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

NCT03486197 | Terminated Phase 2 Results FDA Drug FDA Device

• 3 other identifiers: 9940NCI-2018-00412RG3118000
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 1 year

Secondary Outcomes (2)

• Overall Survival

  At 1 year

• Progression-free Survival

  At 1 year

Study Arms (1)

Treatment (Pembrolizumab, neutron radiation therapy)

EXPERIMENTAL

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.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Radiation: Radiation Therapy

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (Pembrolizumab, neutron radiation therapy)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (Pembrolizumab, neutron radiation therapy)

Radiation Therapy RADIATION

Undergo neutron radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, RADIATION, Radiotherapeutics, radiotherapy, RT, Therapy, Radiation

Treatment (Pembrolizumab, neutron radiation therapy)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

pembrolizumab; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Dr. Jing Zeng
• Organization: University of Washington/Fred Hutch Cancer Center Proton Therapy

jzeng13@uw.edu

2065984110

Study Officials

• Jing Zeng

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 27, 2018
• First Posted: April 3, 2018
• Study Start: January 17, 2019
• Primary Completion: November 1, 2023
• Study Completion: May 1, 2024
• Last Updated: November 20, 2024
• Results First Posted: November 20, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)