Metastatic Castration-Resistant Prostate Cancer MedDRA 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)
Conditions
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: [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, (i.e., appearance of =2 new bone lesions), 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] Able and willing to undergo tumor biopsy of at least one metastatic site (mandatory for part 1 and 2, optional for part 3), which should 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 292 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 58
Exclusion criteria
Exclusion criteria: [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 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 Lilly Clinical Research Physician/Clinical Research Scientist (CRP/CRS) 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 per investigator's judgement 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 medical therapy. [20] 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-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 infection (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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To determine the RP2D of abemaciclib that may be safely administered to patients with mCRPC in combination with abiaterone acetate and prednisone. Part 1, 2 & 3: To compare the rPFS of patients receiving abiraterone acetate plus prednisone with or without abemaciclib. ;Secondary Objective: To characterize further the safety profile of the combination of abemaciclib and abiraterone acetate plus prednisone. To compare the efficacy in patients receiving abiraterone acetate plus prednisone with or without abemaciclib. Time to Symptomatic Progression. To characterize the PK of abemaciclib and abiraterone acetate when administered in combination. To assess patient reported pain ;Primary end point(s): Part 1: Safety (including but not limited to): TEAEs, SAEs, deaths, and clinical laboratory abnormalities Part 1, 2 & 3: rPFS;Timepoint(s) of evaluation of this end point: Safety evaluations will occur at each study visit. Radiologic assessment every 8 weeks for the first 24 weeks, every 12 weeks thereafter, and within 14 days of symptomatic progression if no radiographic progression yet. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The safety endpoints evaluated will include but are not limited to the following: AEs, TEAEs, SAEs, clinical laboratory tests, ECGs, vital signs, and physical examinations. • ORR and DoR • OS • Time to PSA progression • (If Part 3 is opened) rPFS by blinded, independent, central review (BICR) Time from randomization to any of the following (whichever occurs earlier): - Symptomatic Skeletal Event (SSE) - Pain progression or worsening of disease-related symptoms requiring initiation of a new systemic anti-cancer therapy - Development of clinically significant symptoms due to loco-regional tumor progression requiring surgical intervention or radiation therapy Abemaciclib and abiraterone acetate steady state plasma concentrations. Time to worst pain progression, using the Worst Pain NRS score and the WHO-AL. ;Timepoint(s) of evaluation of this end point: Safety evaluations will occur at each study visit. Radiologic assessment every 8 weeks for the first 24 weeks, every 12 weeks thereafter, and within 14 days of symptomatic progression if no radiographic progression yet. Worst pain NRS assessment will occur at baseline, on Day 1 of every cycle (every 4 weeks) and at every visit during post-treatment short-term follow up phase. | — |
Countries
Australia, Denmark, Germany, Korea, Republic of, Netherlands, Romania, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly
Outcome results
None listed