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

Pilot Study of Atezolizumab Plus PGV001, a Multipeptide Personalized Neoantigen Vaccine, in Patients With Locally Advanced or Metad or Metastatic Urothelial Cancer

INTRODUCTION

  • Org Study ID: GCO 16-1387
  • Secondary ID: N/A
  • NTC ID: NCT03359239
  • Sponsor: Matthew Galsky

BRIEF SUMMARY

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.

  • Overall Status
    Recruiting
  • Start Date
    May 8, 2019
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Number of neoantigens

Primary Outcome 1 - Timeframe: up to 24 months

Primary Outcome 2 - Measure: Number of peptides synthesized

Primary Outcome 2 - Timeframe: up to 24 months

Primary Outcome 3 - Measure: Vaccine Production time

Primary Outcome 3 - Timeframe: up to 24 months

Primary Outcome 4 - Measure: Proportion of consent to tissue acquisition phase

Primary Outcome 4 - Timeframe: up to 24 months

Primary Outcome 5 - Measure: Proportion of subjects eligible for the treatment phase

Primary Outcome 5 - Timeframe: up to 24 months

Primary Outcome 6 - Measure: Number of toxicities

Primary Outcome 6 - Timeframe: up to 24 months

CONDITION

  • Urothelial/Bladder Cancer
  • Nos

ELIGIBILITY

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) or pure variant histologies 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Matthew Galsky, MD

Role: Principal Investigator

Affiliation: Icahn School of Medicine at Mount Sinai

Overall Contact

Name: Matthew Galsky, MD

Phone: (212) 824-7860 (x57860)

Email: Lynn.Bui@mssm.edu

LOCATION

Facility Status Contact
Facility: Icahn School of Medicine at Mount Sinai
New York, New York 10029
United States
Status: Recruiting Contact: N/A