Neoadjuvant Atezolizumab-Based Combination Therapy in Men With Localized Prostate Cancer Prior to Radical Prostatectomy

NCT03821246 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 18702NCI-2018-02805
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well atezolizumab works alone or in combination with etrumadenant or tocilizumab in treating men with localized prostate cancer before radical prostatectomy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Androgens can cause the growth of prostate cancer cells. IL-6 is expressed by prostate cancer and within the tumor microenvironment and shown to enhance prostate cancer and disease progression. Treatment with an anti-IL-6 antibody such as tocilizumab may inhibit cancer progression. Giving atezolizumab in combination with etrumadenant or tocilizumab may work better in treating prostate cancer.

Conditions

Prostate Adenocarcinoma; Prostate Cancer; Localized Prostate Cancer

Keywords

Neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects who demonstrate a positive response to neoadjuvant atezolizumab and atezolizumab-based combination therapy for each Cohort of the study

  A positive response is defined as a ≥40% increase in the number of infiltrating cluster of differentiation 3 (CD3) + T cells between the pre-treatment biopsy at baseline and the post-treatment RP specimen. Thus, a negative response is a \<40% increase. The primary endpoint will include all enrolled subjects who receive at least 1 dose of study treatment and undergo RP. Analysis of the primary endpoint will be performed for each cohort independently

  Up to 12 months

Secondary Outcomes (5)

• Number of treatment-related of adverse events

  Up to 12 months

• Sum of Pathologic complete response (pCR) and Minimal residual disease (MRD) rate

  Up to 12 months

• Rate of Pathologic complete response (pCR) rate

  Up to 12 months

• Rate of Minimal residual disease (MRD)

  Up to 12 months

• Prostate specific antigen (PSA) response

  Up to 12 months

Study Arms (3)

Cohort A (atezolizumab monotherapy)

EXPERIMENTAL

Participants receive one (1) cycle of atezolizumab, 1200mg intravenously (IV) over 30-60 minutes on day 1 of a 14 day cycle. Radical Prostatectomy (RP) will occur 21 days (+/- 7 days) following the final dose of atezolizumab. No further study therapy will be administered following RP.

Drug: Atezolizumab

Cohort B (atezolizumab, etrumadenant)

EXPERIMENTAL

Participants will receive one (1) cycle of atezolizumab, 1200mg intravenously (IV) over 30-60 minutes on day 1 of a 14 day cycle and etrumadenant will be taken at a dose of 150mg PO, once daily, until 48 hours prior to RP, for at least 12 days. Radical Prostatectomy (RP) will occur 21 days (+/- 7 days) following the final dose of atezolizumab. No further study therapy will be administered following RP.

Drug: Atezolizumab; Drug: Etrumadenant

Cohort C (atezolizumab, tocilizumab)

EXPERIMENTAL

Participants will receive one (1) cycle of neoadjuvant atezolizumab and one (1) cycle of tocilizumab, 6mg/kg will be administered IV on day 1 of a 14 day IV prior to RP; atezolizumab will be administered in an identical fashion as Cohort A. RP will occur 21 days (+/- 7 days) following the final dose of atezolizumab. No further study therapy will be administered following RP.

Drug: Atezolizumab; Drug: Tocilizumab

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Cohort A (atezolizumab monotherapy); Cohort B (atezolizumab, etrumadenant); Cohort C (atezolizumab, tocilizumab)

Tocilizumab DRUG

Given IV

Also known as: Actemra

Cohort C (atezolizumab, tocilizumab)

Etrumadenant DRUG

Given Orally

Also known as: AB928

Cohort B (atezolizumab, etrumadenant)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed adenocarcinoma of the prostate.
• a. Subjects with small cell or neuroendocrine PC are not eligible.
• Eligible for radical prostatectomy as determined by urologic oncology surgeon, and subject consents to proceeding with radical prostatectomy.
• a. Deemed by urologic oncology surgeon to be appropriate for a "window-of-opportunity"study.
• Only patients with high-risk disease are eligible for the safety lead-in for each cohort. Patients with intermediate-risk disease will be included after interim analyses is complete for the corresponding cohort and the PI has determined that it is safe to do so.
• Availability of a representative tumor specimen that is suitable for the planned study analyses, as determined by the Principal Investigator.
• A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report prior to study treatment. If only 10-14 slides are available, the patient may still be eligible for the study, after Principal Investigator approval has been obtained.
• If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening. Refer to Section 6.3 for additional information on tumor specimens collected at screening.

You may not qualify if:

• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Requirements for organ and marrow function:
• Hemoglobin \>= 9 g/dL
• \- Participants must not have been transfused within 2 weeks prior to screening to meet this criterion
• Absolute neutrophil count \>= 1,500/microliter (uL) without granulocyte colonystimulating factor support
• Absolute lymphocyte count \>= 500/uL
• Platelets \>= 100,000/uL without transfusion
• Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (known Gilbert disease: \< 3 x ULN)
• Alkaline phosphatase \< 2 x institutional ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) =\< 2 x institutional ULN
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =\< 2 x institutional ULN
• International normalized ratio (INR) or activated partial thromboplastin time (aPTT) \< 1.5 x institutional ULN for subjects not receiving therapeutic anticoagulation
• Creatinine clearance \>= 30 mL/min (calculated using the Cockcroft-Gault formula)
• Serum creatinine \<=1.6 mg/dL (141 μmol/L) in female patients and ≤1.9 mg/dL (168 μmol/L) in male patients . Patients with serum creatinine values exceeding limits may be eligible for the study if their estimated glomerular filtration rates (GFR) are \>30

Sponsors & Collaborators

• David Oh: lead
• Genentech, Inc.: collaborator
• Arcus Biosciences, Inc.: collaborator

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Alvin J. Siteman Cancer Center at Washington University

St Louis, Missouri, 63110, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

atezolizumab; tocilizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• David Oh, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

UCSF HDFCCC Cancer Immunotherapy Program (CIP)

CONTACT

877-827-3222; HDFCCC.CIP@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 10, 2019
• First Posted: January 29, 2019
• Study Start: October 30, 2019
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)