Antibody-Chemotherapy Combo for Prostate Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Second generation anti-androgens

Must not be taking: Antiretrovirals, Investigational agents

Disqualifiers: Cardiac illness, Uncontrolled infection, 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

Compensation: Varies

Number of Visits: 24

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment combination for prostate cancer that resists standard hormone therapy and has metastasized. The study combines two targeted therapies, pertuzumab and trastuzumab (which help the immune system attack cancer cells), with the chemotherapy drug enzalutamide to determine if they work better together. It seeks participants with prostate cancer that no longer responds to hormone therapy and has spread, even after treatments like enzalutamide or abiraterone. 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 for this trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot be on any other investigational agents for prostate cancer or drugs that interfere with the study drugs. It's best to consult with the trial team or your doctor for specific guidance.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you cannot be on any other investigational agents or drugs that interfere with the study drugs. It's best to consult with the trial team or your doctor for specific guidance.

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

Research has shown that a combination of the drugs pertuzumab, trastuzumab, hyaluronidase-zzxf, and enzalutamide may help treat certain cancers. Studies have found that pertuzumab and trastuzumab, often administered with hyaluronidase-zzxf, are usually well-tolerated. In one study with 500 participants, this combination was compared to a different version of the same treatment. It proved effective and had a safety profile similar to other cancer treatments.

Most side effects were mild, such as tiredness, nausea, and headaches, while serious side effects were less common. Enzalutamide, a drug used in this combination, is also generally well-tolerated but can cause side effects like fatigue, hot flashes, and high blood pressure.

This trial is in phase 2, indicating that there is already some evidence of safety for humans. Phase 2 trials focus more on the treatment's effectiveness and safety. The combination is also approved for other types of cancer, which adds confidence to its safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this antibody-chemotherapy combo for prostate cancer because it combines targeted therapy with hormone treatment. Unlike standard treatments that often focus solely on hormone suppression, this approach uses pertuzumab and trastuzumab, which are antibodies that specifically target cancer cell growth pathways, alongside enzalutamide, a hormone therapy. The added use of hyaluronidase-zzxf allows for more efficient absorption of the antibodies, potentially enhancing treatment effectiveness and minimizing side effects. This innovative combination could provide a more comprehensive attack on cancer cells, offering hope for improved outcomes in prostate cancer treatment.

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

In this trial, participants will receive a combination of the drugs pertuzumab, trastuzumab, and hyaluronidase-zzxf with enzalutamide to treat advanced prostate cancer that no longer responds to hormone therapy. Research has shown that pertuzumab and trastuzumab attach to a protein called HER2 on cancer cells, stopping their growth and aiding the immune system in destroying them. Hyaluronidase-zzxf helps these drugs remain in the body longer, enhancing their effectiveness. Enzalutamide, a chemotherapy drug, prevents cancer cells from growing and spreading. Together, these drugs aim to kill more cancer cells by attacking the disease in different ways. ^{1 2 3 6 7}

Who Is on the Research Team?

Jacob Orme

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults with metastatic castration-resistant prostate cancer that has spread and are resistant to second-generation antiandrogens. Participants must be able to complete questionnaires, provide consent, have certain blood levels within normal ranges, and a good performance status. Pregnant or nursing individuals, those with severe diseases or infections, recent thromboembolic events, other active cancers (with exceptions), known drug sensitivities related to the study drugs, uncontrolled illnesses like heart failure or arrhythmias can't join.

Inclusion Criteria

Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (=< 5 x ULN for patients with liver involvement)

I can take care of myself and am up and about more than half of my waking hours.

Willingness to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

Exclusion Criteria

I have had a heart attack in the last 6 months or have heart failure needing ongoing treatment.

I have not had a blood clot in the last 60 days.

My mild nerve damage has been stable for 3 months after my last treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneously on day 1 of each cycle and enzalutamide orally once daily on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 3 months until progressive disease, then every 6 months thereafter.

Up to 2 years

Every 3 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• Hyaluronidase-zzxf
• Pertuzumab
• Trastuzumab

Trial Overview The TraPPer Study is testing the combination of pertuzumab, trastuzumab (both monoclonal antibodies targeting HER2 on cancer cells), hyaluronidase-zzxf (to enhance the effect and administration of these antibodies), and enzalutamide (a chemotherapy drug). The goal is to see if this combo works better at killing prostate cancer cells that no longer respond to typical hormone treatments.

How Is the Trial Designed?

Group I: Treatment (HP, enzalutamide) Experimental Treatment 8 Interventions

Patients receive pertuzumab, trastuzumab, and hyaluronidase-zzxf SC on day 1 of each cycle and enzalutamide PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO, biopsy, CT, and MRI scans and collection of blood samples throughout the study.

Enzalutamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Xtandi for:

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

Approved in European Union as Xtandi for:

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

Approved in Canada as Xtandi for:

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

Approved in Japan as Xtandi for:

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

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Tasquinimod, an orally administered drug, has shown strong anti-cancer effects in both laboratory and animal studies, making it a promising option for treating advanced prostate cancer.

Early phase clinical trials indicate that tasquinimod is well-tolerated by patients and is associated with prolonged progression-free survival, although further results from ongoing Phase III trials are still awaited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of tasquinimod in the treatment of advanced prostate cancer. Williamson, SC., Hartley, AE., Heer, R.[2022]

A study involving 808 patients with HER-2 positive breast cancer showed that adding pertuzumab to trastuzumab and docetaxel significantly improved overall survival, with a 3-year survival rate increase of 10% to 15%.

While pertuzumab did not worsen cardiac toxicity in patients with low cardiovascular risk, it was associated with increased side effects such as severe diarrhea and skin disorders, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]

The FeDeriCa study demonstrated that the subcutaneous formulation of pertuzumab and trastuzumab is non-inferior to the intravenous version in terms of serum drug levels, indicating it can effectively deliver the same therapeutic benefits in patients with HER2-positive early breast cancer.

Safety profiles were comparable between the subcutaneous and intravenous groups, with similar rates of serious adverse events, suggesting that the new formulation is a safe alternative for patients undergoing neoadjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Tan, AR., Im, SA., Mattar, A., et al.[2021]

Combining atezolizumab, an anti-PD-L1 immunotherapy, with enzalutamide, an androgen receptor antagonist, did not improve survival rates in patients with metastatic prostate cancer.

Further research is needed to understand the mechanisms of resistance to immunotherapy in the prostate tumor microenvironment, which may help improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-L1 plus enzalutamide does not improve overall survival in prostate cancer. Siddiqui, BA., Subudhi, SK., Sharma, P.[2023]

In three cases of metastatic castration-resistant prostate cancer (mCRPC), patients showed significant responses to anti-PD-1 immunotherapy after being treated with bipolar androgen therapy (BAT) and enzalutamide, suggesting a potential strategy for enhancing immunotherapy effectiveness.

Two of the patients had inactivating mutations in HR DNA repair genes (BRCA2, ATM), indicating that specific genetic profiles may influence the success of immune checkpoint blockade in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extreme responses to immune checkpoint blockade following bipolar androgen therapy and enzalutamide in patients with metastatic castration resistant prostate cancer. Markowski, MC., Shenderov, E., Eisenberger, MA., et al.[2021]

The FDA approved Phesgo, a subcutaneous injection combining pertuzumab, trastuzumab, and hyaluronidase-zzxf, for treating HER2-positive early-stage and metastatic breast cancer, based on the FeDeriCa trial which showed that the subcutaneous formulation is pharmacokinetically comparable to the intravenous versions.

The study demonstrated that the subcutaneous treatment had similar efficacy to intravenous treatments, with common side effects including alopecia, nausea, and diarrhea, supporting its use across all approved indications for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf Injection for Subcutaneous Use in Patients with HER2-positive Breast Cancer. Gao, JJ., Osgood, CL., Gong, Y., et al.[2022]

The ENZAMET phase III trial demonstrated that adding enzalutamide to standard treatment significantly prolongs survival in men with metastatic hormone-sensitive prostate cancer.

Enzalutamide is more effective than older nonsteroidal antiandrogen drugs, highlighting its potential as a superior treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide Bests Older NSAAs in mHSPC. [2021]

In men with metastatic hormone-sensitive prostate cancer, enzalutamide, when combined with androgen-deprivation therapy, significantly prolonged radiographic progression-free survival compared to a placebo.

This finding highlights the efficacy of enzalutamide as an androgen-receptor inhibitor in improving outcomes for patients undergoing treatment for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eyeing Enzalutamide for Hormone-Sensitive Prostate Cancer. [2020]

In a phase II study involving 42 patients with castration-resistant prostate cancer (CRPC) who had progressed after chemotherapy, pertuzumab was well tolerated, with diarrhea being the most common side effect (61% of patients).

Although no patients achieved complete or partial responses, five out of 30 patients with assessable efficacy had stable disease for at least 23 weeks, and retrospective analysis indicated that pertuzumab treatment may have prolonged survival compared to historical controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of single-agent pertuzumab (rhuMAb 2C4), a human epidermal growth factor receptor dimerization inhibitor, in castration-resistant prostate cancer after progression from taxane-based therapy. Agus, DB., Sweeney, CJ., Morris, MJ., et al.[2016]

The combination of enzalutamide (ENZ) and prostate-specific membrane antigen antibody drug conjugate (PSMA ADC) significantly inhibited tumor growth in advanced castration-resistant prostate cancer (CRPC) models, showing better efficacy than either treatment alone.

