Apalutamide + Carotuximab for Prostate Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Edwin Posadas, MD

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Edwin Posadas, MD

Must be taking: ARSI therapy

Must not be taking: Apalutamide, Carotuximab

Disqualifiers: Small cell prostate cancer, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

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}

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.

Trial 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 (Hormone Therapy)
• Carotuximab (Monoclonal Antibodies)

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

City of Hope Duarte, CA

Huntsman Cancer Institute and Hospital Salt Lake City, UT

Cedars-Sinai Medical Center Los Angeles, CA

Who Is Running the Clinical Trial?

Edwin Posadas, MD Lead Sponsor

Enviro Therapeutics, Inc. Collaborator

References

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

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. [2021] Apalutamide (Erleada®) is an oral selective androgen receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. It is approved in the EU and the USA for the treatment of adult men with metastatic castration-sensitive prostate cancer (mCSPC). In a multinational, phase III study (TITAN) in this patient population, the addition of apalutamide (240 mg once daily) to androgen deprivation therapy (ADT) significantly improved median radiographic progression-free survival (rPFS), median overall survival (OS) and the median time to cytotoxic chemotherapy, while maintaining health-related quality of life (HR-QOL) and not substantially differing from placebo plus ADT in safety. Although mature OS data are awaited with interest, the addition of apalutamide to ADT extends the treatment options available for standard of care in adult men with mCSPC.

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] In SPARTAN, apalutamide improved metastasis-free and overall survival for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) with a prostate-specific antigen doubling time of ≤10 mo.

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] The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN.

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

Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. [2023] In the SPARTAN study, compared with placebo, apalutamide added to ongoing androgen deprivation therapy significantly prolonged metastasis-free survival (MFS) and time to symptomatic progression in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC). Overall survival (OS) results at the first interim analysis (IA1) were immature, with 104 of 427 (24%) events required for planned final OS analysis. Here, we report the results of a second pre-specified interim analysis (IA2).

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] Apalutamide is a next-generation androgen receptor (AR) inhibitor approved for patients with nonmetastatic castration-resistant prostate cancer (CRPC) and metastatic castration-sensitive prostate cancer. We evaluated the pharmacokinetics, safety, and antitumor activity of apalutamide combined with abiraterone acetate plus prednisone (AA-P) in patients with metastatic CRPC (mCRPC).

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

Apalutamide: First Global Approval. [2019] Apalutamide (ErleadaTM) is a next-generation oral androgen receptor (AR) inhibitor that is being developed by Janssen for the treatment of prostate cancer (PC). It binds directly to the ligand-binding domain of the AR and blocks the effects of androgens. In February 2018, apalutamide received its first global approval in the USA for the treatment of non-metastatic castration-resistant PC (nmCRPC). Apalutamide is undergoing phase III investigation in chemotherapy-naive patients with metastatic CRPC (in combination with abiraterone acetate plus prednisone), patients with high-risk localized or locally advanced PC receiving primary radiation therapy, and in patients with metastatic hormone-sensitive PC and biochemically-relapsed PC. This article summarizes the milestones in the development of apalutamide leading to this first approval in nmCRPC.

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] Apalutamide is a next-generation androgen receptor inhibitor approved for treatment of subjects with high-risk, non-metastatic, castration-resistant prostate cancer (NM-CRPC).

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

Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. [2020] Apalutamide (marketed as Erleada®) is an oral non-steroidal next-generation selective inhibitor of the androgen receptor (AR), and is approved in several countries, including the USA and those of the EU, for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). In men with nmCRPC who were receiving androgen-deprivation therapy (ADT) and had a high risk of metastases in SPARTAN, apalutamide significantly prolonged metastasis-free survival (MFS) compared with placebo, with consistent benefits demonstrated across subgroups. The addition of apalutamide to ongoing ADT significantly prolonged time to metastasis and progression-free survival (PFS) compared with placebo, and maintained health-related quality of life (HR-QOL). Apalutamide was generally well tolerated in SPARTAN, with fatigue being the most frequently reported adverse event. Given the available evidence, apalutamide with ongoing ADT represents an emerging treatment option for patients with nmCRPC who are at high risk of developing metastatic disease.