Neutron Radiation Therapy and Pembrolizumab in Treating Participants With Advanced Urothelial Carcinoma

Urothelial Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03486197
• Other study ID #: 9940
• Secondary ID: NCI-2018-0041299
• Status: Terminated
• Phase: Phase 2
• Start date: January 17, 2019
• Est. completion date: May 1, 2024

Study information

• Verified date: May 2024
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: May 1, 2024
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• Albumin >= 2.5 g/dL

• International normalized ratio (INR) or PT = 1.5 x ULN unless on anticoagulation therapy, in which case prothrombin time (PT) or partial thromboplastin time (PTT) should be in the therapeutic range

• PTT = 1.5 x ULN unless on anticoagulation therapy, in which case PT or PTT should be in the therapeutic range

• Eligible for neutron radiation treatment to 1-3 sites of metastatic disease (lesions do not have to be symptomatic)

• No steroids for at least 2 weeks prior to enrollment, and patient must not be expected to require steroids during the study period

• Zubrod performance status 0-2

• Patient must sign study specific informed consent prior to study entry

• Patients who are sexually active must use medically acceptable forms of contraception

• Life expectancy must be > 3 months

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

• Has received a live vaccine within 30 days of planned start of study therapy

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided there is no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Biological:
• Pembrolizumab
Given IV

Radiation:
• Radiation Therapy
Undergo neutron radiation therapy

Locations

Country	Name	City	State
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate per immune-modified response evaluation criteria in solid tumors	Overall response rate will be calculated as the percentage of patients achieving a partial response or complete response, and will be presented along with the 95% confidence interval (CI).	Up to 3 years
Secondary	Overall survival	This will be estimated with the Kaplan and Meier method with 95% CI obtained using Greenwood estimates of variance.	Up to 3 years
Secondary	Progression-free survival	This will be estimated with the Kaplan and Meier method with 95% CI obtained using Greenwood estimates of variance.	Up to 3 years