Clinical Trials /

Abemaciclib With or Without Atezolizumab in Metastatic Castration Resistant Prostate Cancer

NCT04272645

Description:

This research is studying two experimental drugs, abemaciclib and atezolizumab, alone and in combination with each other, to learn about the safety and effectiveness of these treatments and their side effects. This is an investigational study treatment for adult men with metastatic castrate resistant prostate cancer (mCRPC) who have progressive disease despite previous treatment with androgen deprivation therapy (ADT). One group of men (men without a genetic mutation called "CDK12 loss") will receive abemaciclib therapy alone. Two other groups of men (men with CDK12 loss in one group and men without CDK12 loss in the other) will receive the combination of abemaciclib and atezolizumab. Another group of men with CDK12 loss will receive atezolizumab therapy alone.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abemaciclib With or Without Atezolizumab in Metastatic Castration Resistant Prostate Cancer
  • Official Title: A Phase II Multi-Center Trial of Abemaciclib With or Without Atezolizumab in Metastatic Castration Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2019.124
  • SECONDARY ID: HUM00171336
  • NCT ID: NCT04272645

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
Abemaciclib 200 MGArm A - Abemaciclib 200 mg
Atezolizumab 1200 MG in 20 ML InjectionArm B - Abemaciclib 150 mg + atezolizumab
Abemaciclib 150 MGArm B - Abemaciclib 150 mg + atezolizumab

Purpose

This research is studying two experimental drugs, abemaciclib and atezolizumab, alone and in combination with each other, to learn about the safety and effectiveness of these treatments and their side effects. This is an investigational study treatment for adult men with metastatic castrate resistant prostate cancer (mCRPC) who have progressive disease despite previous treatment with androgen deprivation therapy (ADT). One group of men (men without a genetic mutation called "CDK12 loss") will receive abemaciclib therapy alone. Two other groups of men (men with CDK12 loss in one group and men without CDK12 loss in the other) will receive the combination of abemaciclib and atezolizumab. Another group of men with CDK12 loss will receive atezolizumab therapy alone.

Trial Arms

NameTypeDescriptionInterventions
Arm A - Abemaciclib 200 mgExperimentalAbemaciclib twice daily. 1 cycle of treatment is 21 days in length.
  • Abemaciclib 200 MG
Arm B - Abemaciclib 150 mg + atezolizumabExperimentalAtezolizumab on the first day of each 21-day cycle in combination with abemaciclib twice daily.
  • Atezolizumab 1200 MG in 20 ML Injection
  • Abemaciclib 150 MG
Experimental: Arm C - Patients with CDK12 lossExperimentalGroup 1 - Atezolizumab: Patients with CDK12 loss will receive atezolizumab monotherapy on the first day of each 21-day cycle Group 2 - Abemaciclib 150 mg + atezolizumab: Patients with CDK12 loss will receive atezolizumab on the first day of each 21-day cycle in combination with abemaciclib twice daily.
  • Atezolizumab 1200 MG in 20 ML Injection
  • Abemaciclib 150 MG

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of metastatic castration resistant prostate cancer (mCRPC), with histologic
             confirmation of adenocarcinoma of the prostate, without evidence of small cell
             carcinoma.

          -  ECOG performance status of 0 or 1.

          -  Evaluable for response based on: baseline PSA ≥ 2 ng/mL OR measurable disease per
             RECIST 1.1 criteria.

          -  Past progression or intolerance to at least one novel antiandrogen therapy
             (abiraterone, enzalutamide, galeterone, apalutamide, darolutamide, orteronel,
             seviteronel or equivalent) in either the hormone-sensitive or castration-resistant
             disease setting.

          -  Not a candidate for docetaxel or cabazitaxel chemotherapy due to: progression within
             12 months of completion or intolerance to prior taxane OR refusal of taxane OR
             contraindication to, or lack of fitness for taxane OR Investigator assessment that
             taxane is not clinically indicated or preferred.

          -  Maintenance of castration status, defined as serum testosterone level of less than 50
             ng/dL. Patients must be surgically castrate or maintained on LHRH agonist or
             antagonist therapy for the duration of the study period.

          -  Must have recovered from any treatment-related toxicities to ≤ CTCAE grade 1. Patients
             with ≤ CTCAE grade 2 anorexia, alopecia, neuropathy, and/or fatigue however, are also
             permitted to enroll.

          -  Adequate bone marrow, renal, and liver function with no lab abnormalities > CTCAE
             grade 1. Platelet count of ≥100 x 109 /L.

          -  Life expectancy of at least 6 months, as determined by a study Investigator.

          -  Ability to swallow oral medications.

          -  Ability to understand and willingness to sign an IRB-approved informed consent.

