Abemaciclib (LY2835219) in Men With Heavily Treated Metastatic Castration-Resistant Prostate Cancer (CYCLONE 1)

• ClinicalTrials.gov Identifier: NCT04408924
• Recruitment Status: Active, not recruiting
• First Posted: May 29, 2020
• Results First Posted: May 24, 2023
• Last Update Posted: May 24, 2023
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The study will evaluate how safe and effective abemaciclib is when given to participants whose metastatic prostate cancer progresses after they had received several previous treatments.

Condition or disease	Intervention/treatment	Phase
Metastatic Castration-Resistant Prostate Cancer	Drug: Abemaciclib	Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: CYCLONE 1: A Phase 2 Study of Abemaciclib in Metastatic Castration-Resistant Prostate Cancer Patients Previously Treated With a Novel Hormonal Agent and Taxane-based Chemotherapy
• Actual Study Start Date: January 20, 2021
• Actual Primary Completion Date: April 27, 2022
• Estimated Study Completion Date: August 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: 200 milligram (mg) Abemaciclib Twice Daily; Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.	Drug: Abemaciclib; Administered orally; Other Name: LY2835219

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Confirmed Objective Response (Objective Response Rate [ORR]) [ Time Frame: From Date of First Dose until Objective Progression (Up To 12.8 Months) ]

   ORR is defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) in soft tissue per response evaluation criteria in solid tumors (RECIST) version 1.1 and do not have concurrent bone progression per Prostate Cancer Clinical Trials Working Group 3 (PCWG3), as assessed by the investigator.

   ORR = (participants with confirmed CR and no bone progression) + (participants with confirmed PR and no bone progression) x 100 / all treated participants.

Secondary Outcome Measures :

1. Radiographic Progression-Free Survival (rPFS) [ Time Frame: From Date of First Dose until Objective Progression or Death from Any Cause (Up To 12.8 Months) ]
   The rPFS time is measured from the date of first dose to the earliest date of investigator-assessed radiographic progression per RECIST 1.1 for soft tissue and PCWG3 criteria for bone, or death from any cause, whichever occurred first. Participants who have neither progressed nor died will be censored at the day of their last radiographic tumor assessment (if available) or date of first dose if no post initiation (i.e., postbaseline) radiographic assessment is available.
2. Overall Survival (OS) [ Time Frame: From Date of First Dose until Date of Death from Any Cause (Estimated Up To 28 Months) ]
   OS time is measured from the date of first dose to the date of death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data were censored on the last date the participant was known to be alive.
3. Duration of Response (DoR) [ Time Frame: CR or PR to Disease Progression or Death Due to Any Cause (Estimated Up to 28 Months) ]
   DoR is measured only for confirmed responders (participants with a confirmed soft tissue best overall response of CR or PR per RECIST 1.1 no concurrent bone progression per PCWG3. It is measured from the date of first evidence of soft tissue CR or PR to the earliest date of investigator-assessed radiographic progression or death from any cause, whichever is earlier.
4. Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR]) [ Time Frame: From Date of First Dose until Measured Progressive Disease or Death Due to Any Cause (Up To 12.8 Months) ]
   The DCR is defined as the percentage of participants with confirmed soft tissue best overall response of CR, PR, or stable disease (SD) per RECIST 1.1, and do not have concurrent bone disease progression per PCWG3.
5. Time to Prostate-Specific Antigen (PSA) Progression [ Time Frame: From Date of First Dose until Confirmed PSA Progression (Up To 12.8 Months) ]
   Time to PSA progression is defined as the time from the date of treatment initiation to the date of first observation of PSA progression. The PSA progression is defined as a greater than or equal to (>=) 25 percentage (%) increase and an absolute increase of >=2 nanogram/milliliter (ng/mL) above the nadir (or baseline value if baseline is the smallest on study), which is confirmed by a second value obtained 3 or more weeks later.
6. Percentage of Participants Who Achieved Prostate-Specific Antigen (PSA) Response (PSA Response Rate) [ Time Frame: From Date of First Dose until Confirmed PSA Progression (Up To 12.8 Months) ]
   The PSA response rate is defined as the percentage of participants with a reduction in PSA level ≥50% from baseline, confirmed with a second assessment conducted at least 3 weeks later.
7. Time to Symptomatic Progression [ Time Frame: From Date of First Dose until Symptomatic Progression (Up to 12.8 Months) ]
   Time to symptomatic progression is defined as the time from first dose to any of the following (whichever occurred earlier): 1) symptomatic skeletal event, defined as symptomatic fracture, surgery, or radiation to bone, or spinal cord compression; 2) pain progression or worsening of disease-related symptoms requiring initiation of a new systemic anticancer therapy; and 3) development of clinically significant symptoms due to locoregional tumor progression requiring surgical intervention or radiation therapy. For participants who were not known to have symptomatic progression at the time of data analysis, data were censored on the last date at which no symptomatic progression was indicated.
8. Pharmacokinetics (PK): Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib [ Time Frame: Cycle (C) 1 Day (D) 1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose ]
   PK: Cmax,ss of abemaciclib is reported.
9. PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib [ Time Frame: C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose ]
   PK: Cmin,ss of abemaciclib is reported.
10. PK: Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib Metabolites (Total Active Species) [ Time Frame: C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose ]
    PK: Cmax,ss of abemaciclib metabolites (Total Active Species) is reported.
11. PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib Metabolites (Total Active Species) [ Time Frame: C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose ]
    PK: Cmin,ss of abemaciclib metabolites (Total Active Species) is reported.
12. Baseline Ki-67 Expression by Immunohistochemistry (IHC) [ Time Frame: Baseline ]

