Abiraterone + Prednisone +/- Abemaciclib for Prostate Cancer

(CYCLONE 2 Trial)

Not currently recruiting at 208 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: Eli Lilly and Company

Must be taking: Abiraterone, Prednisone

Must not be taking: CYP17 inhibitors, CDK 4/6 inhibitors

Disqualifiers: Heart disease, Liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 28

Duration: Up to 60 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding abemaciclib, a type of cancer treatment, to the standard regimen of abiraterone acetate and prednisone is safe and more effective for treating metastatic castration-resistant prostate cancer. The researchers aim to determine if this combination can better manage cancer that has spread and no longer responds to hormone therapy. Participants will receive either the experimental drug combination or a placebo with the standard treatment. Ideal candidates have prostate cancer that has spread to bones or other tissues and continues to progress despite ongoing hormone therapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had prior treatment with certain prostate cancer drugs or be currently enrolled in another clinical study.

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

Research has shown that abemaciclib is generally well-tolerated by patients. In one study, patients who took abemaciclib with abiraterone experienced a median time of 22 months before their cancer progressed. This finding suggests that the combination is both effective and manageable for many individuals. Previous patients have demonstrated that abemaciclib can be tolerated even when used alone in heavily treated groups.

Abiraterone acetate, often used with prednisone, has received FDA approval for treating prostate cancer, indicating its well-established safety. Most patients tolerate it well, though some may experience side effects like high blood pressure or changes in liver function. Prednisone, a steroid commonly used to reduce inflammation, is generally safe at low doses for most patients.

Overall, the combination of these treatments has proven to be manageable, with side effects similar to those expected in cancer treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because abemaciclib offers a unique approach by specifically targeting proteins called CDK4 and CDK6, which are involved in cell division and growth. Unlike traditional treatments like hormone therapy or chemotherapy, abemaciclib can potentially slow down cancer cell proliferation more precisely. Additionally, the combination of abemaciclib with abiraterone acetate and prednisone might enhance the effectiveness of existing therapies, providing a more comprehensive attack on cancer cells. This combo could lead to improved outcomes for patients by potentially delaying disease progression and reducing symptoms more effectively than current options alone.

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

In this trial, participants will receive either abemaciclib combined with abiraterone and prednisone or a placebo with abiraterone and prednisone. Research has shown that adding abemaciclib to the treatment of metastatic castration-resistant prostate cancer, alongside abiraterone and prednisone, may be beneficial. Specifically, studies found that this combination can prevent cancer growth for about 22 months, compared to 20.3 months with only abiraterone and prednisone. This suggests it might help delay cancer progression. Abemaciclib blocks certain proteins, CDK4 and CDK6, which aid cancer cell growth, potentially slowing or stopping the spread of cancer cells. ^{1 6 7 8 9}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

Men with advanced prostate cancer that has spread and is resistant to hormone therapy can join. They must have a specific type of prostate cancer confirmed by tests, worsening disease despite ongoing hormone treatment, and their body should be functioning well enough (ECOG 0-1). Men who've had certain other treatments or have serious heart, liver, or digestive problems cannot participate.

Inclusion Criteria

Progressive disease at study entry demonstrated during continuous androgen-deprivation therapy (ADT)/post orchiectomy defined as one or more of the following: PSA progression, Radiographic progression per Response Evaluation Criteria in Solid Tumors (RECIST)1.1 for soft tissue and/or per Prostate Cancer Working Group 3 (PCWG3) for bone, with or without PSA progression, Have adequate organ function, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

My prostate cancer has spread, confirmed by a bone scan or CT/MRI.

My prostate cancer is confirmed by tissue analysis.

Exclusion Criteria

I have not taken abemaciclib or any CDK 4 & 6 inhibitors before.

I have had chemotherapy or specific treatments for advanced prostate cancer, but not for all cancer spots.

I have a stomach or intestine problem that makes it hard for me to absorb medicine or swallow big pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib or placebo in combination with abiraterone acetate and prednisone on a continuous dosing schedule until progression or discontinuation

Up to 60 months

Continuous dosing on a 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Abiraterone Acetate
• Prednisone

Trial Overview The trial is testing the safety and effectiveness of adding abemaciclib to the standard treatment for this stage of prostate cancer: abiraterone acetate plus prednisone. Some participants will receive a placebo instead of abemaciclib to compare outcomes.

How Is the Trial Designed?

Group I: Abemaciclib Experimental Treatment 3 Interventions

Participants received 200 milligrams (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.

Group II: Placebo Placebo Group 3 Interventions

Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.

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

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic high-risk castration-sensitive prostate cancer

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Newly diagnosed high-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic castration-sensitive prostate cancer

Approved in Japan as Zytiga for:

• Prostate cancer

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead 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 3 trial with 1088 patients, abiraterone acetate plus prednisone significantly improved overall survival compared to placebo plus prednisone, with a median survival of 34.7 months versus 30.3 months, indicating its efficacy in treating chemotherapy-naive castration-resistant prostate cancer.

The treatment was associated with a manageable safety profile, although there were some increased risks of grade 3-4 adverse events, such as cardiac disorders and elevated liver enzymes, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Ryan, CJ., Smith, MR., Fizazi, K., et al.[2022]

In a clinical trial involving 164 men with metastatic castration-resistant prostate cancer, abiraterone acetate combined with prednisone (5 mg twice daily) or dexamethasone (0.5 mg once daily) effectively minimized mineralocorticoid excess, which is important for patient safety.

