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

• ClinicalTrials.gov Identifier: NCT03486197
• Recruitment Status: Active, not recruiting
• First Posted: April 3, 2018
• Last Update Posted: February 17, 2023
• Sponsor: University of Washington
• Information provided by (Responsible Party): University of Washington

Tracking Information

• First Submitted Date: March 27, 2018
• First Posted Date: April 3, 2018
• Last Update Posted Date: February 17, 2023
• Actual Study Start Date: January 17, 2019
• Estimated Primary Completion Date: November 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 27, 2018)

Overall response rate per immune-modified response evaluation criteria in solid tumors [ Time Frame: Up to 3 years ]

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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 27, 2018)

• Overall survival [ Time Frame: Up to 3 years ]
  This will be estimated with the Kaplan and Meier method with 95% CI obtained using Greenwood estimates of variance.
• Progression-free survival [ Time Frame: Up to 3 years ]
  This will be estimated with the Kaplan and Meier method with 95% CI obtained using Greenwood estimates of variance.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Neutron Radiation Therapy and Pembrolizumab in Treating Participants With Advanced Urothelial Carcinoma
• Official Title: Phase II Trial of Neutron Radiotherapy With Concurrent Checkpoint Inhibitor Immunotherapy (Pembrolizumab) in Patients With Advanced Urothelial Carcinoma
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Urothelial Carcinoma

Intervention

• Other: Laboratory Biomarker Analysis
  Correlative studies
• Biological: Pembrolizumab
  Given IV
  Other Names:

  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475
• Radiation: Radiation Therapy
  Undergo neutron radiation therapy
  Other Names:

  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • RADIATION
  • Radiotherapeutics
  • radiotherapy
  • RT
  • Therapy, Radiation

Study Arms

Experimental: 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.

Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 15, 2023): 13
• Original Estimated Enrollment (submitted: March 27, 2018): 20
• Estimated Study Completion Date: May 1, 2024
• Estimated Primary Completion Date: November 1, 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03486197
• Other Study ID Numbers: 9940; NCI-2018-00412 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 9940 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ); RG3118000 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of Washington
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Washington
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jing Zeng; Fred Hutch/University of Washington Cancer Consortium

• PRS Account: University of Washington
• Verification Date: February 2023