Clinical Trials /

Atezolizumab Given in Combination With a Personalized Vaccine in Patients With Urothelial Cancer

NCT03359239

Description:

The purpose of this study is to determine the good and bad effects of atezolizumab given in combination with a personalized cancer vaccine in patients with urothelial cancer either after surgery to remove organ where the tumor arose (for example, removal of the bladder) or for urothelial cancer that has spread to other organs.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Atezolizumab Given in Combination With a Personalized Vaccine in Patients With Urothelial Cancer
  • Official Title: Pilot Study of Atezolizumab Plus PGV001, a Multipeptide Personalized Neoantigen Vaccine, in Patients With Locally Advanced or Metad or Metastatic Urothelial Cancer

Clinical Trial IDs

  • ORG STUDY ID: GCO 16-1387
  • NCT ID: NCT03359239

Conditions

  • Urothelial/Bladder Cancer, Nos

Interventions

DrugSynonymsArms
AtezolizumabTECENTRIQPGV 001 with Atezolizumab
PGV001PGV 001 with Atezolizumab
Poly ICLCPGV 001 with Atezolizumab
Normal salinePGV 001 with Atezolizumab

Purpose

The purpose of this study is to determine the good and bad effects of atezolizumab given in combination with a personalized cancer vaccine in patients with urothelial cancer either after surgery to remove organ where the tumor arose (for example, removal of the bladder) or for urothelial cancer that has spread to other organs.

Detailed Description

      This is a single arm, proof-of-concept study. Fifteen subjects with urothelial cancer
      interested in participation will sign a "tissue acquisition and vaccine preparation consent"
      after which tumor tissue will be obtained from either a surgical resection specimen or
      biopsy. Subjects are scheduled to undergo cystectomy or nephroureterectomy for invasive
      urothelial cancer may consent prior to, or within 6 weeks after, surgery. The tumor specimen
      will be submitted for genomic sequencing followed by neoantigen identification utilizing a
      computational pipeline. Peptides corresponding to these neoantigens will be prepared for the
      personalized vaccine product. Subjects eligible for the treatment phase of the protocol
      (i.e., after surgery in adjuvant patients and chemotherapy in metastatic patients) will
      receive atezolizumab every 3 weeks plus up to ten doses of PGV001 vaccination plus Poly-ICLC.
      The primary objectives will be to determine the feasibility and safety of administration of a
      personalized neoantigen-based vaccine (PGV001) plus atezolizumab in subjects with locally
      advanced or metastatic urothelial cancer.
    

Trial Arms

NameTypeDescriptionInterventions
PGV 001 with AtezolizumabExperimentalAtezolizumab: programmed death-ligand 1 PGV001:personalized cancer vaccine PGV 001 - vaccine Poly ICLC- adjuvant The product is prepared within the Icahn School of Medicine at Mount Sinai (ISMMS) . The product consists of two independent preparations of patient specific long peptides mixed with poly-ICLC.
  • Atezolizumab
  • PGV001
  • Poly ICLC
  • Normal saline

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent and HIPAA authorization for release of personal health
             information.

          -  Age ≥ 18 years at the time of consent.

          -  ECOG Performance Status of ≤ 1 within fourteen days of registration for protocol
             therapy.

          -  Histological or cytological evidence of urothelial cancer of the bladder, urethra,
             ureter, or renal pelvis. Differentiation with variant histologies (e.g., squamous cell
             differentiated) will be permitted provided that the predominant histology is
             urothelial carcinoma.

          -  Clinical disease state specific criteria:

               -  Subjects with invasive urothelial cancer of the bladder or upper urinary tract
                  may consent either before or within 6 weeks after radical cystectomy or
                  nephroureterectomy.

