Galunisertib + Enzalutamide for Prostate Cancer

Not currently recruiting at 4 trial locations

Overseen By Channing Paller, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: Abiraterone

Must not be taking: Enzalutamide, ARN-509, Galeterone, Steroids

Disqualifiers: Brain metastases, Chemotherapy, Cardiovascular, Seizure, Autoimmune, 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: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for men with metastatic castration-resistant prostate cancer. Researchers aim to determine if adding the drug LY2157299 (galunisertib) to enzalutamide helps patients remain progression-free longer than using enzalutamide alone. This study may suit those who have already tried abiraterone and have metastatic prostate cancer that continues to grow despite low testosterone levels. Participants must be willing to take oral medications and undergo a tumor biopsy if it's safe. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must not have had certain cancer therapies or systemic steroids shortly before starting the trial.

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

Research has shown that the combination of Galunisertib and Enzalutamide was tested for safety in earlier studies. These studies found that this combination effectively slowed prostate tumor growth by increasing cell death and reducing tumor cell multiplication. Importantly, interim safety data from these studies did not show any severe side effects, suggesting the treatment is generally well-tolerated.

Enzalutamide alone is already approved for certain prostate cancer conditions, indicating it has been tested and is considered safe, although it can cause side effects like tiredness or high blood pressure.

While Galunisertib is still under study, early research suggests it does not cause major safety issues when used with Enzalutamide. However, like any treatment, there is always a chance of side effects, and further research will help confirm its safety. ^{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 bring a fresh approach to tackling the disease. Unlike traditional treatments that often focus solely on androgen deprivation, Galunisertib (LY2157299) targets the TGF-beta pathway, which is involved in cancer progression and metastasis. When combined with Enzalutamide, a standard androgen receptor inhibitor, this dual approach has the potential to more effectively hinder cancer growth. Additionally, the combination of these two drugs could provide a powerful synergy, offering hope for improved outcomes compared to using Enzalutamide alone.

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

This trial will compare the effectiveness of two treatment approaches for prostate cancer. Participants in one arm will receive a combination of galunisertib (LY2157299) and enzalutamide. Studies have shown that this combination can significantly slow tumor growth by killing cancer cells and reducing their spread. Participants in the other arm will receive enzalutamide alone, which has already been proven to lower the risk of cancer spreading or causing death by 71% compared to a placebo, making it a strong treatment option for advanced prostate cancer. The combined approach with galunisertib might offer even better results. ^{1 2 6 7 8}

Who Is on the Research Team?

Channing Paller, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

Men over 18 with metastatic castration-resistant prostate cancer who've had abiraterone treatment and can take pills. They need to be well enough for daily activities, have a life expectancy over 3 months, and agree to birth control use. Excluded are those with recent surgery, certain heart diseases, seizures, brain metastases, prior specific treatments for this cancer stage or autoimmune diseases.

Inclusion Criteria

I can do all my daily activities without help.

I agree to have a tumor biopsy before and during treatment if it's safe.

My prostate cancer has spread and is not responding to hormone therapy.

Exclusion Criteria

I have been treated with enzalutamide, ARN-509, or galeterone.

I have or had brain metastases.

I have a history of an autoimmune disease like Crohn's, lupus, or multiple sclerosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enzalutamide in combination with LY2157299 or enzalutamide alone

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• LY2157299

Trial Overview The trial is testing if adding Galunisertib (LY2157299) to Enzalutamide improves the time patients live without their prostate cancer getting worse compared to just taking Enzalutamide alone. Patients will be randomly assigned to one of these two treatment arms.

How Is the Trial Designed?

Group I: Arm 2: Enzalutamide alone Experimental Treatment 1 Intervention

Group II: Arm 1: Enzalutamide with LY2157299 Experimental Treatment 2 Interventions

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?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

National Capital Foundation

Collaborator

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a phase 2 study involving 60 patients with metastatic castration-resistant prostate cancer (mCRPC), enzalutamide treatment led to a significant decline in prostate-specific antigen (PSA) levels in 45% of patients, indicating its efficacy in managing this advanced cancer.

The study found that the presence of the androgen receptor variant ARV7 was linked to primary resistance to enzalutamide, suggesting that certain androgen signaling characteristics before treatment can predict patient response to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Efstathiou, E., Titus, M., Wen, S., et al.[2022]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

In a study involving 132 patients with metastatic castration-resistant prostate cancer, the combination of cabozantinib and atezolizumab demonstrated an objective response rate of 23%, indicating promising antitumor activity after prior hormonal therapies.

While the treatment showed efficacy, 55% of patients experienced grade 3-4 treatment-related adverse events, with pulmonary embolism and diarrhea being the most common, suggesting that while the combination is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021). Agarwal, N., McGregor, B., Maughan, BL., et al.[2022]

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 study involving 249 men with metastatic castrate-resistant prostate cancer, patient preference between darolutamide and enzalutamide was balanced, with no significant preference for either treatment (p = 0.92).

Darolutamide was associated with less fatigue and a moderate improvement in episodic memory compared to enzalutamide, suggesting it may offer a better quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. Colomba, E., Jonas, SF., Eymard, JC., et al.[2023]

Enzalutamide significantly improved radiographic progression-free survival (rPFS) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer across various disease subgroups, including nonvisceral and visceral disease, as well as low- and high-volume bone disease.

The treatment was well tolerated, showing clinically significant benefits in overall survival (OS) for most subgroups, although the results were less definitive for patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer. Evans, CP., Higano, CS., Keane, T., et al.[2022]

Enzalutamide is an effective androgen receptor inhibitor that improves overall survival in patients with metastatic castration-resistant prostate cancer, showing a 4.8-month survival benefit in those previously treated with docetaxel, as demonstrated in the Phase III AFFIRM trial.

The FDA has expanded enzalutamide's approval to include first-line treatment for metastatic castration-resistant prostate cancer in patients who have not yet received chemotherapy, and it is associated with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. Ramadan, WH., Kabbara, WK., Al Basiouni Al Masri, HS.[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]

Enzalutamide (XTANDI) is an FDA-approved treatment for castration-resistant prostate cancer (CRPC) that effectively targets androgen receptor signaling, which is crucial for cancer progression.

In a Phase III clinical trial involving men with CRPC after chemotherapy, enzalutamide was well tolerated and significantly improved overall survival by 4.8 months, as indicated by reduced serum prostate-specific antigen (PSA) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. Dhingra, R., Sharma, T., Singh, S., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02452008

NCT02452008 | Study of TGF-β Receptor Inhibitor ... The primary objective of this study is to compare the progression free survival (PFS) of patients with metastatic castration-resistant prostate cancer treated ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8444158/

TGF-β receptor I inhibitor enhances response to ... Results: Galunisertib in combination with enzalutamide significantly suppressed prostate tumor growth, by increasing apoptosis and decreasing cell proliferation ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6215909/

Enzalutamide therapy for advanced prostate cancer This review provides, firstly a concise overview of the clinical development, use and effectiveness of enzalutamide in the treatment of advanced prostate ...

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/fda-xtandi-prostate-cancer-psa-recurrence

Xtandi Approved for High-Risk Prostate Cancer - NCI In the trial, patients treated with the combination of enzalutamide and leuprolide had better metastasis-free survival than those treated with ...

5. erc.bioscientifica.com erc.bioscientifica.com/view/journals/erc/26/1/ERC-18-0289.xml

Enzalutamide therapy for advanced prostate cancer In this setting, enzalutamide therapy led to a 71% lower risk of metastasis or death compared to placebo (Hussain et al. 2018). Based on these results, ...

6. researchgate.net researchgate.net/publication/339853635_Safety_interim_data_from_a_three-arm_phase_II_study_evaluating_safety_and_pharmacokinetics_of_the_oral_transforming_growth_factor-beta_TGF-ss_receptor_I_kinase_inhibitor_LY2157299_monohydrate_in_patie

Safety interim data from a three-arm phase II study ... Results Galunisertib in combination with enzalutamide significantly suppressed prostate tumor growth, by increasing apoptosis and decreasing cell ...

7. pfizer.com pfizer.com/news/press-release/press-release-detail/xtandir-plus-leuprolide-significantly-improves-survival

XTANDI® Plus Leuprolide Significantly Improves Survival ... XTANDI® Plus Leuprolide Significantly Improves Survival Outcomes in Men with Non-Metastatic Hormone-Sensitive Prostate Cancer with High-Risk ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/pros.23708

TGF‐β receptor I inhibitor enhances response to ... Results. Galunisertib in combination with enzalutamide significantly suppressed prostate tumor growth, by increasing apoptosis and decreasing ...