While abiraterone with dexamethasone showed promising efficacy, it was also linked to adverse metabolic effects, such as increased insulin resistance and decreased bone mineral density, highlighting the need for careful monitoring of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the Safety of Glucocorticoid Regimens in Combination With Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer: A Randomized, Open-label Phase 2 Study. Attard, G., Merseburger, AS., Arlt, W., et al.[2022]

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

Abiraterone acetate, in combination with prednisone, received full FDA approval for treating metastatic castration-resistant prostate cancer (mCRPC) based on the COU-AA-302 trial, which involved 1,088 patients and showed a significant improvement in radiographic progression-free survival (rPFS) compared to placebo (8.3 months vs. not reached).

The trial also indicated a favorable trend in overall survival (OS) for patients receiving abiraterone acetate, although it did not reach statistical significance, confirming the drug's efficacy and safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Ning, YM., Maher, VE., et al.[2018]

In a phase 3 trial involving 1199 patients, the addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly improved overall survival, with a median survival not reached in the abiraterone group compared to 34.7 months in the placebo group.

The study also showed that patients receiving abiraterone had a median radiographic progression-free survival of 33.0 months, compared to 14.8 months in the placebo group, indicating a strong benefit in delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. Fizazi, K., Tran, N., Fein, L., et al.[2022]

In a multicenter early-access trial involving 2314 patients with metastatic castration-resistant prostate cancer, abiraterone acetate combined with prednisone showed a median time to PSA progression of 8.5 months and a median time to clinical progression of 12.7 months, indicating its efficacy in delaying disease progression after chemotherapy.

The study reported that 41% of patients experienced grade 3 or 4 treatment-related adverse events, with hepatotoxicity and hypertension being the most common, but no new safety signals were identified, suggesting that abiraterone acetate is generally safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy: final analysis of a multicentre, open-label, early-access protocol trial. Sternberg, CN., Castellano, D., Daugaard, G., et al.[2022]

In a phase II study involving 41 men with metastatic castration-resistant prostate cancer, increasing the dose of abiraterone acetate from 1000 mg to 2000 mg daily did not result in any significant clinical benefit, as no patients showed a prostate-specific antigen (PSA) decline of 30% or more after 12 weeks.

The study found that factors such as lower baseline circulating androgen levels and individual differences in drug metabolism may contribute to resistance against standard-dose abiraterone therapy, suggesting that simply increasing the dose is not an effective strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. Friedlander, TW., Graff, JN., Zejnullahu, K., et al.[2018]

In a study of 1088 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate combined with prednisone significantly improved radiographic progression-free survival (rPFS) compared to prednisone alone, with a median rPFS of 16.5 months versus 8.2 months.

Abiraterone acetate also showed a trend towards improved overall survival (OS) with a median of 35.3 months compared to 30.1 months for prednisone, indicating a potential benefit in prolonging life, while maintaining a favorable safety profile over long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). Rathkopf, DE., Smith, MR., de Bono, JS., et al.[2022]

Abiraterone acetate significantly improves overall survival and radiographic progression-free survival in men with metastatic castration-resistant prostate cancer (CRPC) when combined with prednisone, based on results from a multinational phase III study involving men who had previously received docetaxel.

The treatment is generally well-tolerated, although it can cause side effects like hypokalaemia and hypertension; however, serious adverse events were relatively low in the phase III studies, indicating it is a viable option for managing metastatic CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. Hoy, SM.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38512117/

A Signal-Finding Study of Abemaciclib in Heavily ... Efficacy analyses are as follows: ORR without concurrent bone progression: 6.8%; disease control rate: 45.5%; median time to PSA progression: ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41167216/

Abemaciclib plus abiraterone in patients with metastatic ... Median radiographic progression-free survival was 22·0 months (95% CI 19·3-27·5) for abemaciclib plus abiraterone and 20·3 months (16·5-24·4) for placebo plus ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03706365

NCT03706365 | A Study of Abiraterone Acetate Plus ... This study is being done to see how safe and effective abemaciclib is when given together with abiraterone acetate plus prednisone in participants with ...

4. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00475-9/abstract

Abemaciclib plus abiraterone in patients with metastatic ... Abemaciclib, a potent CDK4 and CDK6 inhibitor, has shown antitumour activity in prostate cancer models and in patients with metastatic castration-resistant ...

5. aacrjournals.org aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-23-3436/3441478/ccr-23-3436.pdf

A Signal-Finding Study of Abemaciclib in Heavily Pretreated ... Results: At trial entry, 40 (90.9%) of 44 patients had objective radiographic disease progression, 4 (9.1%) had prostate-specific antigen (PSA)–only progression ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05288166

NCT05288166 | A Study of Abemaciclib (LY2835219) With ... The purpose of this study is to learn whether adding abemaciclib to abiraterone plus prednisone prolongs the time before prostate cancer gets worse.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204525004759

Abemaciclib plus abiraterone in patients with metastatic ... Abemaciclib, a potent CDK4 and CDK6 inhibitor, has shown antitumour activity in prostate cancer models and in patients with metastatic castration-resistant ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04408924?term=AREA%5BExpandedAccessNCTId%5DNCT03763604&rank=7&tab=results

Study Results | Abemaciclib (LY2835219) in Men With ... A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11145166/

A Signal-Finding Study of Abemaciclib in Heavily ... Conclusions: Abemaciclib monotherapy was well tolerated and showed clinical activity in this heavily pretreated population, nearly half with visceral ...