               -  Subjects with metastatic and/or unresectable disease must have a metastatic site
                  amenable to biopsy. In situations where a metastatic biopsy does not yield
                  sufficient genetic material for sequencing, or a biopsy cannot be feasibly
                  performed, the use of archival tumor tissue may be considered on a case by case
                  basis. The archival tissue must be derived from a muscle-invasive urothelial
                  cancer specimen or metastatic urothelial cancer specimen.

          -  Required laboratory values must be obtained within thirty days of consent.

               -  ANC ≥ 1500 cells/µL

               -  WBC counts > 2500/µL

               -  Lymphocyte count ≥ 300/µL

               -  Platelet count ≥ 100,000/µL

               -  Hemoglobin ≥ 8.0 g/dL

               -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN) with the following exception:

                  o Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN
                  may be enrolled.

               -  AST and ALT ≤ 3.0 x ULN with the following exception:

                  o Patients with liver involvement: AST and/or ALT ≤ 5 x ULN

               -  Alkaline phosphatase ≤ 2.5 x ULN with the following exception:

                  o Patients with documented liver involvement or bone metastases: alkaline
                  phosphatase ≤ 5 x ULN

               -  Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 30 mL/min on the basis of
                  the Cockcroft-Gault glomerular filtration rate estimation:

               -  (140 - age) x (weight in kg) x (0.85 if female) / 72 x (serum creatinine in
                  mg/dL)

               -  INR and aPTT ≤ 1.5 x ULN o This applies only to patients who do not receive
                  therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such
                  as low-molecular-weight heparin or warfarin) should be on a stable dose.

        Exclusion Criteria:

          -  Known clinically significant liver disease, including active viral, alcoholic, or
             other hepatitis; cirrhosis; fatty liver; and inherited liver disease

          -  Symptomatic CNS metastases and/or metastases to brain stem, midbrain, pons, medulla,
             cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm) and/or
             history of intracranial hemorrhage or spinal cord hemorrhage

          -  Pregnancy, lactation, or breastfeeding

          -  Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

          -  History or risk of autoimmune disease, including but not limited to systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's
             syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune
             thyroid disease, vasculitis, or glomerulonephritis

          -  Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
             replacement hormone may be eligible.

          -  Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be
             eligible.

          -  Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with
             dermatologic manifestations only (e.g., patients with psoriatic arthritis would be
             excluded) are permitted provided that they meet the following conditions:

          -  History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
             pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
             tomography (CT) scan

             o History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

          -  History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C
             infection

          -  Active tuberculosis

          -  A known additional primary malignancy that is progressing or requires active
             treatment. Exceptions include cancers that have undergone potentially curative
             therapy.

          -  Medication-Related Exclusion Criteria:

               -  Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway
                  targeting agents

               -  No history of severe immune-related adverse effects from anti-CTLA 4 (NCI CTCAE
                  Grade 3 and 4)

               -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
                  chimeric or humanized antibodies or fusion proteins

               -  Patients with prior allogeneic bone marrow transplantation or prior solid organ
                  transplantation

        Please contact site for other inclusion/exclusion criteria.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of neoantigens
Time Frame:up to 24 months
Safety Issue:
Description:Feasibility parameter: Number of neoantigens identified per subject

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:up to 24 hours
Safety Issue:
Description:Objective Response Rate by RECIST 1.1 . RECIST: complete response, partial response, stable disease, and progressive disease.
Measure:Duration of response
Time Frame:up to 24 months
Safety Issue:
Description:The duration of response by RECIST 1.1 and immune-related RECIST criteria in patients with metastatic disease
Measure:Time to Progression In Adjuvant patients
Time Frame:up to 24 months
Safety Issue:
Description:Time-to-progression in adjuvant patients using RECIST: complete response, partial response, stable disease, and progressive disease
Measure:Overall Survival
Time Frame:up to 24 months
Safety Issue:
Description:Number of participants living

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Matthew Galsky

Trial Keywords

  • PGV001
  • atezolizumab
  • urothelial cancer
  • personalized neoantigen vaccine

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