A Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib (LY2835219) in Participants With Prostate Cancer (CYCLONE 2)

• ClinicalTrials.gov Identifier: NCT03706365
• Recruitment Status: Active, not recruiting
• First Posted: October 16, 2018
• Last Update Posted: April 18, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: September 18, 2018
• First Posted Date: October 16, 2018
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: November 26, 2018
• Actual Primary Completion Date: January 2, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 23, 2021)

Radiographic Progression Free Survival (rPFS) [ Time Frame: Baseline to Radiographic Disease Progression or Death from Any Cause (Estimated up to 21 Months) ]

rPFS by investigator assessment

Original Primary Outcome Measures (submitted: October 11, 2018)

• Radiographic Progression Free Survival (rPFS) [ Time Frame: Baseline to Radiographic Disease Progression or Death from Any Cause (Estimated up to 21 Months) ]
  rPFS
• Time to Prostate-Specific Antigen (PSA) Progression [ Time Frame: Baseline to the Date of the First Observation of PSA Progression (Estimated up to 21 Months) ]
  Time to PSA progression

Current Secondary Outcome Measures (submitted: July 23, 2021)

• Time to Prostate-Specific Antigen (PSA) Progression [ Time Frame: Baseline to the Date of the First Observation of PSA Progression (Estimated up to 21 Months) ]
  Time to PSA progression
• Radiographic Progression Free Survival (rPFS) [ Time Frame: Baseline to Radiographic Disease Progression or Death from Any Cause (Estimated up to 21 Months) ]
  rPFS by blinded, independent, central review
• Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline to Radiographic Disease Progression (Estimated up to 21 Months) ]
  ORR: Percentage of participants with a CR or PR
• Duration of Response (DOR) [ Time Frame: Date of First Documented CR or PR to Date of Radiographic Disease Progression or Death from Any Cause (Estimated up to 21 Months) ]
  DOR
• Overall Survival (OS) [ Time Frame: Baseline to Date of Death Due to Any Cause (Estimated up to 40 Months) ]
  OS
• Time to Symptomatic Progression [ Time Frame: Baseline to the Date of the First Documented Symptomatic Progression (Estimated up to 21 Months) ]
  Time to symptomatic progression
• Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib [ Time Frame: Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) ]
  PK: Mean steady state exposure of abemaciclib
• PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 [ Time Frame: Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) ]
  PK: Mean steady state exposure of abemaciclib metabolite LSN2839567
• PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 [ Time Frame: Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) ]
  PK: Mean steady state exposure of abemaciclib metabolite LSN3106726
• PK: Mean Steady State Exposure of Abiraterone Acetate [ Time Frame: Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) ]
  PK: Mean Steady State Exposure of Abiraterone Acetate
• Time to Worst Pain Progression [ Time Frame: Baseline through follow-up (Estimated up to 21 months) ]
  Measured by the Worst Pain Numeric Rating Scale (NRS) and World Health Organization-Analgesic Ladder (WHO-AL). NRS score measures worst pain over the last 24 hours on a 0 to 10-point NRS, where 0 -s "no pain" and 10 is "pain as bad as you can imagine. The WHO-AL classifies analgesic use into four categories, where 1 = no analgesic and 4 = strong opioids.

Original Secondary Outcome Measures (submitted: October 11, 2018)

• Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline to Radiographic Disease Progression (Estimated up to 21 Months) ]
  ORR: Percentage of participants with a CR or PR
• Duration of Response (DOR) [ Time Frame: Date of First Documented CR or PR to Date of Radiographic Disease Progression or Death from Any Cause (Estimated up to 21 Months) ]
  DOR
• Overall Survival (OS) [ Time Frame: Baseline to Date of Death Due to Any Cause (Estimated up to 40 Months) ]
  OS
• Time to Symptomatic Progression [ Time Frame: Baseline to the Date of the First Documented Symptomatic Progression (Estimated up to 21 Months) ]
  Time to symptomatic progression
• Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib [ Time Frame: Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) ]
  PK: Mean steady state exposure of abemaciclib
• PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 [ Time Frame: Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) ]
  PK: Mean steady state exposure of abemaciclib metabolite LSN2839567
• PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 [ Time Frame: Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) ]
  PK: Mean steady state exposure of abemaciclib metabolite LSN3106726
• PK: Mean Steady State Exposure of Abiraterone Acetate [ Time Frame: Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) ]
  PK: Mean Steady State Exposure of Abiraterone Acetate

