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

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ClinicalTrials.gov Identifier: NCT03153410
Recruitment Status : Recruiting
First Posted : May 15, 2017
Last Update Posted : March 19, 2019
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Eli Lilly and Company
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: Cyclophosphamide Drug: GVAX Drug: Pembrolizumab Drug: IMC-CS4 Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 7, 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cyclophosphamide, GVAX, Pembrolizumab and IMC-CS4 Drug: Cyclophosphamide

200 mg/m2 is to be administered as a 30 minute IV infusion one day prior to GVAX for a total of 8 doses.

Other Names:

Cytoxan CY

Other Name: CY

Drug: GVAX

5E8 cells is to be administered one day after CY, pembrolizumab, and IMC-CS4/ LY3022855 for a total of eight doses.

Other Names:

Pancreatic cancer vaccine Panc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-Neo

Other Name: Panc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-Neo

Drug: Pembrolizumab

200 mg will be administered as a 30 minute IV infusion one day prior to the GVAX pancreas vaccine for a total of 18 doses.

Other Names:

MK-3475 KEYTRUDA

Other Name: MK-3475, KEYTRUDA®

Drug: IMC-CS4
75 mg for dose level 1 and 100 mg at dose level 2 will be administered (Day 1, Day 8 and Day 15) as a 30 minute(s) IV infusion one day prior to GVAX pancreas vaccine for a total 18 doses.
Other Name: LY3022855




Primary Outcome Measures :
  1. CD8 T cell density in the primary tumor after neoadjuvant administration of combination immunotherapy by immunohistochemistry (IHC) [ Time Frame: 2 years ]
  2. Number of participants experiencing study drug-related toxicities [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 2 years ]
  2. Disease free survival (DFS) [ Time Frame: 2 years ]
  3. Objective response rate (ORR) by immune-related RECIST criteria (irRC) [ Time Frame: 2 years ]
  4. Surgical resectability rate of borderline resectable pancreatic cancer (BRPC) [ Time Frame: 2 years ]
  5. Pathologic response rate of patients with BRPC [ Time Frame: 2 years ]
  6. Progression free survival (PFS) [ Time Frame: 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03153410


Contacts
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Contact: Susan Sartorius-Mergenthaler, RN 410-614-3644 sartosu@jhmi.edu
Contact: Jane Zorzi, RN 410-614-5818 jzorzi1@jhmi.edu

Locations
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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Ana DeJesus, MD    443-287-0411    adejesu1@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Merck Sharp & Dohme Corp.
Eli Lilly and Company
Investigators
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Principal Investigator: Ana DeJesus, MD Johns Hopkins University

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03153410     History of Changes
Other Study ID Numbers: J1766
IRB00130267 ( Other Identifier: JHMIRB )
First Posted: May 15, 2017    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Pancreas vaccine
immunotherapy
antibody
PD-1
IMC-CS4
Pembrolizumab
GVAX
Borderline Resectable
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Carcinoma
Cyclophosphamide
Pembrolizumab
Pancrelipase
Pancreatin
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Gastrointestinal Agents