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

NCT ID: NCT03486197

Last Updated: 2024-11-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-17
• Study Completion Date: 2024-05-01

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.

Conditions

Urothelial Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Pembrolizumab

Intervention Type: BIOLOGICAL

Given IV

Radiation Therapy

Intervention Type: RADIATION

Undergo neutron radiation therapy

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Pembrolizumab

Given IV

Intervention Type: BIOLOGICAL

Radiation Therapy

Undergo neutron radiation therapy

Intervention Type: RADIATION

Other Intervention Names

Keytruda; Lambrolizumab; MK-3475; SCH 900475; Cancer Radiotherapy; Irradiate; Irradiated; irradiation; RADIATION; Radiotherapeutics; radiotherapy; RT; Therapy, Radiation

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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Jing Zeng

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jing Zeng

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2018-00412

Identifier Type: REGISTRY

Identifier Source: secondary_id

9940

Identifier Type: OTHER

Identifier Source: secondary_id

RG3118000

Identifier Type: OTHER

Identifier Source: secondary_id

9940

Identifier Type: -

Identifier Source: org_study_id