Clinical Trials /

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

NCT03486197

Description:

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.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 9940
  • SECONDARY ID: NCI-2018-00412
  • SECONDARY ID: 9940
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: RG3118000
  • NCT ID: NCT03486197

Conditions

  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (Pembrolizumab, neutron radiation therapy)

Purpose

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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (Pembrolizumab, neutron radiation therapy)ExperimentalParticipants 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.
  • Pembrolizumab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate per immune-modified response evaluation criteria in solid tumors
Time Frame:Up to 3 years
Safety Issue:
Description: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

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

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