Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03486197
Recruitment Status : Recruiting
First Posted : April 3, 2018
Last Update Posted : June 11, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

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.

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Radiation: Radiation Therapy Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the overall response rate to neutron radiation (with high relative biological effectiveness relative to standard photon radiation) to a metastatic focus in combination with standard of care checkpoint inhibitor immunotherapy (pembrolizumab), in patients with advanced urothelial carcinoma.

SECONDARY OBJECTIVES:

I. Progression free survival.

II. Overall survival.

III. Safety and tolerability as evaluated by the incidence, severity, duration, causality, seriousness, and type(s) of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Neutron Radiotherapy With Concurrent Checkpoint Inhibitor Immunotherapy (Pembrolizumab) in Patients With Advanced Urothelial Carcinoma
Actual Study Start Date : January 17, 2019
Estimated Primary Completion Date : November 1, 2022
Estimated Study Completion Date : November 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03486197


Locations
Layout table for location information
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Jing Zeng    206-598-8822    lathap@uw.edu   
Principal Investigator: Jing Zeng         
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Jing Zeng Fred Hutch/University of Washington Cancer Consortium
Layout table for additonal information
Responsible Party: University of Washington
ClinicalTrials.gov Identifier: 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 )
P30CA015704 ( U.S. NIH Grant/Contract )
RG3118000 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
First Posted: April 3, 2018    Key Record Dates
Last Update Posted: June 11, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents