Abemaciclib + Abiraterone for Prostate Cancer

(CYCLONE 3 Trial)

Not currently recruiting at 526 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 3

Sponsor: Eli Lilly and Company

Must be taking: Androgen deprivation therapy

Must not be taking: CDK4 & 6 inhibitors

Disqualifiers: Cardiovascular disease, Liver disease, CNS metastasis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 48 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding the drug abemaciclib (a type of cancer treatment) to the current regimen of abiraterone and prednisone can delay prostate cancer progression. Participants will receive either abemaciclib or a placebo alongside their regular medication. The trial seeks individuals with prostate cancer that has metastasized, particularly those with multiple bone or organ tumors. It is designed for those who have begun hormone therapy but have not previously tried abemaciclib or similar drugs. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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 must not have had prior treatment with abemaciclib or any other CDK4 & 6 inhibitor, and you should not have received any prior systemic therapy for metastatic prostate cancer, except for ADT and first-generation anti-androgen.

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

Previous studies have shown that abemaciclib is safe for patients. Research indicates that using abemaciclib with abiraterone and prednisone does not significantly increase serious side effects. Most reported side effects were mild or moderate, such as diarrhea or fatigue.

Abiraterone, the other main treatment in this combination, has FDA approval for prostate cancer, so its safety is well-known. People taking abiraterone often experience high blood pressure or changes in liver function, but regular check-ups usually manage these issues.

Overall, while every medication can have side effects, studies have generally found the combination of abemaciclib and abiraterone to be well-tolerated. Participants should discuss any concerns with their doctor to determine if this trial might be a good fit for them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about the combination of abemaciclib and abiraterone for prostate cancer because it offers a new approach to treatment. While abiraterone is already used to target androgen production, abemaciclib adds another layer by inhibiting cyclin-dependent kinases 4 and 6 (CDK4/6), which are crucial for cancer cell growth and division. This dual approach has the potential to more effectively slow down or stop tumor progression compared to standard hormone therapies alone. Additionally, using abemaciclib alongside abiraterone could enhance the overall effectiveness and provide a new option for patients who may not respond well to existing treatments.

What evidence suggests that adding abemaciclib to abiraterone might be an effective treatment for prostate cancer?

In this trial, participants will receive either a combination of abemaciclib and abiraterone or a placebo with abiraterone to treat prostate cancer. Research has examined the effectiveness of combining abemaciclib with abiraterone for this purpose. Abemaciclib targets proteins that aid cancer cell growth. However, recent studies found that adding abemaciclib to abiraterone did not significantly slow the progression of prostate cancer. The treatment did not improve the duration during which the cancer remains stable on imaging tests. There was no negative effect on overall survival, indicating the treatment was safe but not more effective than using abiraterone alone. ^{1 3 4 6 7}

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 prostate cancer that has spread and is expected to respond to hormone therapy can join. They must have started hormone treatment before joining, have a good performance status, and not received certain other treatments for metastatic prostate cancer or have serious heart conditions.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer is prostate adenocarcinoma.

I have started hormone therapy for my cancer and will continue it during the study.

Exclusion Criteria

I have a history of heart-related fainting, irregular heartbeats, or sudden cardiac arrest but stable atrial arrhythmia is well-controlled with medication.

My brain metastases have been treated and stable for 8 weeks, and I haven't taken corticosteroids for 2 weeks.

My prostate cancer has spread and my testosterone levels are very low.

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 and Prednisone

48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Abiraterone

Trial Overview The study tests if adding abemaciclib to the standard treatment of abiraterone plus prednisone/prednisolone extends the time before prostate cancer worsens. Participants will be observed for up to 60 months.

How Is the Trial Designed?

Group I: Abemaciclib Experimental Treatment 3 Interventions

Participants received 200 milligram (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg 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 Active Control 3 Interventions

Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg 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 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 (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

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 the IPATential150 trial involving 1097 patients with metastatic castration-resistant prostate cancer, adding ipatasertib to abiraterone and prednisone significantly improved radiographic progression-free survival for patients with PTEN-loss tumors.

While ipatasertib was associated with a higher rate of serious adverse events and treatment discontinuation compared to placebo, its overall safety profile was considered tolerable, suggesting that with proper management, the side effects could be mitigated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Ipatasertib Plus Abiraterone vs Placebo Plus Abiraterone in Metastatic Castration-resistant Prostate Cancer. Matsubara, N., de Bono, J., Sweeney, C., et al.[2023]

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]

Oral abiraterone acetate (Zytiga®) effectively inhibits androgen biosynthesis, which is crucial for the progression of metastatic castration-resistant prostate cancer (mCRPC), and has been shown to prolong overall survival and radiographic progression-free survival in large phase 3 trials.

In combination with prednisone, abiraterone acetate has a manageable safety profile and is a convenient once-daily treatment option, making it a significant first-line therapy for men with mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer. Scott, LJ.[2019]

In a study of 1199 men with metastatic castration-sensitive prostate cancer, treatment with abiraterone acetate plus prednisone (AA+P) significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) compared to placebo, particularly in patients with lung metastases.

Patients with visceral metastases (VM) who received AA+P had a median OS of 55.4 months versus 33.0 months for those on placebo, and a median rPFS of 30.7 months compared to 18.3 months, indicating that AA+P is an effective treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of abiraterone acetate plus prednisone in patients with castration-sensitive prostate cancer and visceral metastases over four years of follow-up: A post-hoc exploratory analysis of the LATITUDE study. Baciarello, G., Özgüroğlu, M., Mundle, S., 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 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]

In a Swedish observational study of 119 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate treatment resulted in similar overall survival rates compared to those seen in the pivotal clinical trial, despite a shorter median treatment duration of 5.6 months versus 7.3 months in the trial.

The findings suggest that while Swedish patients may have characteristics that could limit their treatment benefits, they still achieve comparable survival outcomes, indicating a potentially more cost-effective use of abiraterone in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. Svensson, J., Andersson, E., Persson, U., et al.[2017]

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[2022]

Citations

1. 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 ...

2. 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 ...

3. 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 ...

4. urotoday.com urotoday.com/conference-highlights/asco-2024/asco-2024-prostate-cancer/152472-asco-2024-cyclone-2-a-phase-3-study-of-abemaciclib-with-abiraterone-in-patients-with-mcrpc.html

ASCO 2024: CYCLONE 2: A Phase 3 study of Abemaciclib ... The addition of abemaciclib to abiraterone did not significantly improve radiographic progression free survival in patients with mCRPC · Safety ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5001

CYCLONE 2: A phase 3 study of abemaciclib with ... Conclusions: In patients with mCRPC, adding abemaciclib to abiraterone did not significantly increase rPFS. While no OS detriment was observed, ...

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

Study Results | Abemaciclib (LY2835219) in Men With ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04408924/

Clinical Trial: NCT04408924 The study will evaluate how safe and effective abemaciclib is when given to participants whose metastatic prostate cancer progresses after they ...