Phase II Trial of Neutron Radiotherapy With Concurrent Checkpoint Inhibitor Immunotherapy (Pembrolizumab) in Patients With Advanced Urothelial Carcinoma

University of Washington1 site in 1 country12 target enrollmentJanuary 17, 2019

Overview

Brief Summary

This phase II trial studies how well neutron radiation therapy and pembrolizumab work in treating participants with urothelial carcinoma that has spread to other places in the body. Neutron radiation therapy uses high energy neutrons to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving radiation therapy and pembrolizumab may work better than radiation alone in treating participants with urothelial carcinoma that has spread to other places in the body.

Detailed Description

OUTLINE: Participants receive pembrolizumab intravenously (IV) on days 1 and 22. On day 23, participants may undergo an optional tumor biopsy and receive 3-5 treatments of neutron radiation therapy over 2 weeks on days 23-42. Participants receive pembrolizumab IV on day 43 and continue per standard of care in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up every 3 months.

Registry

clinicaltrials.gov

Start Date

January 17, 2019

End Date

May 1, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Washington

Responsible Party

Principal Investigator

Jing Zeng

Professor

University of Washington

Eligibility Criteria

Inclusion Criteria

•Pathologically proven (either histologic or cytologic) diagnosis of urothelial carcinoma
•At least two sites of disease that are measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
•Eligible for checkpoint inhibitor immunotherapy (pembrolizumab) per standard of care
•No history of autoimmune disease requiring systemic therapy (e.g. steroids or biologic agents)
•Absolute neutrophil count (ANC) ≥ 1500 /mcL
•Platelets ≥ 100,000/mcL
•Hemoglobin \> 9 g/dL
•Creatinine ≤ 1.5 x upper limit of normal (ULN) OR ≥ 60 mL/min
•Total bilirubin ≤ 1.5 ULN OR direct bilirubin ≤ ULN if total bilirubin \> 1.5 x ULN
•Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN OR \< 5 x ULN if patient has liver metastasis

Exclusion Criteria

•Has a known history of active TB (Bacillus tuberculosis)
•Hypersensitivity to pembrolizumab or any of its excipients
•Has a known additional malignancy that is progressing or requires active treatment
•Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
•Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
•Has known active hepatitis B (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
•Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
•Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
•Has known history of, or any evidence of active, non-infectious pneumonitis
•Has an active infection requiring systemic therapy

Arms & Interventions

Treatment (Pembrolizumab, neutron radiation therapy)

Participants receive pembrolizumab IV on days 1 and 22. On day 23, participants may undergo an optional tumor biopsy and receive 3-5 treatments of neutron radiation therapy over 2 weeks on days 23-42. Participants receive pembrolizumab IV on day 43 and continue per standard of care in the absence of disease progression or unacceptable toxicity.

Intervention: Laboratory Biomarker Analysis

Treatment (Pembrolizumab, neutron radiation therapy)

Participants receive pembrolizumab IV on days 1 and 22. On day 23, participants may undergo an optional tumor biopsy and receive 3-5 treatments of neutron radiation therapy over 2 weeks on days 23-42. Participants receive pembrolizumab IV on day 43 and continue per standard of care in the absence of disease progression or unacceptable toxicity.

Intervention: Pembrolizumab

Treatment (Pembrolizumab, neutron radiation therapy)

Participants receive pembrolizumab IV on days 1 and 22. On day 23, participants may undergo an optional tumor biopsy and receive 3-5 treatments of neutron radiation therapy over 2 weeks on days 23-42. Participants receive pembrolizumab IV on day 43 and continue per standard of care in the absence of disease progression or unacceptable toxicity.

Intervention: Radiation Therapy