Clinical Trials /

Study of Personalized Tumor Vaccines (PCVs) and a PD-L1 Blocker in Patients With Pancreatic Cancer That Can be Treated With Surgery

NCT04161755

Description:

The purpose of this study is to evaluate the safety or treating pancreatic cancer with surgery to remove cancerour tissue, followed by atezolizumab, followed by a personalized cancer vaccine (PCV), and then with chemotherapy.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Personalized Tumor Vaccines (PCVs) and a PD-L1 Blocker in Patients With Pancreatic Cancer That Can be Treated With Surgery
  • Official Title: Phase 1 Clinical Trial of Personalized Neoantigen Tumor Vaccines and Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Surgically Resected Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19-039
  • NCT ID: NCT04161755

Conditions

  • Pancreatic Cancer

Interventions

DrugSynonymsArms
AtezolizumabPancreatic Cancer
RO7198457Pancreatic Cancer
mFOLFIRINOXPancreatic Cancer

Purpose

The purpose of this study is to evaluate the safety or treating pancreatic cancer with surgery to remove cancerour tissue, followed by atezolizumab, followed by a personalized cancer vaccine (PCV), and then with chemotherapy.

Trial Arms

NameTypeDescriptionInterventions
Pancreatic CancerExperimentalRadiologically resectable primary pancreatic tumors
  • Atezolizumab
  • RO7198457
  • mFOLFIRINOX

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must be >/= 18 years of age at time of informed consent

          -  Able to comply with the study protocol, in the investigator's judgment

          -  Subjective with radiographically resectable primary pancreatic tumors with
             radiographic features consistent with adenocarcinoma will be evaluated for surgical
             resection

          -  Tumors must be radiographically resectable, defined as:

               -  A clear fat plane around the celiac and superior mesenteric arteries

               -  patent superior mesenteric and portal veins without primary tumor involvement

               -  No encasement of the superior mesenteric vein or portal veins

               -  No encasement of the superior mesenteric or hepatic arteries

               -  No metastatic disease

               -  No extra-regional nodal disease

          -  Subjects with histologically confirmed resected ductal pancreatic adenocarcinoma with
             macroscopic complete resection (R0 and R1) will be selected for neoantigen vaccine
             creation. Subjects with neuroendocrine (and mixed type) tumors are excluded

          -  Pancreatic cancer surgical staging: T 1-3, N0-2, M0

             ° Per AJCC 8th edition staging

          -  Performance status of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) Scale of
             Performance Status (Section 20.0 APPENDICES, Appendix1)

          -  Ca19-9<100U/mL assessed within 14 days prior to surgery

          -  Subjects must not have had prior chemotherapy, radiation therapy, or immunotherapy for
             PDAC

          -  Subjects must be able to read, understand, and sign informed consent

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             within 14 days prior to study initiation

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive measures that result in a failure rate
             of less than (<) 1% per year during the treatment period and for at least 5 months
             after the last dose of atezolizumab and for at least 90 days after the last dose of
             RO7198457. A woman is considered to be of childbearing potential if she is
             postmenarcheal, has not reached a postmenopausal state (>/= 12 continuous months of
             amenorrhea with no identified cause other than menopause), and has not undergone
             surgical sterilization (removal of ovaries and/or uterus)

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             a condom during the entire study period and up to 90 days after last administration of
             RO7198457. Male participants should not donate sperm for 90 days after the last dose
             of RO7198457

          -  Examples of contraceptive methods with a failure rate of <1% per year include
             bilateral tubal ligation, male sterilization and established proper use of hormonal
             contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and
             copper intrauterine devices

          -  Hormonal contraceptive methods must be supplemented by a barrier method plus
             spermicide

          -  The reliability of sexual abstinence should be evaluated in relation to the duration
             of the clinical trial and the preferred and usual lifestyle of the patient. Periodic
             abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
             withdrawal are not acceptable methods of contraception

        Tumor Sample Inclusion Criteria

          -  Patients with confirmed availability of representative resection tumor specimens in
             formalin-fixed, paraffin-embedded (FFPE) blocks, or sectioned tissue (as described in
             the laboratory manual) with an associated pathology report

          -  Multiple samples may be collected for a given patient, on the basis of availability;
             however, the requirement for a block or sectioned tissue should be satisfied by a
             single resection specimen.

          -  A patient with insufficient or unavailable resection tumor tissue will not be eligible
             due to the need for evaluable tumor tissue to manufacture RO198457

          -  Enrollment will be limited to patients with at least five identified tumor neoantigens
             and sufficient tumor material (both quality and quantity) to manufacture vaccine

        Exclusion Criteria:

        A subject will not be eligible for inclusion in this study if any of the following criteria
        apply:

          -  Prior neoadjuvant treatment or radiation therapy for PDAC

          -  Prior therapy with uPD-1 antibody or any other immune therapy

          -  Borderline resectable, locally unresectable or metastatic PDAC

          -  Pancreas tumor histology other than PDAC

          -  Pregnancy, breastfeeding, or intending to become pregnant during the study or within
             90 days after the last dose of study treatment

