Clinical Trials /

Pilot Study With CY, Pembrolizumab, GVAX, and IMC-CS4 (LY3022855) in Patients With Borderline Resectable Adenocarcinoma of the Pancreas

NCT03153410

Description:

This study will be looking at whether combining cyclophosphamide, pembrolizumab (an antibody that blocks negative signals to T cells), GVAX (pancreatic cancer vaccine), and IMC-CS4 (LY3022855) (an antibody that blocks a molecule called CSF1-R which prevents the bodies ability to fight cancer) is effective (anti-tumor activity) and safe in patients with borderline resectable pancreatic cancer.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot Study With CY, Pembrolizumab, GVAX, and IMC-CS4 (LY3022855) in Patients With Borderline Resectable Adenocarcinoma of the Pancreas
  • Official Title: A Pilot Study of a GVAX Pancreas Vaccine (With Cyclophosphamide) in Combination With a PD-1 Blockade Antibody (Pembrolizumab) and a Macrophage Targeting Agent (CSF1R Inhibitor) for the Treatment of Patients With Borderline Resectable Adenocarcinoma of the Pancreas

Clinical Trial IDs

  • ORG STUDY ID: J1766
  • SECONDARY ID: IRB00130267
  • NCT ID: NCT03153410

Conditions

  • Pancreatic Cancer

Interventions

DrugSynonymsArms
CyclophosphamideCYCyclophosphamide, GVAX, Pembrolizumab and IMC-CS4
GVAXPanc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-NeoCyclophosphamide, GVAX, Pembrolizumab and IMC-CS4
PembrolizumabMK-3475, KEYTRUDA®Cyclophosphamide, GVAX, Pembrolizumab and IMC-CS4
IMC-CS4LY3022855Cyclophosphamide, GVAX, Pembrolizumab and IMC-CS4

Purpose

This study will be looking at whether combining cyclophosphamide, pembrolizumab (an antibody that blocks negative signals to T cells), GVAX (pancreatic cancer vaccine), and IMC-CS4 (LY3022855) (an antibody that blocks a molecule called CSF1-R which prevents the bodies ability to fight cancer) is effective (anti-tumor activity) and safe in patients with borderline resectable pancreatic cancer.

Trial Arms

NameTypeDescriptionInterventions
Cyclophosphamide, GVAX, Pembrolizumab and IMC-CS4Experimental
  • Cyclophosphamide
  • GVAX
  • Pembrolizumab
  • IMC-CS4

Eligibility Criteria

        Inclusion Criteria:

          -  Have histologically or cytologically proven adenocarcinoma of the pancreas.

          -  Patient's acceptance to have a core biopsy.

          -  Presence of at least one measurable lesion.

          -  Must not have metastatic disease.

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >20
             mm with conventional techniques or as >10 mm with spiral CT scan. See Section 10.1.2
             for the evaluation of measurable disease.

          -  Must have received last dose of stereotactic body radiotherapy no longer than 28 days
             prior to enrollment.

          -  Must have received last dose of chemotherapy at least 14 days or longer prior to entry
             into the study.

          -  Age >18 years.

          -  ECOG performance status 0-1.

          -  Patient's blood, kidney and liver function must within normal limits

          -  Must use an acceptable form of birth control while on study.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Currently is participating or has participated in a study using any investigational
             therapy within the past 28 days or is currently using an investigational device.

          -  Major surgery 28 days prior to study entry excluding minor procedures (dental work,
             skin biopsy, etc.), celiac plexus block, and biliary stent placement.

          -  Used any systemic steroids, immunosuppressant medications and anti-neoplastic
             treatment in the past 14 days.

          -  Prior treatment with immunotherapy agents (including, but not limited to: IL-2,
             interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or
             anti-CTLA-4 antibodies).

          -  Used any growth factors including, but not limited to, granulocyte-colony stimulating
             factor (G-CSF), GM-CSF, erythropoietin, within 14 days of study drug administration.
             Use of such agents while on study is also prohibited.

          -  Received any prophylactic vaccine within 14 days of first dose of study drug or
             received a live vaccine within 30 days of study treatment.

          -  Currently have or have history of certain study-specified heart, liver, kidney, lung,
             neurological, psychological, immune or other medical conditions.

          -  History of any autoimmune disease: inflammatory bowel disease, (including ulcerative
             colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis
             (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis (e.g.,
             Wegener's Granulomatosis), CNS or motor neuropathy considered to be of autoimmune
             origin (e.g., Guillian-Barre Syndrome, Myasthenia Gravis, Multiple Sclerosis).
             Patients with thyroid disease will be allowed.

          -  Has history of (non-infectious) pneumonitis that required steroids, history or
             evidence of interstitial lung disease or active, non-infectious pneumonitis.

          -  Has a pulse oximetry < 92% on room air.

          -  Evidence of ascites on imaging.

          -  Requires the use of home oxygen.

          -  Have known history of infection with HIV, hepatitis B, or hepatitis C.

          -  Have been diagnosed with another cancer in the past 5 years (except for superficial
             bladder cancer, non-melanoma skin cancers, or a low grade prostate cancer not
             requiring therapy)

          -  History of severe hypersensitivity reaction to any monoclonal antibody.

          -  Known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide,
             fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX
             pancreas vaccine.

          -  Pregnant or breastfeeding women.

          -  Positive pregnancy test during the study.

          -  Women sexually active with a fertile man and of childbearing potential unwilling or
             unable to use an acceptable method to avoid pregnancy for the entire study and for up
             to 120 days after the last dose of study drug.

          -  Unwilling or unable to follow the study schedule for any reason.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:CD8 T cell density in the primary tumor after neoadjuvant administration of combination immunotherapy by immunohistochemistry (IHC)
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:2 years
Safety Issue:
Description:
Measure:Disease free survival (DFS)
Time Frame:2 years
Safety Issue:
Description:
Measure:Objective response rate (ORR) by immune-related RECIST criteria (irRC)
Time Frame:2 years
Safety Issue:
Description:
Measure:Surgical resectability rate of borderline resectable pancreatic cancer (BRPC)
Time Frame:2 years
Safety Issue:
Description:
Measure:Pathologic response rate of patients with BRPC
Time Frame:2 years
Safety Issue:
Description:
Measure:Progression free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • Pancreas vaccine
  • immunotherapy
  • antibody
  • PD-1
  • IMC-CS4
  • Pembrolizumab
  • GVAX
  • Borderline Resectable

Last Updated