In a preclinical study with patient-derived xenografts, the PSMA ADC+ENZ combination not only reduced tumor size but also resulted in the most pronounced survival benefits, with no deaths observed in the combination group, suggesting a promising new treatment strategy for CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of PSMA ADC to enzalutamide therapy significantly improves survival in in vivo model of castration resistant prostate cancer. DiPippo, VA., Nguyen, HM., Brown, LG., et al.[2021]

Trastuzumab emtansine (T-DM1) is an effective treatment for HER2-positive breast cancers, but its effectiveness can be reduced due to the development of resistance.

The resistance to T-DM1 is mediated by the HER3 ligand neuregulin, but this can be countered by using pertuzumab, which inhibits HER2 dimerization, potentially restoring the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab protects the achilles' heel of trastuzumab--emtansine. Gwin, WR., Spector, NL.[2018]

A Phase I study involving 24 healthy volunteers found that intravenous administration of rHuPH20 (up to 30,000 U) was well tolerated, with no serious adverse events reported, indicating a favorable safety profile.

The pharmacokinetics showed that rHuPH20 was rapidly cleared from the plasma, with plasma hyaluronan concentrations increasing in a dose-dependent manner and returning to baseline within one week, suggesting effective metabolism and clearance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Recombinant Human Hyaluronidase PH20 Administered Intravenously in Healthy Volunteers. Printz, MA., Dychter, SS., DeNoia, EP., et al.[2022]

In preclinical models of metastatic castration-resistant prostate cancer, the combination of NLG207 (a HIF-1α inhibitor) and enzalutamide significantly reduced tumor volume by 93% after 3 weeks, indicating strong efficacy against enzalutamide resistance.

The addition of NLG207 enhanced the effectiveness of enzalutamide, decreasing the median tumor growth rate by 51%, suggesting that targeting both HIF-1α and androgen receptor pathways could be a promising strategy for overcoming treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor Activity of NLG207 (Formerly CRLX101) in Combination with Enzalutamide in Preclinical Prostate Cancer Models. Schmidt, KT., Chau, CH., Strope, JD., et al.[2022]

Enzalutamide significantly improves overall survival and radiographic progression-free survival in men with metastatic, castration-resistant prostate cancer (mCRPC), as shown in two major randomized trials (AFFIRM and PREVAIL) involving patients who had previously undergone chemotherapy and those who were chemotherapy naive.

While enzalutamide is generally safe and effective, it can cause side effects like fatigue and has specific safety concerns, such as an increased risk of seizures and falls, particularly in older patients (≥ 75 years).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. Graff, JN., Gordon, MJ., Beer, TM.[2021]

Citations

1. phesgo-hcp.com phesgo-hcp.com/clinical-data/clinical-results.html

PHESGO clinical trial results for HER2+ breast cancer Phase III, randomized, open-label non-inferiority trial that evaluated the PK, efficacy, and safety of PHESGO vs IV PERJETA® (pertuzumab) + trastuzumab1-3.

2. phesgo.com phesgo.com/about-phesgo/clinical-trial-results.html

Clinical trial results with PHESGO® (pertuzumab ... The main study of PHESGO was a comparison of PHESGO vs IV PERJETA (pertuzumab) + Herceptin (trastuzumab). This clinical study included 500 people with HER2+ ...

3. cancer.gov cancer.gov/about-cancer/treatment/types/targeted-therapies/approved-drug-list

Targeted Therapy Drug List by Cancer Type - NCI Targeted therapy is a type of cancer treatment that targets the changes in cancer cells that help them grow, divide, and spread.

4. mayo.edu mayo.edu/research/clinical-trials/cls-20541946

Pertuzumab, Trastuzumab, Hyaluronidase-zzxf and ... This phase II trial tests how well pertuzumab, trastuzumab, hyaluronidase-zzxf and enzalutamide works in treating patients with castration-resistant prostate ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-10773

Pertuzumab, Trastuzumab, Hyaluronidase-zzxf and ... This phase II trial tests how well pertuzumab, trastuzumab, hyaluronidase-zzxf and enzalutamide works in treating patients with castration-resistant ...

6. oncolink.org oncolink.org/cancer-treatment/oncolink-rx/pertuzumab-trastuzumab-and-hyaluronidase-zzxf-phesgo

Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf ... Pertuzumab and trastuzumab target HER2 positive cancer cells. HER2 receptors on cells send signals telling the cell to grow and divide. Cancers ...

7. clin.larvol.com clin.larvol.com/trial-detail/NCT05730712

Pertuzumab, Trastuzumab, Hyaluronidase-zzxf and ... Pertuzumab, Trastuzumab, Hyaluronidase-zzxf and Enzalutamide for Treatment of Metastatic Castration-Resistant Prostate Cancer ... Prostate Cancer Clinical Trials ...