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib (LY2835219) in Participants With Prostate Cancer
• Official Title: A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib in Patients With Metastatic Castration-Resistant Prostate Cancer
• Brief Summary: This study is being done to see how safe and effective abemaciclib is when given together with abiraterone acetate plus prednisone in participants with metastatic castration resistant prostate cancer. Prednisolone may be used instead of prednisone per local regulation.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

• Drug: Abemaciclib
  Administered orally.
  Other Name: LY2835219
• Drug: Abiraterone Acetate
  Administered orally.
• Drug: Prednisone
  Administered orally.
• Drug: Placebo
  Administered orally.

Study Arms

• Experimental: A1. Abiraterone plus Prednisone and Abemaciclib
  Abiraterone plus prednisone administered orally and abemaciclib administered orally.
  Interventions:

  • Drug: Abemaciclib
  • Drug: Abiraterone Acetate
  • Drug: Prednisone
• Experimental: A2. Abiraterone plus Prednisone and Abemaciclib
  Abiraterone plus prednisone administered orally and abemaciclib administered orally.
  Interventions:

  • Drug: Abemaciclib
  • Drug: Abiraterone Acetate
  • Drug: Prednisone
• Active Comparator: B1. Abiraterone plus Prednisone and Placebo
  Abiraterone plus prednisone administered orally and placebo administered orally.
  Interventions:

  • Drug: Abiraterone Acetate
  • Drug: Prednisone
  • Drug: Placebo
• Active Comparator: B2. Abiraterone plus Prednisone and Placebo
  Abiraterone plus prednisone administered orally and placebo administered orally.
  Interventions:

  • Drug: Abiraterone Acetate
  • Drug: Prednisone
  • Drug: Placebo
• Experimental: A. Abiraterone plus Prednisone and Abemaciclib
  Abiraterone plus prednisone administered orally and abemaciclib administered orally.
  Interventions:

  • Drug: Abemaciclib
  • Drug: Abiraterone Acetate
  • Drug: Prednisone
• Active Comparator: B. Abiraterone plus Prednisone and Placebo
  Abiraterone plus prednisone administered orally and placebo administered orally.
  Interventions:

  • Drug: Abiraterone Acetate
  • Drug: Prednisone
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 23, 2021): 350
• Original Estimated Enrollment (submitted: October 11, 2018): 180
• Estimated Study Completion Date: June 2026
• Actual Primary Completion Date: January 2, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate.
• Metastatic prostate cancer documented by positive bone scan and/or measurable soft tissue metastatic lesions by CT or magnetic resonance imaging (MRI).

• 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.

Exclusion Criteria:

• Prior therapy with cytochrome P450 (CYP)17 inhibitors.
• Prior treatment with abemaciclib or any cyclin-dependent kinase (CDK) 4 & 6 inhibitors.
• Prior cytotoxic chemotherapy for metastatic castration resistant prostate cancer (participants treated with docetaxel in the metastatic hormone-sensitive prostate cancer [mHSPC] are eligible). Prior radiopharmaceuticals for prostate cancer, or prior enzalutamide, apalutamide, darolutamide or sipuleucel-T. Participants who had prior radiation or surgery to all target lesions.
• Currently enrolled in a clinical study involving an investigational product.
• Gastrointestinal disorder affecting the absorption or ability to swallow large pills.
• Clinically significant heart disease, active or chronic liver disease, moderate/severe hepatic impairment (Child-Pugh Class B and C).

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, China, Denmark, France, Germany, Japan, Korea, Republic of, Netherlands, Romania, Spain, United States
• Removed Location Countries: Puerto Rico, United Kingdom

Administrative Information

• NCT Number: NCT03706365
• Other Study ID Numbers: 16598; I3Y-MC-JPCM ( Other Identifier: Eli Lilly and Company ); 2016-004276-21 ( EudraCT 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 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: April 2024