Urothelial Carcinoma
Conditions
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALPembrolizumab
Given IV
RADIATIONRadiation Therapy
Undergo neutron radiation therapy
Sponsors
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate Per Immune-modified Response Evaluation Criteria in Solid Tumors | Up to 1 year | Overall response rate will be calculated as the percentage of patients achieving a partial response or complete response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | At 1 year | Final statistical analyses of OS will consist of Kaplan-Meier estimation. |
| Progression-free Survival | At 1 year | Final statistical analyses of PFS will consist of Kaplan-Meier estimation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Laboratory Biomarker Analysis: Correlative studies
Pembrolizumab: Given IV
Radiation Therapy: Undergo neutron radiation therapy | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Treatment (Pembrolizumab, Neutron Radiation Therapy) |
|---|---|
| Age, Continuous | 71 years STANDARD_DEVIATION 9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 12 |
| other Total, other adverse events | 9 / 12 |
| serious Total, serious adverse events | 2 / 12 |
Outcome results
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.
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Pembrolizumab, Neutron Radiation Therapy) | Overall Response Rate Per Immune-modified Response Evaluation Criteria in Solid Tumors | 6 Participants |
Secondary
Overall Survival
Final statistical analyses of OS will consist of Kaplan-Meier estimation.
Time frame: At 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Pembrolizumab, Neutron Radiation Therapy) | Overall Survival | 62 percentage of participants |
Secondary
Progression-free Survival
Final statistical analyses of PFS will consist of Kaplan-Meier estimation.
Time frame: At 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Pembrolizumab, Neutron Radiation Therapy) | Progression-free Survival | 55 percentage of participants |