Abemaciclib With or Without Atezolizumab in Metastatic Castration Resistant Prostate Cancer

NCT04272645 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: UMCC 2019.124HUM00171336
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Progression free survival (PFS) (Arms A and B)

  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.

  6 months after start of treatment

• Incidence of dose limiting toxicities (DLTs) of combination therapy with abemaciclib and atezolizumab

  Dose safety for the combination of abemaciclib and atezolizumab is the DLT incidence in Arm B and the combination-therapy cohort of Arm C. DLT is defined in the protocol.

  From start of treatment to end of cycle 1; up to 21 days

Secondary Outcomes (8)

• Objective response rate (ORR) (Arms A and B)

  Up to 2 years after end of treatment or until study closes, whichever is earliest

• Clinical benefit rate (CBR) (Arms A and B)

  Up to 2 years after end of treatment or until study closes, whichever is earliest

• Duration of response (DOR) (Arms A and B)

  Up to 2 years after end of treatment or until study closes, whichever is earliest

• Duration of therapy (DOT) (Arms A and B)

  Up to 2 years after end of treatment or until study closes, whichever is earliest

• Time to progression (TTP) (Arms A and B)

  Up to 2 years after end of treatment or until study closes, whichever is earliest

Study Arms (3)

Arm A - Abemaciclib 200 mg

EXPERIMENTAL

Abemaciclib twice daily. 1 cycle of treatment is 21 days in length.

Drug: Abemaciclib 200 MG

Arm B - Abemaciclib 150 mg + atezolizumab

EXPERIMENTAL

Atezolizumab on the first day of each 21-day cycle in combination with abemaciclib twice daily.

Drug: Atezolizumab 1200 MG in 20 ML Injection; Drug: Abemaciclib 150 MG

Experimental: Arm C - Patients with CDK12 loss

EXPERIMENTAL

Group 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.

Drug: Atezolizumab 1200 MG in 20 ML Injection; Drug: Abemaciclib 150 MG

Interventions

Abemaciclib 200 MG DRUG

200 MG orally BID Days 1-21

Arm A - Abemaciclib 200 mg

Atezolizumab 1200 MG in 20 ML Injection DRUG

1200 mg IV on Day 1 of 21-day cycle

Arm B - Abemaciclib 150 mg + atezolizumab; Experimental: Arm C - Patients with CDK12 loss

Abemaciclib 150 MG DRUG

150 MG orally BID Days 1-21

Arm B - Abemaciclib 150 mg + atezolizumab; Experimental: Arm C - Patients with CDK12 loss

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (4)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University - St. Louis

St Louis, Missouri, 63130, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

abemaciclib; atezolizumab; Injections

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)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Ajjai Alva, MD

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: February 17, 2020
• Study Start: October 1, 2020
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: July 15, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)