Abemaciclib in Combination With Androgen Deprivation Therapy for Locally Advanced Prostate Cancer

NCT04298983 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB-300004706I3Y-US-I001
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase II study is designed to study the clinical and radiologic response, as well as, safety and tolerability of abemaciclib in combination with androgen deprivation therapy (ADT) in patients with localized high-risk or locally advanced prostate cancer who are eligible for definitive radiation therapy (RT) and androgen deprivation therapy (ADT).

Conditions

Prostate Cancer

Keywords

abemaciclib; androgen deprivation therapy; radiation therapy

Outcome Measures

Primary Outcomes (1)

• Clinical Response Rates

  Clinical response rates will be assessed by percentage of patients who achieve the PSA nadir levels of \< 0.5ng/ml on treatment

  Baseline to 24 months

Secondary Outcomes (2)

• Number of Patients With PSA Declines Prior to Radiotherapy

  Up to 3 months of treatment

• Number of Patients to Experience PSA Failure

  Baseline up to 24 months

Study Arms (1)

Abemaciclib + ADT+ RT

EXPERIMENTAL

Abemaciclib at 150 mg by mouth twice daily, androgen deprivation therapy (ADT), and radiation therapy in conjunction with ADT.

Drug: Abemaciclib 150 MG by mouth twice daily; Drug: Androgen deprivation therapy (ADT); Radiation: Radiation Therapy

Interventions

Abemaciclib 150 MG by mouth twice daily DRUG

Abemaciclib will start with initiation of ADT, 3 months before RT, and pause 2 weeks prior to start of RT. Abemaciclib will resume with the first ADT administration post-radiation, which is about 1 month post radiation therapy. Abemaciclib will continue for a total of 24 months.

Abemaciclib + ADT+ RT

Androgen deprivation therapy (ADT) DRUG

ADT will be given every 3 months. ADT and Abemaciclib will pause 2 weeks prior to start of RT. ADT administration will resume with Abemaciclib post-radiation, which is about 1 month post radiation therapy. ADT will continue for a total of 24 months.

Abemaciclib + ADT+ RT

Radiation Therapy RADIATION

RT will start 3 months after initiation of ADT and Abemaciclib. RT will be given as standard of care- 180 cGy x 28 fractions to the whole pelvis and the prostate will receive 250 cGy x 28 fractions. After RT is completed, both ADT and Abemaciclib will resume and continue for 24 months.

Abemaciclib + ADT+ RT

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ECOG PS=0 or 1.
• Must have at least 1 target lesion.
• Adequate hematologic and end-organ function:
• ANC ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Hb ≥ 9g/dl
• Creatinine ≤ ULN or Creatinine Clearance (CrCl) ≥ 60 ml/min
• Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert syndrome, who can have total Bilirubin \> 2.0 x ULN and direct bilirubin within normal limits are permitted).

You may not qualify if:

• Prior treatment to CDK4-6 inhibitor.
• Prior treatment with systemic agents 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 for 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 judgment 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 \[e.g. estimated creatinine clearance \<30ml/min\], 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 PI.
• Patients with active autoimmune disease and history of inflammatory bowel disease. Brachytherapy boost will not be permitted.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

University of Alabama at Birmingham (UAB)

Birmingham, Alabama, 35249, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

abemaciclib; Androgen Antagonists; Radiotherapy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutics

Limitations and Caveats

A total of 9 patients were enrolled in the study. Two patients completed the entire protocol specified therapy. 4 patients were taken off study drug due to SAEs. The trial was terminated (along with the 3 remaining patients discontinuing drug) early due to negative results of a later phase clinical trial in men with metastatic prostate cancer. No longer proceeding with study.

Results Point of Contact

• Title: Andrew McDonald, MD; Principal Investigator
• Organization: University of Alabama at Birmingham (UAB)

ammcdonald@uabmc.edu

2059345670

Study Officials

• Andrew McDonald, MD

  University of Alabama at Birmingham (UAB)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 6, 2020
• Study Start: February 25, 2021
• Primary Completion: July 18, 2024
• Study Completion: September 4, 2024
• Last Updated: March 19, 2025
• Results First Posted: March 19, 2025

Record last verified: 2025-02

Locations

US (1)