Ensayos clínicos

Inclusion Criteria: 

• Male patients, 18 years of age or older.
• Willing and able to provide written informed consent.
• 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).
• Serum testosterone level ≤ 1.73 nmol/L (50 ng/dL) at the screening visit. Patients who have not undergone bilateral orchiectomy are required to continue ADT (LHRH agonists/antagonists) throughout the study.
• Progressive disease at study entry demonstrated during continuous ADT/post orchiectomy defined as one or more of the following criteria:
  • Sequence of at least 2 rising PSA values at a minimum of 1-week intervals with the last result being at least 1.0 ng/mL if confirmed PSA rise is the only indication of progression. Patients who received an anti-androgen must have PSA progression after withdrawal (≥ 4 weeks since last flutamide or ≥ 6 weeks since last bicalutamide or nilutamide);
  • Radiographic progression per RECIST 1.1 for soft tissue and/or per PCWG3 for bone (i.e., appearance of ≥ 2 new bone lesions), with or without PSA progression.
• Patient must have discontinued all previous treatments for cancer (except ADT and bone loss-prevention treatment), must have recovered from of all acute toxic effects of prior therapy or surgical procedure to Grade ≤ 1 or baseline (as per Common Terminology Criteria for Adverse Events version 5.0 [CTCAE v 5.0]) prior to randomization, with the exception of alopecia or peripheral neuropathy AND have a washout period from last dose of prior systemic or radiation therapy as follows:
  • Patients must discontinue flutamide at least 4 weeks, bicalutamide and nilutamide at least 6 weeks, prior to randomization;
  • At least 4 weeks must have elapsed from the use of 5-α reductase inhibitors (e.g., dutasteride, finasteride), estrogens, and cyproterone to randomization;
  • At least 4 weeks must have elapsed from the use of chemotherapy (i.e., docetaxel, for mHSPC) to randomization;
  • At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization.
• Mandatory for Part 1 and Part 2; optional for Part 3: Able and willing to undergo tumor biopsy of at least 1 metastatic site, which should be collected following determination of eligibility and before initiating study treatment.
  • Biopsy of newly emerged radiographic metastases is desired and preferable to the biopsy of previously existing lesions whenever possible;
  • Soft-tissue as well as bony metastatic lesions will be considered acceptable. Softtissue biopsy is preferred to bone biopsy whenever possible;
  • Adequate archival metastatic tissue can be used if available in lieu of a new biopsy: if the biopsy was done within 12 weeks prior to randomization and no treatment was initiated from biopsy to study entry. Optional for Part 1, Part 2, and Part 3: Biopsy of metastatic tissue at the time of on-study radiographic progression, prior to start of new anti-cancer therapy.
    • Biopsy of a progressing metastatic lesion is preferred whenever possible;
    • If patient discontinues study for reasons other than radiographic progression, the biopsy should be considered only if the patient has completed at least 6 cycles of study treatment.
• Have adequate organ function.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• Willing to comply with study procedures. Patients with reproductive potential must agree to use effective contraception and to not donate sperm during the study and for at least 3 months following the last dose of study treatment.

Exclusion Criteria: 

• Prior therapy with cytochrome P450 (CYP)17 inhibitors. 
• Prior treatment with abemaciclib or any cyclin-dependent kinase (CDK) 4 & 6 inhibitors. 
• Known or suspected contraindications or hypersensitivity to abiraterone acetate, prednisone, or abemaciclib or to any of the excipients.
• Prior cytotoxic chemotherapy for metastatic castration resistant prostate cancer (patients treated with docetaxel in the mHSPC are eligible). Prior radiopharmaceuticals for prostate cancer, or prior enzalutamide, apalutamide, darolutamide, or sipuleucel-T. Patients who had prior radiation or surgery to all target lesions.
• Are currently enrolled 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. 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 Clinical Research Physician/Clinical Research Scientist (CRP/CRS) is required to establish eligibility.
• Gastrointestinal disorder affecting the absorption or ability to swallow large pills. 
• Have prior malignancies 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 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.
• The patient has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (e.g., 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).
• The patient has a 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. Atrial fibrillation or other cardiac arrhythmia requiring medical therapy.
• Clinically significant heart disease as evidenced by myocardial infarction, arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II to IV heart failure or cardiac ejection fraction measurement of < 50% at baseline.
• Patients with 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.
• The patient has 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.
• Known or suspected central nervous system (CNS) metastatic disease (baseline screening for CNS metastases is not required unless there is presence of signs and/or symptoms of involvement).
• 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.
• Life expectancy < 6 months. [
• Patient treated with drugs known to be strong inhibitors or strong or moderate inducers of cytochrome P450 3A4 (CYP3A4) and the treatment cannot be discontinued or switched to a different medication at least 5 half-lives prior to starting study drug.
• Have received recent (within 4 weeks prior to randomization) live vaccination. Seasonal flu vaccines that do not contain a live virus are permitted.
• Untreated spinal cord compression or evidence of spinal metastases with risk of spinal compression. Structurally unstable bone lesions suggesting impending fracture.

Eligibility last updated 9/29/21. Questions regarding updates should be directed to the study team contact.