A Study of Abemaciclib (LY2835219) With Abiraterone in Men With Prostate Cancer That Has Spread to Other Parts of the Body and is Expected to Respond to Hormonal Treatment (Metastatic Hormone-Sensitive Prostate Cancer) (CYCLONE 3)

• ClinicalTrials.gov Identifier: NCT05288166
• Recruitment Status: Recruiting
• First Posted: March 21, 2022
• Last Update Posted: May 24, 2023
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: March 10, 2022
• First Posted Date: March 21, 2022
• Last Update Posted Date: May 24, 2023
• Actual Study Start Date: April 14, 2022
• Estimated Primary Completion Date: October 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 18, 2022)

Radiographic Progression-Free Survival (rPFS) Assessed by Investigator [ Time Frame: Randomization to radiographic progression or death from any cause (approximately 48 months) ]

rPFS Assessed by Investigator

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 18, 2022)

• rPFS Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Randomization to radiographic progression or death from any cause (approximately 48 months) ]
  rPFS Assessed by BICR
• Castration-resistant Prostate Cancer (CRPC)-free Survival [ Time Frame: Randomization to the earliest date of PSA or radiographic progression with a testosterone level of ≤50 nanogram/deciliter (ng/dL); or death from any cause (approximately 48 months) ]
  CRPC-free Survival
• Overall Survival (OS) [ Time Frame: Baseline to date of death due to any cause (approximately 60 months) ]
  OS
• Time to Pain Progression [ Time Frame: Randomization to pain progression (approximately 48 months) ]
  Measured by a combination of 2 scales, the Brief Pain Inventory Short Form (BPI-SF) Worst Pain Numeric Rating Scale (NRS) and the Analgesic Quantification Algorithm (AQA) scale. The BPI-SF Worst Pain NRS is a self-reported 11-item questionnaire on worst pain intensity on the past 24 hours. Score ranges from 0 (no pain) to 10 (pain as bad as you can imagine). The AQA scores analgesic use from 0 (minimum) to 7 (maximum).
• Time to Deterioration in Health-Related Quality of Life (HRQoL) [ Time Frame: Randomization to the date of HRQoL deterioration (approximately 48 Months) ]
  Measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P; Physical well-being and Prostate Cancer Subscale). The FACT-P is a 39-item self-reported questionnaire that assesses physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items are scored from 0 (not at all) to 4 (very much). The total FACT-P score ranges from 0-156, with higher scores representing a better quality of life.
• Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib [ Time Frame: Postdose Cycle 1 Day 1 through Predose Cycle 3 Day 1 (28 Day Cycles) ]
  PK: Mean steady state exposure of abemaciclib

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Abemaciclib (LY2835219) With Abiraterone in Men With Prostate Cancer That Has Spread to Other Parts of the Body and is Expected to Respond to Hormonal Treatment (Metastatic Hormone-Sensitive Prostate Cancer)
• Official Title: CYCLONE 3: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Abemaciclib in Combination With Abiraterone Plus Prednisone in Men With High-Risk Metastatic Hormone-Sensitive Prostate Cancer
• Brief Summary: The purpose of this study is to learn whether adding abemaciclib to abiraterone plus prednisone prolongs the time before prostate cancer gets worse. Participation may last approximately 60 months.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Prostatic Neoplasms
• Neoplasm Metastasis
• Urogenital Neoplasms
• Physiological Effects of Drugs
• Antineoplastic Agents
• Antineoplastic Agents, Hormonal
• Androgens
• Hormones
• Hormones, Hormone Substitutes, and Hormone Antagonists
• Abiraterone Acetate
• Steroid Synthesis Inhibitors
• Cytochrome P-450
• Enzyme Inhibitors
• Prednisone
• Prednisolone
• Cyclin-Dependent Kinase 4
• Cyclin-Dependent Kinase 6

Intervention

• Drug: Abemaciclib
  Administered orally.
  Other Name: LY2835219
• Drug: Abiraterone
  Administered orally.
• Drug: Prednisone or Prednisolone
  Administered orally.
• Drug: Placebo for Abemaciclib
  Administered orally.

Study Arms

• Experimental: Abemaciclib + Abiraterone + Prednisone/Prednisolone
  Abemaciclib plus (+) abiraterone + prednisone/prednisolone administered orally.
  Interventions:

  • Drug: Abemaciclib
  • Drug: Abiraterone
  • Drug: Prednisone or Prednisolone
• Active Comparator: Placebo + Abiraterone + Prednisone/Prednisolone
  Placebo + abiraterone + prednisone/prednisolone administered orally.
  Interventions:

  • Drug: Abiraterone
  • Drug: Prednisone or Prednisolone
  • Drug: Placebo for Abemaciclib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 18, 2022): 900
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 1, 2027
• Estimated Primary Completion Date: October 1, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adenocarcinoma of the prostate (as the predominant histology)

• High-risk metastatic hormone-sensitive prostate cancer. High risk is defined as:

  • Greater than or equal to (≥)4 bone metastases by bone scan and/or
  • ≥1 visceral metastases by computed tomography or magnetic resonance imaging
• Must have initiated androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist or bilateral orchiectomy prior to randomization. Up to 3 months of ADT prior to randomization is permitted with or without first-generation anti-androgen.
• Adequate organ function
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• Prior treatment with abemaciclib or any other cyclin dependent kinase 4 and 6 (CDK4 & 6) inhibitor
• Development of metastatic prostate cancer in the context of castrate levels of testosterone
• Received any prior systemic therapy for metastatic prostate cancer (including investigational agents), except for ADT and first-generation anti-androgen
• Clinically significant cardiovascular disease as evidenced by myocardial infarction, arterial thrombotic events, or severe/unstable angina in the past 6 months, or New York Heart Association Class II to IV heart failure
• History of syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin, or sudden cardiac arrest. Chronic and hemodynamically stable atrial arrhythmia well-controlled on medical therapy is permitted
• Uncontrolled hypertension
• Clinically active or chronic liver disease, moderate/severe hepatic impairment
• Known untreated central nervous system (CNS) metastasis. Participants with a history of treated brain metastases are eligible if stable for at least 8 weeks prior to randomization and off corticosteroid for at least 2 weeks prior to randomization

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 1-317-615-4559; ClinicalTrials.gov@lilly.com

• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Spain, Taiwan, Turkey, United Kingdom, United States
• Removed Location Countries: Russian Federation

Administrative Information

• NCT Number: NCT05288166
• Other Study ID Numbers: 18448; I3Y-MC-JPEG ( Other Identifier: Eli Lilly and Company ); 2022-500461-28-06 ( Other Identifier: EU Trial Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: 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); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: May 7, 2023