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

EU trial number: 2022-500461-28-06

Samenvatting

Dit is een gerandomiseerde fase III studie waarin het toevoegen van de CDK4/6 remmer abemaciclib aan upfront behandeling met abirateron in patiënten met gemetastaseerd hormoon-sensitief prostaatcarcinoom wordt onderzocht.

Inclusiecriteria

  •  Adult men (≥18 years or age of majority per local regulation) willing and able to provide written informed consent and comply with study procedures
  •  Histologically confirmed predominant adenocarcinoma of the prostate. Well-differentiated neuroendocrine carcinoma, small cell or large cell neuroendocrine carcinoma, sarcomatoid, and carcinoid tumors are excluded.
  • High-risk metastatic hormone-sensitive prostate cancer documented on conventional imaging. High-risk is defined as:
    • ≥4 bone metastases by bone scan and/or
    • ≥1 visceral metastases (for example, liver, lung, and adrenal) by CT or MRI.
  • Participants must have initiated ADT with 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 (for example, bicalutamide). The start of ADT is the earliest date an LHRH agonist/antagonist was administered, or date of surgical castration.
  • For participants receiving an LHRH agonist, first generation anti-androgens are allowed to continue for up to 2 weeks after Cycle 1 Day 1, all other use subsequent to Cycle 1 Day 1 is prohibited.
  • Participants who have not undergone a bilateral orchiectomy must continue the LHRH agonist/antagonist throughout the study.
  •  For patients receiving bone-modifying agents (for example, bisphosphonates or denosumab) for the management of bone metastasis, dose must be stable for at least 4 weeks prior to randomization. This does not apply to patients on osteoporosis dosing.
  • Have adequate organ function, as defined below:
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
  • Participants with female partners of childbearing potential must agree to use a condom along with another effective contraception method during the study and for at least 3 weeks following the last dose of study treatmen

Exclusiecriteria

  • Known or suspected contraindications or hypersensitivity to abiraterone, prednisone/prednisolone, or abemaciclib or to any of the excipients; inability to swallow oral medications or gastrointestinal disorder affecting absorption.
  • Prior treatment with abemaciclib or any other 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
  •  Adiation therapy to treat the primary prostate tumor in the context of metastatic disease and/or radiation or surgery to all metastatic lesions. One course of palliative radiation or surgical therapy is permitted if it was administered at least 2 weeks prior to randomization.
  •  Untreated spinal cord compression, spinal metastases with emergent risk of spinal cord compression, or structurally unstable bone lesions at high-risk for impending fracture.
  •  Known untreated CNS metastases or any history of leptomeningeal disease. Screening of asymptomatic patients for CNS metastases is not required. Note: Patients with a history of treated brain metastases by either surgery or radiation therapy are eligible provided that disease is stable following treatment for at least 8 weeks prior to randomization and with no requirement for corticosteroids for at least 2 weeks prior to randomization.
  •  Serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
  • 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 any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Chronic and hemodynamically stable atrial arrhythmia well-controlled on medical therapy is permitted.
  • Uncontrolled hypertension (systolic blood pressure [BP] ≥160 mmHg or diastolic BP ≥95 mmHg). Patients with a history of hypertension are allowed provided BP is controlled by anti-hypertensive treatment.
  • Clinically active or chronic liver disease, moderate/severe hepatic impairment (Child-Pugh Class B and C), ascites, or bleeding disorders secondary to hepatic dysfunction.
  • History of adrenal dysfunction.
  • Had a major surgery within 2 weeks prior to randomization. All incisions must be healed or healing, aseptic and without signs or symptoms of infection.
  • Prior or active concurrent malignancy (with the exception of non-melanomatous skin cancer). Patients with carcinoma in situ of any origin and patients with prior malignancies who are in remission and/or whose likelihood of recurrence is very low per investigator’s judgment are eligible for this study. The Lilly CRP/CRS will approve enrollment of patients with prior malignancies in remission before these patients are enrolled.
  • Active systemic infections (for example, bacterial infection requiring intravenous [IV] antibiotics at time of initiating study treatment, fungal infection, or detectable viral infection requiring systemic therapy) or viral load (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]). Screening is not required for enrollment.
  • Have received live vaccination ≤ 4 weeks prior to randomization. Inactivated vaccines are permitted.
  • Current enrollment in a clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study. Have participated in any clinical trial for which treatment assignment is still blinded. If patient has participated in a clinical study involving an investigational product, 3 months or 5 half-lives (whichever is shorter) should have passed prior to randomization. If a patient is currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the investigator and the Lilly CRP/CRS is required to establish eligibility.

Studiecoördinator

Dr. M. van Kruchten
Afdeling Medische Oncologie
Tel 050-3612821 (secretariaat Oncologie)
E-mail: m.van.kruchten@umcg.nl