Galunisertib + Enzalutamide for Prostate Cancer

Recruiting at 3 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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to compare the progression free survival (PFS) of patients with metastatic castration-resistant prostate cancer treated with enzalutamide in combination with LY2157299 (Arm 1) versus enzalutamide alone (Arm 2).

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.

What data supports the effectiveness of the drug Enzalutamide for prostate cancer?

Research shows that Enzalutamide, a drug that blocks male hormones, significantly improves survival and delays disease progression in men with advanced prostate cancer. ^{1 2 3 4 5}

Is the combination of Galunisertib and Enzalutamide safe for humans?

Enzalutamide, also known as Xtandi, is generally well-tolerated in men with prostate cancer, with studies showing it can be safely used and improve survival. However, specific safety data for the combination of Galunisertib and Enzalutamide is not provided in the available research. ^{1 3 4 6 7}

How is the drug combination of Galunisertib and Enzalutamide unique for treating prostate cancer?

The combination of Galunisertib and Enzalutamide is unique because it pairs Enzalutamide, an oral drug that blocks male hormones from stimulating cancer growth, with Galunisertib, which may have different mechanisms of action, potentially offering a novel approach to treating prostate cancer compared to using Enzalutamide alone. ^{1 2 4 8 9}

Research Team

Channing Paller, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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 am 18 years old or older.

I can do all my daily activities without help.

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

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

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

Treatment Details

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.

Participant Groups

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+

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

Findings from Research

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]

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 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 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 (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]

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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. [2022]

2. Switzerland 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. [2022]

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

Enzalutamide for patients with metastatic castration-resistant prostate cancer. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. Switzerland 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. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. [2021]

8. 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]

9. England 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). [2022]