Prostate CancerPhase 2RAD 1805NCT04298983
Abemaciclib in Combination With Androgen Deprivation Therapy for Locally Advanced Prostate Cancer
A Phase 2 study testing Abemaciclib 150 MG by mouth twice daily, Androgen deprivation therapy (ADT) and Radiation Therapy in people with Prostate Cancer, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Abemaciclib 150 MG by mouth twice daily, Androgen deprivation therapy (ADT) and Radiation Therapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2021to 4 Sep 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
- AST, 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham (UAB)
Birmingham, Alabama, 35249
About this study
Official title: Phase II Clinical Trial of Abemaciclib in Combination With Androgen Deprivation Therapy for Locally Advanced Prostate Cancer
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).
Read the detailed description
A similar hormone-driven cancer akin to breast cancers is prostate cancer. These tumors are driven by androgen receptor signaling, and CDK4/6 has also been found to be a bona fide target pre-clinically for advanced prostate cancer cell models. Moreover, CDK4/6 inhibition can act as a radiation sensitizer through its effects on the DNA damage response and interactions with cell cycle pathway proteins. For example, it has been found that expression of DNA repair proteins can be regulated by E2F, a transcription factor necessary for the G1 to S phase transition. Also, cyclin D1 has been found to exert a direct role in DNA repair. Lastly, CDK4/6 inhibition has been found to modulate the DNA damage response. These data support the use of CDK4/6 inhibitors as a modulator of DNA damage to enhance sensitivity to radiation.
Given the role of CDK4/6 in tumor resistance to endocrine therapy, in activation of the DNA damage response, and in promoting radiation resistance, we hypothesize that the targeting of CDK4/6 with abemaciclib will enhance the cytotoxicity in combination with blockade of the androgen receptor pathway. Therefore, we propose a pilot phase II investigator initiated trial in patients with high-risk prostate cancer testing the tolerability and toxicity of abemaciclib in combination with ADT.
Patients will receive ADT for 2 years and will start 3 months before radiation therapy. Abemaciclib will start with initiation of ADT and pause 2 weeks prior to start of radiation therapy. Abemaciclib will resume with the first ADT administration post-radiation, which is about 1 month post radiation therapy. Abemaciclib and ADT will continue for a total ADT period of 24 months. Patients will receive study treatment until development of toxicity or disease progression on treatment or any reasons of withdrawal or a maximum of 24 months of therapy with ADT. Patients are seen every 4 weeks with laboratory evaluation. For toxicity or adverse events, patients will undergo labs, physical examination and grades of toxicities will be determined using NCI CTCAE version 4.03.
- Conditions
- Prostate Cancer
- Being tested
- Abemaciclib 150 MG by mouth twice daily, Androgen deprivation therapy (ADT), Radiation Therapy
- Keywords
- abemaciclib, androgen deprivation therapy, radiation therapy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abemaciclib 150 MG by mouth twice dailyDrug
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.
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.
Radiation TherapyRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| Abemaciclib + ADT+ RT | Experimental | Abemaciclib at 150 mg by mouth twice daily, androgen deprivation therapy (ADT), and radiation therapy in conjunction with ADT. Receives: Drug: Abemaciclib 150 MG by mouth twice daily; Drug: Androgen deprivation therapy (ADT); Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline to 24 months
Secondary outcomes (2)
Number of Patients With PSA Declines Prior to Radiotherapy
Number of patients with PSA declines prior to radiotherapy- calculated from nadir level prior to initiation of radiation therapy
Measured: Up to 3 months of treatment
Number of Patients to Experience PSA Failure
Number of patients to experience PSA failure will be analyzed using the Kaplan-Meier method
Measured: Baseline up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2020
- Study start25 Feb 2021
- Primary completion18 Jul 2024
- Study completion4 Sep 2024
Why it stopped: Abemaciclib efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Principal investigator, Andrew McDonald, University of Alabama at Birmingham
- Investigators
- Andrew McDonald, MD, Principal investigator, University of Alabama at Birmingham (UAB)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04298983
- Sponsor's protocol ID
- IRB-300004706
- Other IDs
- I3Y-US-I001
- Acronym
- RAD 1805
- Status last verified
- Feb 2025
- First submitted
- 2 Mar 2020
- Last updated
- 19 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Trial of Abemaciclib in Combination With Androgen Deprivation Therapy for Locally Advanced Prostate Cancer
- ClinicalTrials.gov ID
- NCT04298983
- Acronym / sponsor ID
- RAD 1805 / IRB-300004706
- Conditions
- Prostate Cancer
- Keywords
- abemaciclib, androgen deprivation therapy, radiation therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Abemaciclib efficacy
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- 25 Feb 2021 (actual)
- Primary completion
- 18 Jul 2024 (actual)
- Study completion
- 4 Sep 2024 (actual)
- First posted
- 6 Mar 2020 (actual)
- Results
- Posted 19 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
A similar hormone-driven cancer akin to breast cancers is prostate cancer. These tumors are driven by androgen receptor signaling, and CDK4/6 has also been found to be a bona fide target pre-clinically for advanced prostate cancer cell models. Moreover, CDK4/6 inhibition can act as a radiation sensitizer through its effects on the DNA damage response and interactions with cell cycle pathway proteins. For example, it has been found that expression of DNA repair proteins can be regulated by E2F, a transcription factor necessary for the G1 to S phase transition. Also, cyclin D1 has been found to exert a direct role in DNA repair. Lastly, CDK4/6 inhibition has been found to modulate the DNA damage response. These data support the use of CDK4/6 inhibitors as a modulator of DNA damage to enhance sensitivity to radiation.
Given the role of CDK4/6 in tumor resistance to endocrine therapy, in activation of the DNA damage response, and in promoting radiation resistance, we hypothesize that the targeting of CDK4/6 with abemaciclib will enhance the cytotoxicity in combination with blockade of the androgen receptor pathway. Therefore, we propose a pilot phase II investigator initiated trial in patients with high-risk prostate cancer testing the tolerability and toxicity of abemaciclib in combination with ADT.
Patients will receive ADT for 2 years and will start 3 months before radiation therapy. Abemaciclib will start with initiation of ADT and pause 2 weeks prior to start of radiation therapy. Abemaciclib will resume with the first ADT administration post-radiation, which is about 1 month post radiation therapy. Abemaciclib and ADT will continue for a total ADT period of 24 months. Patients will receive study treatment until development of toxicity or disease progression on treatment or any reasons of withdrawal or a maximum of 24 months of therapy with ADT. Patients are seen every 4 weeks with laboratory evaluation. For toxicity or adverse events, patients will undergo labs, physical examination and grades of toxicities will be determined using NCI CTCAE version 4.03.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Abemaciclib + ADT+ RT | Experimental | Drug: Abemaciclib 150 MG by mouth twice daily, Drug: Androgen deprivation therapy (ADT), Radiation: Radiation TherapyAbemaciclib at 150 mg by mouth twice daily, androgen deprivation therapy (ADT), and radiation therapy in conjunction with ADT. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histologically confirmed (core biopsy proven) adenocarcinoma of prostate, localized high-risk or locally advanced.
- One of the below:
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Abemaciclib 150 MG by mouth twice dailyAbemaciclib 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. | Drug | Abemaciclib + ADT+ RT |
| Androgen deprivation therapy (ADT)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. | Drug | Abemaciclib + ADT+ RT |
| Radiation TherapyRT 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. | Radiation | Abemaciclib + ADT+ RT |
Primary outcome
Clinical Response Rates
Time frame: Baseline to 24 months
Clinical response rates will be assessed by percentage of patients who achieve the PSA nadir levels of < 0.5ng/ml on treatment
2 secondary outcomes
Number of Patients With PSA Declines Prior to Radiotherapy
Time frame: Up to 3 months of treatment
Number of Patients to Experience PSA Failure
Time frame: Baseline up to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew McDonald, MD principal investigator
University of Alabama at Birmingham (UAB)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Abemaciclib 150 MG by mouth twice daily, Androgen deprivation therapy (ADT) and Radiation Therapy in people with Prostate Cancer, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Response Rates (time frame: Baseline to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2025.