiving androgen-deprivation therapy, demonstrating its efficacy as a treatment option.

Apalutamide was generally well tolerated, with fatigue being the most common side effect, indicating a favorable safety profile while maintaining health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. Al-Salama, ZT.[2020]

In the SPARTAN study involving 1207 patients with nonmetastatic castration-resistant prostate cancer, apalutamide significantly improved health-related quality of life (HRQoL) compared to placebo, with patients maintaining better scores over time.

Patients receiving apalutamide experienced minimal side effects and reported no worsening of fatigue, while those on placebo showed a decline in quality of life after about one year, highlighting the efficacy and tolerability of apalutamide in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. Oudard, S., Hadaschik, B., Saad, F., et al.[2022]

In a study involving 57 patients with metastatic castration-resistant prostate cancer (mCRPC), the combination of apalutamide with abiraterone acetate and prednisone was well tolerated and demonstrated significant antitumor activity, particularly in patients who had not previously been treated with androgen receptor inhibitors.

While apalutamide reduced the systemic exposure to prednisone by 61%, no significant adverse events related to mineralocorticoid excess were observed, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Antitumor Effect of Apalutamide with Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer: Phase Ib Study. Posadas, EM., Chi, KN., de Wit, R., et al.[2021]

Citations

1. nature.com nature.com/articles/s41391-024-00929-6

Survival outcomes of apalutamide as a starting treatment Starting treatment with APA + ADT was associated with a significantly reduced risk of death compared with ENZ + ADT (aHR, 95%CI) (0.66, 0.51– ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39613567/

Results from the Multicenter Real-world ARON-3 Study Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

3. urotoday.com urotoday.com/video-lectures/mhspc/video/mediaitem/4763-real-world-data-explores-benefits-of-apalutamide-in-metastatic-hormone-sensitive-prostate-cancer-benjamin-maughan.html

Real-World Data Explores Benefits of Apalutamide in ... All doublet combinations showed superior outcomes compared to ADT monotherapy, with apalutamide demonstrating numerically superior results. Dr.

4. jnj.com jnj.com/media-center/press-releases/erleada-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer

ERLEADA® (apalutamide) demonstrates statistically ... Largest head-to-head real-world study in mCSPC demonstrated that ERLEADA® reduced risk of death by 23 percent at 24 months compared to ...

5. erleadahcp.com erleadahcp.com/efficacy/

Efficacy | ERLEADA® (apalutamide) HCP Median follow-up time was 44.0 months. 1. The survival rate at 48 months was 65.1% for ERLEADA ® + ADT patients vs 51.8% for placebo + ADT patients.

6. erleadahcp.com erleadahcp.com/patient-reported-outcomes/

PATIENT-REPORTED OUTCOMES FOR HRQoL 1-6 Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA® and 2 patients (0.2%) treated with placebo died from a cerebrovascular event.

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1903307

Apalutamide for Metastatic, Castration-Sensitive Prostate ... In our trial, initial therapy with apalutamide in patients with metastatic, castration-sensitive prostate cancer led to improved clinical outcomes. The intent ...

8. jnj.com jnj.com/innovativemedicine/us/news-center/oncology/erleada-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer

ERLEADA® (apalutamide) demonstrates statistically ... Largest head-to-head real-world study in mCSPC demonstrated that ERLEADA® reduced risk of death by 23 percent at 24 months compared to enzalutamide.

9. nature.com nature.com/articles/s41416-023-02492-8

Apalutamide efficacy, safety and wellbeing in older patients ... Conclusions. Apalutamide plus ADT was an effective and well-tolerated option maintaining HRQoL in patients with mCSPC and nmCRPC regardless of ...