          -  Life expectancy less than 12 weeks

          -  Inability to comply with study and/or follow-up procedures

          -  Any other malignancy within 5 years of study enrollment, with the exception of
             adequately treated in-situ carcinoma of the cervix uteri, or non-melanomatous skin
             cancer

          -  Patients with unresolved Clavien-Dindo >/= Grade 3 (Section 20.0 APPENDICES ,Appendix
             2) postoperative complications

          -  Actie, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic
             therapy, defined as ongoing signs/symptoms related to the infection without
             improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment

          -  Active tuberculosis

          -  Known infection with hepatitis B or C, or history of human immunodeficiency virus
             (HIV) infection or subjects receiving immunosuppressive or myelosuppressive
             medications that would, in the opinion of the investigator, increase the risk of
             serious neutropenic complications

          -  Known hypersensitivity or allergy to the active substance or to any of the excipients
             of RO7198457, atezolizumab, oxaliplatin, leucovorin, irinotecan, or fluorouracil

          -  Serious medical risk factors involving any of the major organ systems, or serious
             psychiatric disorders, which could compromise the subject's safety or the study data
             integrity. These include, but are not limited to:

               -  History of connective tissue disorders (e.g., lupus, scleroderma, arteritis
                  nodosa)

               -  History of interstitial lung disease, slowly progressive dyspnea and unproductive
                  cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary
                  hypersensitivity pneumonitis, or multiple allergies

               -  History of the following within 6 months prior to RO7198457 administration: a
                  myocardial infarction, severe/unstable angina pectoris, coronary/peripheral
                  artery bypass graft, New York Heart Association (NYHA) Class III-IV heart
                  failure, uncontrolled hypertension, clinically significant cardiac dysthythmia,
                  or electrocardiogram (ECG) abnormality (exceptions: atrial fibrillation,
                  paroxysmal supraventricular tachycardia), cerebrovascular accident, transient
                  ischemic attack,, or seizure disorder

          -  History or autoimmune disease, including but not limited to systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
             associated with antiphospholipid syndrome Wegener's granulomatosis, Sjogren's
             syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or
             glomerulonephritis with the following caveats:

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

               -  Patient with controlled type 1 diabetes mellitus on a stable insulin regimen may
                  be eligible

               -  Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
                  dermatologic manifestations only (e.g., no psoriatic arthritis) may be eligible
                  provided that they meet the following conditions:

          -  Rash must cover less than 10% of the body surface area (BSA)

          -  Disease is well controlled at baseline and only requires low potency topical steroids

          -  No acute exacerbations of underlying condition within the last 12 months (e.g., not
             requiring psorlen and ultraviolet A (PUVA) radiation, methotrexate retinoids, biologic
             agents, oral calcineurin inhibitors, high potency, or oral steroids)

          -  Treatment with systemic immunosuppressive medication (including but not limited to
             prednisone >10mg/day, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
             TNF-x antagonists) within 2 weeks prior to RO7198457 administration. Patients who have
             received acute, low-dose, systemic immunosuppressant medication (e.g., a one-time dose
             of dexamethasone for nausea) may be enrolled in the study after discussion with and
             approval by the PI and Co-PI. The use of inhaled corticosteroids (e.g., fluticasone
             for chronic obstructive pulmonary disease) is allowed. The use of oral
             mineralocorticoids (e.g., flurocortisone for patients with orthostatic hypotension) is
             allowed. Physiologic doses of corticosteroids for adrenal insufficiency are allowed.

          -  Subjects with allergies to IV contrast agents requiring pretreatment with
             corticosteroids will be excluded. Corticosteroids are immunosuppressive and may
             interfere with RO7198457 tolerability and efficacy. Given that there are serial
             contrast agent-dependent follow-up imaging studies built into the study which will
             overlap with vaccination, subjects who require pretreatment with corticosteroids prior
             to IV contrast administration will be excluded

          -  History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
             organizing pneumonia (i.e., bronchioloitis obliterans, cryptogenic organizing
             pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan.
             History of radiation pneumonitis in the radiation field (fibrosis) is permitted

          -  Known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T-negative
             severe combined immunodeficiency [SCID]) or combined T- and B-cell immunodeficiencies
             (e.g., T- and B-negative SCID, Wiskott-Aldrich syndrome, ataxia telangiectasia, common
             variable immunodeficiency)

          -  Prior allogeneic bone marrow transplantation or prior solid organ transplantation

          -  Any other disease, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that would
             contraindicate the use of an investigational drug

          -  Known clinically significant liver disease, including active viral, alcoholic, or
             other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse

          -  Previous splenectomy

          -  Administration of a live, attenuated vaccine within 4 weeks before RO7198457
             administration or anticipation that such a live attenuated vaccine will be required
             during the study. Influenza vaccination should be given during influenza season only.
             Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4
             weeks prior to RO7198457 administration or at any time during the study, and for 90
             days following the last study treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Drug related toxicity
Time Frame:2 years
Safety Issue:
Description:The primary objective of this trial is to evaluate the safety of a personalized tumor vaccine combined with atezolizumab and mFOLFIRINOX

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • personalized tumor vaccines
  • PCVs
  • PD-L1 Blocker
  • Memorial Sloan Kettering Cancer Center
  • 19-039

Last Updated

December 19, 2019