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

Trial Summary

What is the purpose of this trial?

This is an open-label, multi-site study of apalutamide with carotuximab in patients who have progressed on androgen receptor signaling inhibitor (ARSI) therapy. This study will begin with a safety assessment in the first 10 subjects (part 1: Safety Lead-in). If the combination is deemed safe, the trial will proceed to the Phase II stage. The purpose of this study is to compare progression free survival (PFS) between patients receiving apalutamide and apalutamide + carotuximab using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Prostate Cancer Working Group 3. The secondary objectives are to describe adverse events related to the intervention, overall response rate (ORR), proportion of patients resistant to apalutamide that benefit from the addition of carotuximab, and to determine the ORR, radiographic PFS, and biochemical PFS in the overall population.

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.

What data supports the effectiveness of the drug combination Apalutamide and Carotuximab for prostate cancer?

Research shows that Apalutamide, when used with androgen deprivation therapy, improves survival and delays disease progression in prostate cancer patients. However, there is no specific data on the effectiveness of Carotuximab in this combination for prostate cancer. ^{1 2 3 4 5}

Is the combination of Apalutamide and Carotuximab safe for humans?

Apalutamide, used for prostate cancer, has been studied and is generally considered safe when used with other treatments like androgen deprivation therapy, without major safety differences compared to placebo. However, there is no specific safety data available for the combination of Apalutamide and Carotuximab. ^{1 2 5 6 7}

What makes the drug Apalutamide unique for prostate cancer treatment?

Apalutamide is a next-generation oral drug that blocks the effects of androgens (male hormones) by directly binding to the androgen receptor, making it effective for treating both non-metastatic and metastatic prostate cancer. It is unique because it can be used in combination with other therapies, like androgen deprivation therapy, to improve survival and delay disease progression while maintaining quality of life. ^{1 5 6 7 8}

Research Team

Edwin Posadas, MD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. Netherlands 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. [2022]

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. [2023]

5. United States 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. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Apalutamide and its Active Metabolite N-Desmethyl-Apalutamide in Healthy and Castration-Resistant Prostate Cancer Subjects. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

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