Abemaciclib in Combination With Androgen Deprivation Therapy for Locally Advanced Prostate Cancer (RAD 1805)
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|ClinicalTrials.gov Identifier: NCT04298983|
Recruitment Status : Recruiting
First Posted : March 6, 2020
Last Update Posted : April 27, 2021
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: Abemaciclib 150 MG by mouth twice daily Drug: Androgen deprivation therapy (ADT) Radiation: Radiation Therapy||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Clinical Trial of Abemaciclib in Combination With Androgen Deprivation Therapy for Locally Advanced Prostate Cancer|
|Actual Study Start Date :||February 25, 2021|
|Estimated Primary Completion Date :||April 2023|
|Estimated Study Completion Date :||April 2024|
Experimental: Abemaciclib + ADT+ RT
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
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.
Drug: 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.
Radiation: Radiation Therapy
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.
- 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
- PSA declines prior to radiotherapy [ Time Frame: Up to 3 months of treatment ]PSA declines prior to radiotherapy- calculated from nadir level prior to initiation of radiation therapy
- Time to PSA Failure [ Time Frame: Baseline up to 24 months ]Time to PSA failure will be analyzed using the Kaplan-Meier method
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04298983
|Contact: Eddy Yang, MD, PhD||(205) firstname.lastname@example.org|
|United States, Alabama|
|University of Alabama at Birmingham (UAB)||Recruiting|
|Birmingham, Alabama, United States, 35249|
|Contact: Eddy Yang, MD, PhD email@example.com|
|Principal Investigator:||Eddy Yang, MD, PhD||University of Alabama at Birmingham (UAB)|