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Abemaciclib and Androgen Deprivation Therapy for the Treatment of Localized High-Risk or Locally Advanced Prostate Cancer

Trial Status: Active

This phase II trial studies the effect of abemaciclib and androgen deprivation therapy in treating patients with prostate cancer that has not spread to other parts of the body (localized) and is high-risk, or has spread to nearby tissue or lymph nodes (locally advanced). Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Since prostate cancer is driven prominently by high testosterone levels, drugs used in androgen deprivation therapy, such as goserelin acetate and leuprolide acetate, act to reduce the levels of testosterone and thus slow the growth of prostate cancer. Abemaciclib may work with androgen deprivation therapy to control growth and spread of prostate cancer so as to make the patient’s tumor better receptive to radiation therapy and improve outcomes to radiation therapy.

Inclusion Criteria

  • Histologically confirmed (core biopsy proven) adenocarcinoma of prostate, localized high-risk or locally advanced
  • One of the below: * Gleason 7-8, any T-stage, and PSA > 20 * Gleason 8, >= T2, any PSA * Gleason 9-10, any T-stage, any PSA
  • Available biopsy of primary tumor or resected tumor specimen with adequate samples
  • Prior treatment with systemic anti-cancer agents is not allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 0 or 1
  • Must have at least 1 target lesion
  • Life expectancy > 6 months
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin (Hb) >= 9 g/dl
  • Creatinine =< upper limit of normal (ULN) or creatinine clearance (CrCl) >= 60 ml/min
  • Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin > 2.x ULN and direct bilirubin within normal limits are permitted)
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase =< ULN
  • Agreement to remain abstinent or use appropriate contraception
  • Willingness and ability to consent for self to participate in study
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria

  • Prior treatment with CDK 4/6 inhibitor
  • Prior treatment with systemic or radiation treatment for the primary cancer
  • Major surgical procedure or significant traumatic injury within 4 weeks prior to study treatment, and must have fully recovered from any such procedure
  • Personal 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
  • Angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack (TIA), arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) within 6 months prior to study treatment
  • Known active viral or non-viral hepatitis or cirrhosis
  • Any active infection requiring systemic treatment, positive tests for hepatitis B surface antigen or hepatitis C ribonucleic acid (RNA)
  • Known history of AIDS (acquired immunodeficiency syndrome)-defining illness
  • Patients must be surgically sterile or must agree to use effective contraception during the study treatment (including temporary breaks from treatment), and at least 180 days after stopping last dose of abemaciclib
  • Other severe and/or uncontrolled acute or chronic medical or psychiatric condition or laboratory abnormality that, in the judgement of the investigator, may increase the risk associated with study participation or may interfere with the interpretation of study results and would make the patient inappropriate for this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance < 30 ml/min], 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)
  • Secondary malignancy requiring active treatment. Past history of malignancy other than prostate cancer treated with curative intent and not requiring additional treatment may be eligible after discussion with principal investigator (PI)
  • Patients with active autoimmune disease and history of inflammatory bowel disease will be excluded. Brachytherapy boost will not be permitted

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: ACTIVE
Contact: Eddy Shih-Hsin Yang
Phone: 205-934-5670

PRIMARY OBJECTIVE:

I. To assess clinical response rates using proportion of patients with prostate-specific antigen (PSA) nadir of =< 0.5 ng/ml on treatment.

SECONDARY OBJECTIVES:

I. Proportion of patients with PSA declines prior to radiotherapy.

II. Time to PSA failure.

III. To study the tolerability and feasibility of combining abemaciclib with androgen deprivation therapy (ADT) for localized high risk or locally advanced prostate cancer.

EXPLORATORY OBJECTIVES:

I. Magnetic resonance imaging (MRI)-ultrasound (US) fusion imaging pre-treatment and at 6 months post radiation therapy (RT) with comparison with historical controls receiving RT + ADT.

II. Baseline (mandatory) and 6 months (optional) post RT tumor tissue profiling (MRI-US fusion guided) to identify association of molecular profile with PSA decline at 1 year.

III. Baseline, pre-radiotherapy and 6 months post-RT blood collection and profiling for molecular analysis.

OUTLINE:

Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28 (days 1-14 of cycle 3). Patients also receive goserelin acetate subcutaneously (SC), leuprolide acetate intramuscularly (IM) or SC, or other ADT luteinizing hormone-releasing hormone (LHRH) agents SC on day 1. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care RT. Beginning 1 month after completion of RT, patients receive abemaciclib PO BID on days 1-28. Patients also receive goserelin acetate SC, leuprolide acetate IM or SC, or other ADT LHRH agents SC on day 1. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for up to 12 months.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Alabama at Birmingham Cancer Center

Principal Investigator
Eddy Shih-Hsin Yang

  • Primary ID UAB1917
  • Secondary IDs NCI-2020-08418
  • Clinicaltrials.gov ID NCT04298983