A Study of Abiraterone Acetate Plus Prednisone with or without Abemaciclib in Patients with Metastatic Castration-Resistant Prostate Cancer
- Conditions
- Metastatic Castration-Resistant Prostate CancerMedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004276-21-GB
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 180
[1] Male patients, 18 years of age or greater; willing and able to provide written informed consent.
[2] Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology.
[3] Metastatic prostate cancer documented by positive bone scan and/or measurable soft tissue metastatic lesions by computed tomography (CT) or magnetic resonance imaging (MRI). If lymph node metastasis is the only evidence of metastasis, it must be =1.5cm in the short axis. Visceral metastasis, including to liver, is allowed.
[4] Serum testosterone level = 1.73 nmol/L (50 ng/dL) at the Screening visit. Patients who have not undergone orchiectomy are required to continue androgen-deprivation therapy (LHRH agonists/antagonists) throughout the study.
[5] Progressive disease at study entry demonstrated during continuous androgen deprivation therapy (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 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 RECIST1.1 for soft tissue and/or per PCWG3 for bone, with or without PSA progression.
[6] Patient must have discontinued all previous treatments for cancer (except androgen-deprivation therapy 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 4.0) 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.
[7] Must be able and willing to undergo mandatory tumor biopsy of at least one metastatic site which will be collected following determination of eligibility and before initiating study treatment.
[8] Have adequate organ function.
[9] Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
[10] Willing to comply with study procedures, able to swallow large capsules. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
[11] Prior therapy with CYP17 inhibitors (including abiraterone acetate, TAK-700, TOK-001 and ketoconazole)
[12] Prior treatment with abemaciclib or any CDK4 & 6 inhibitors
[13] Known or suspected contraindications or hypersensitivity to abiraterone acetate, prednisone or abemaciclib or to any of the excipients.
[14] 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, sipuleucel-T. Patients who had prior radiation or surgery to all target lesions.
[15] 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 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 longer) 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 Lilly clinical research physician (CRP) is required to establish eligibility.
[16] Gastrointestinal disorder affecting absorption or inability to swallow large pills
[17] 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, as judged by the Lilly CRP, are eligible for this study. The Lilly CRP will approve enrollment of patients with prior malignancies in remission before these patients are enrolled.
[18] The patient has 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).
[19] The patient has an 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 therapy.
[20] Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart failure or cardiac ejection fraction measurement of < 50% at baseline.
[21] 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.
[22] History of adrenal dysfunction
[23] The patient has active bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral inf
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method