Clinical Trials /

Pembrolizumab in Treating Patients With Bladder Cancer Undergoing Radical Cystectomy

NCT03319745

Description:

This phase II trial studies the side effects of pembrolizumab and to see how well it works in treating patients with bladder cancer who are undergoing surgery to remove the bladder. 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.

Related Conditions:
  • Bladder Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Treating Patients With Bladder Cancer Undergoing Radical Cystectomy
  • Official Title: A Window of Opportunity Phase II Study of Pembrolizumab in Patients With Bladder Cancer Undergoing Radical Cystectomy

Clinical Trial IDs

  • ORG STUDY ID: 2017-0057
  • SECONDARY ID: NCI-2018-01032
  • SECONDARY ID: 2017-0057
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03319745

Conditions

  • Stage I Bladder Cancer AJCC v8
  • Stage II Bladder Cancer AJCC v8
  • Stage III Bladder Cancer AJCC v8
  • Stage IIIA Bladder Cancer AJCC v8
  • Stage IIIB Bladder Cancer AJCC v8

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab)

Purpose

This phase II trial studies the side effects of pembrolizumab and to see how well it works in treating patients with bladder cancer who are undergoing surgery to remove the bladder. 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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To characterize the safety profile of pembrolizumab in patients with urothelial carcinoma
      undergoing radical cystectomy.

      SECONDARY OBJECTIVES:

      I. To explore a signal of anti-cancer immunological activity by evaluating surgical specimens
      for evidence of post-treatment lymphocytic infiltration and residual tumor compared to
      pre-treatment biopsy samples.

      II. To explore a signal of biomarker activity by evaluating surgical specimens and blood
      samples for established and not-so-established markers of response to pembrolizumab.

      III. To report the tumor yield and sufficiency of tumor for immunological and biomarker
      activity

      SECONDARY OBJECTIVES:

      I. To explore a signal of anti-cancer immunological activity by evaluating surgical specimens
      for evidence of post-treatment lymphocytic infiltration and residual tumor compared to
      pre-treatment biopsy samples.

      II. To explore a signal of biomarker activity by evaluating surgical specimens and blood
      samples for established and not-so-established markers of response to pembrolizumab.

      III. To report the tumor yield and sufficiency of tumor for immunological and biomarker
      activity.

      IV. To examine the interaction of the human microbiome and pathologic response to
      pembrolizumab.

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat
      every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable
      toxicity. About 4 weeks after treatment, patients then undergo radical cystectomy per
      standard of care.

      After completion of study treatment, patients are followed up to 30 and 90 days.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. About 4 weeks after treatment, patients then undergo radical cystectomy per standard of care.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent.

          -  Have absence of metastatic disease as determined by conventional imaging studies and
             be considered a good surgical candidate by the treating physician.

          -  Be willing to participate in the collection of blood and tissue for banking and future
             correlative studies.

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale.

          -  Absolute neutrophil count (ANC) >= 1,500 /mcL.

          -  Platelets >= 100,000/mcL.

          -  Hemoglobin (Hgb) >= 9 g/dL or >= 5.6 mmol/L without (w/o) transfusion within 7 days of
             assessment.

          -  Creatinine OR calculated creatinine clearance =< 1.5 x upper limit of normal (ULN) OR
             >= 30 mL/min for subject with creatinine levels > 1.5 x institutional ULN. Creatinine
             clearance should be calculated per institutional standard.

          -  Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total
             bilirubin levels > 1.5 x ULN

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
             ULN OR =< 5 x ULN for subjects with liver metastases.

          -  Albumin > 2.5 mg/dL.

          -  Coagulation international normalized ratio (INR) or prothrombin time (PT) activated
             partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving
             anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
             of anticoagulants.

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

          -  Female subjects of childbearing potential must be willing to use an adequate method of
             contraception for the course of the study through 120 days after the last dose of
             study medication. Note: Abstinence is acceptable if this is the usual lifestyle and
             preferred contraception for the subject.

          -  Male subjects of childbearing potential must agree to use an adequate method of
             contraception, starting with the first dose of study therapy through 120 days after
             the last dose of study therapy. Note: Abstinence is acceptable if this is the usual
             lifestyle and preferred contraception for the subject.

        Exclusion Criteria:

          -  Is currently participating and receiving pembrolizumab or has participated in a study
             of an investigational agent and received pembrolizumab or used an investigational
             device within 4 weeks of the first dose of study treatment.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of study
             treatment.

          -  Has a known history of active TB (Bacillus tuberculosis).

          -  Has a known history of hypersensitivity to pembrolizumab or any of its excipients.

          -  Has had prior systemic anti-cancer therapy for the treatment of bladder cancer. Prior
             intravesical therapies, whether Bacillus Calmette-Guerin (BCG) (including but not
             limited to: persistent high-grade disease or recurrence within 6 months of receiving
             at least two courses of intravesical BCG [at least five of six induction doses and at
             least two of three maintenance doses]; or T1 high-grade disease at the first
             evaluation following induction BCG alone [at least five of six induction doses]),
             chemotherapy or otherwise, will remain eligible.

          -  Has any other malignancy diagnosed within 2 years of screening with the exception of
             basal or squamous cell skin cancer, or non-invasive cancer of the cervix, or any other
             cancer deemed by the treating physician to be of low-risk for progression or patient
             morbidity during the study period.

          -  Has known metastatic disease as determined by conventional staging studies.

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          -  Has known history of, or any evidence of active, non-infectious pneumonitis.

          -  Has a clinically significant active infection requiring systemic therapy.

          -  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 physician.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose\ of trial 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 surface antigen [HBsAg] reactive) or
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
             detected).

          -  Has received a live vaccine within 30 days of initiation of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live
             attenuated vaccines, and are not allowed.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0
Time Frame:Up to 30 days post-surgery
Safety Issue:
Description:Toxicity of concern (TOX) will be monitored using the methods of Thall et al. TOX events will be reported with a 95% credible interval assuming a non-informative prior of beta. Specific events will also be summarized. All adverse events and surgical complications will be reported overall by grade, attribution, and treatment period.

Secondary Outcome Measures

Measure:Biomarker activity of Pembrolizumab in Patients with Bladder Cancer Undergoing Radical Cystectomy
Time Frame:Baseline up to 90 days after surgery
Safety Issue:
Description:Tissue evaluated for signals of biomarker activity by evaluating surgical specimens for established and not-so-established markers of response to pembrolizumab (e.g. TILS, PD-1 and PD-L1 levels) compared to pre-treatment biopsy samples.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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