        For inclusion specifically in Arm C, documentation (via CLIA approved, CAP certified next
        generation sequencing [NGS] assay report) of genomic aberration resulting in CDK12 loss of
        function in metastatic tumor tissue.

        Exclusion Criteria:

          -  Clinical evidence of, or known and untreated metastatic CNS disease.

          -  Concurrent active malignancy. Patients with non-melanomatous skin cancer, cancer not
             needing active therapy for at least 2 years, cancer for which the treating
             investigator deems the subject to be in remission, or any prior malignancy that was
             treated with curative intent (no evidence of disease for at least 3 years) are also
             permitted to enroll.

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to planned cycle 1 day 1 of study treatment.

          -  Patients who have received oral anti-neoplastic intervention such as an oral hormonal
             agent, PARP inhibitor, AR targeted therapy, or oral experimental agent within 14 days
             prior to planned cycle 1 day 1 of study treatment.

          -  Prior treatment with an inhibitor of CDK4 and/or 6.

          -  Prior treatment with an inhibitor of PD-1, PD-L1, or PD-L2.

          -  Patients on concurrent therapy with a moderate or strong CYP3A4 inducer or inhibitor
             which cannot be safely stopped at least five half-lives prior to initiation of therapy
             with abemaciclib.

          -  Evidence of an active autoimmune disease that has required systemic treatment within
             the last 2 years (i.e. with use of disease modifying agents, corticosteroids or
             immunosuppressive drugs). Patients with conditions requiring replacement therapy
             (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for
             adrenal or pituitary insufficiency, etc.) are permitted to enroll.

          -  Live vaccine within 30 days of registration.

          -  Evidence of active, non-infectious pneumonitis. Patients with a history of
             asymptomatic radiation pneumonitis with no signs of active process are permitted to
             enroll.

          -  Active bacterial or fungal infection, or known detectable viral infection (e.g., Human
             Immunodeficiency Virus [HIV] or viral hepatitis).

          -  Arterial or venous thromboembolic event within the last 3 months.

          -  Significant infection, medical condition, or social situation which, in the opinion of
             the investigator, would preclude participation or limit the patient's ability to
             comply with study requirements.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS) (Arms A and B)
Time Frame:6 months after start of treatment
Safety Issue:
Description:Percentage of patients without disease progression at 6 months after start of treatment. Disease progression as defined by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria.

Secondary Outcome Measures

Measure:Objective response rate (ORR) (Arms A and B)
Time Frame:Up to 2 years after end of treatment or until study closes, whichever is earliest
Safety Issue:
Description:The percentage of patients with at least 50% decline in PSA from pretreatment baseline per PCWG3 criteria
Measure:Clinical benefit rate (CBR) (Arms A and B)
Time Frame:Up to 2 years after end of treatment or until study closes, whichever is earliest
Safety Issue:
Description:CBR as estimated by proportion of evaluable patients who had complete response (CR), partial response (PR) or stable disease (SD) as their best response to treatment by PCWG3 criteria.
Measure:Duration of response (DOR) (Arms A and B)
Time Frame:Up to 2 years after end of treatment or until study closes, whichever is earliest
Safety Issue:
Description:DOR among responders by PCWG3 criteria will be reported by treatment arm using Kaplan-Meier methods.
Measure:Duration of therapy (DOT) (Arms A and B)
Time Frame:Up to 2 years after end of treatment or until study closes, whichever is earliest
Safety Issue:
Description:DOT among responders by PCWG3 criteria will be reported by treatment arm using Kaplan-Meier methods.
Measure:Time to progression (TTP) (Arms A and B)
Time Frame:Up to 2 years after end of treatment or until study closes, whichever is earliest
Safety Issue:
Description:TTP among responders by PCWG3 criteria will be reported by treatment arm using Kaplan-Meier methods.
Measure:Number and severity of Adverse Events of Special Interest (AESI) (all arms)
Time Frame:Up to 2 years after end of treatment or until study closes, whichever is earliest
Safety Issue:
Description:Assessed by Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Results will be submitted in tabular format, showing the number of each AESI by grade (names of AESI in rows; grades 1 - 5 in columns). AESIs are protocol-specific (as defined in the protocol).
Measure:Overall survival among all patients (Arms A and B)
Time Frame:Up to 2 years after end of treatment or until study closes, whichever is earliest
Safety Issue:
Description:Number of patients (in arms A and B) alive at 2 years after the end of their treatment.
Measure:Overall survival among patients who respond to treatment (Arms A and B)
Time Frame:Up to 2 years after end of treatment or until study closes, whichever is earliest
Safety Issue:
Description:Number of patients who responded to treatment (per PCWG3 criteria) alive at 2 years after the end of their treatment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Last Updated

February 13, 2020