    Percentage of participants with expression of Ki-67 proliferation marker at baseline by immunohistochemistry.

    Baseline expression of the Ki-67 proliferation marker was evaluated by IHC utilizing a 20% or higher score to define high Ki-67 expression. The percentage of Ki-67 positive cells was defined by the number of non-apoptotic tumor cells with unequivocal brown nuclear staining (intensities ≥1 using a 0-3 scale) over the total number of non-apoptotic tumor cells. Unit of Measure is percentage of participants with low or high baseline Ki-67 expression.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Participant must have metastatic prostate cancer for which castration (medical or surgical) is no longer effective (castration-resistant).
• Participant must have disease spread to soft tissue that is measurable.
• Participant must have documented evidence of progressive disease by PSA test or imaging.
• Participant must have previously received at least one of the following treatment: abiraterone acetate, apalutamide, darolutamide or enzalutamide.
• Participant must have previously received chemotherapy with docetaxel and cabazitaxel.
• Participant must be willing and amenable to undergo a biopsy of tumor tissue (or able to provide adequate archived tumor tissue sample) and to provide blood for research.
• Participant must have good physical functioning ability and adequate organ function.

Exclusion Criteria:

• Participant must not have received more than 3 therapy regimens for metastatic castration-resistant prostate cancer (NOTE: GnRHa, first-generation antiandrogens (flutamide, nilutamide, or bicalutamide), diethylstilbestrol (DES) (or other estrogens), corticosteroids, ketoconazole, and bone loss-prevention will not count as systemic therapy regimens.
• Participants must not have previously received abemaciclib or any cyclin-dependent kinase (CDK)4 and/or CDK6 inhibitors.
• Participants must not have serious and/or uncontrolled preexisting medical condition(s) including but not limited to severe renal impairment, severe hepatic impairment, interstitial lung disease (ILD)/pneumonitis, severe dyspnea at rest or requiring oxygen therapy or other serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
• Participants must not have, or suspected to have, brain metastasis.
• Participants must not have untreated spinal cord compression, evidence of spinal metastases with risk of spinal compression or structurally unstable bone lesions suggesting impending fracture.

Contacts and Locations

Locations

United States, Utah

University of Utah - Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

United States, Washington

Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109

France

Centre Leon Berard

Lyon Cedex 08, France, 69373

Institut Paoli-Calmettes

Marseille, France, 13273

Hopital Europeen Georges Pompidou

Paris, France, 75015

Institut Claudius Regaud

Toulouse cedex 9, France, 31059

Gustave Roussy

Villejuif Cedex, France, 94805

Spain

Institut Catala d'Oncologia

L'Hospitalet de Llobregat, Barcelona, Spain, 08907

Corporacion Sanitaria Parc Tauli

Sabadell, Barcelona, Spain, 08208

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain, 08025

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

Hospital General Universitario Gregorio Maranon

Madrid, Spain, 28007

Hospital Universitario Ramon y Cajal

Madrid, Spain, 28034

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Sponsors and Collaborators

Eli Lilly and Company

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

  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:

Study Protocol  [PDF] March 4, 2021

Statistical Analysis Plan  [PDF] December 10, 2020

More Information

Additional Information:

Abemaciclib (LY2835219) in Men With Heavily Treated Metastatic Castration-Resistant Prostate Cancer (CYCLONE 1) 

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT04408924
• Other Study ID Numbers: 17583; I3Y-MC-JPCY ( Other Identifier: Eli Lilly and Company ); 2020-000290-24 ( EudraCT Number )
• First Posted: May 29, 2020
• Results First Posted: May 24, 2023
• Last Update Posted: May 24, 2023
• Last Verified: April 1, 2023

Individual Participant Data (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; Statistical Analysis Plan (SAP); 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/

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

Keywords provided by Eli Lilly and Company:

mCRPC; CDK4; CDK6; CDK4/6; CDK4&6 inhibitor; CDK4/6 inhibitor; LY2835219; CYCLONE 1; CYCLONE1

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases