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Neoadjuvant/Adjuvant GVAX Pancreas Vaccine (With CY) With or Without Nivolumab and Urelumab Trial for Surgically Resectable Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT02451982
Recruitment Status : Recruiting
First Posted : May 22, 2015
Last Update Posted : April 5, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
This study will be looking at whether CY/GVAX with nivolumab is more effective than CY/GVAX alone in altering the pancreatic tumor microenvironment (IL17 expression) to aid in the anti-tumor response.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: Cyclophosphamide Biological: GVAX pancreatic cancer Drug: Nivolumab Drug: Urelumab Phase 1 Phase 2

Detailed Description:
Immunotherapy is an innovative approach being developed for the treatment of pancreatic cancer, a lethal and relatively chemotherapy-resistant disease. However, the tumor and its environment have developed a number of ways in which they inhibit the function of the immune system preventing it from recognizing and killing the cancer. In addition, the investigators still do not understand how T cells, the cells in the immune system that have the potential to recognize cancer as different and kill cancer cells, traffic into the tumor to accomplish their task. The investigators are currently testing an immune system activating pancreatic cancer vaccine (known as GVAX) in combination with immune boosting doses of the chemotherapy agent, cyclophosphamide, as preoperative and postoperative treatments for pancreatic cancer. The investigators have discovered tertiary lymphoid aggregates, a unique lymph node-like structure formed within resected tumors from the patients who received the vaccine two weeks prior to the surgery. This discovery demonstrates that the immune system can get into the tumor and provides the investigators with the opportunity to better understand how these immune cells traffic into the tumor and function once they arrive. The investigators also found that the vaccine causes an increase in signals that would suppress the immune system's ability to fight off cancer cells, including signals involving PD-1. In this novel study, the investigators will test the effects of blocking PD-1 in combination with the vaccine in patients with pancreatic cancer. The investigators will specifically isolate these immune cells and evaluate at both the genetic and protein level, the types of signals expressed by these aggregates. The investigators will compare aggregates from patients with long term survival versus patients who succumb to their cancer early. In this way, the investigators will be able to determine how safe this novel treatment is, how effective it is at changing the immune system in pancreatic cancer, and how it impacts the health and survival of pancreatic cancer patients who undergo surgery to remove the cancer.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Study of a GM-CSF Secreting Allogeneic Pancreatic Cancer Vaccine With or Without a PD-1 Blockade Antibody (Nivolumab) and CD137 Agonist Antibody (Urelumab) for the Neoadjuvant and Adjuvant Treatment of Patients With Surgically Resectable Adenocarcinoma of the Pancreas
Study Start Date : February 2016
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : February 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Arm A: CY/GVAX alone
Patients receive low-dose cyclophosphamide IV on day 0 and GVAX pancreatic cancer vaccine ID on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide IV on day 0 and the vaccine on day 1. Beginning approximately 1 month after vaccination, patients receive standard adjuvant chemoradiotherapy. Beginning approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive low-dose cyclophosphamide IV on day 0 and the vaccine on day 1. Treatment with cyclophosphamide and the vaccine repeats every 28 days for 4 courses. Patients will then enter the extended treatment phase where they will receive cyclophosphamide on day 0, and GVAX on day 1 every 12 weeks for another 2 treatments.
Drug: Cyclophosphamide
200 mg/m2
Other Name: Cytoxan, CY

Biological: GVAX pancreatic cancer
5x10^8 cells
Other Name: GVAX, pancreatic tumor vaccine

Experimental: Arm B: CY/GVAX with nivolumab
Patients receive low-dose cyclophosphamide and nivolumab IV on day 0 and GVAX pancreatic cancer vaccine ID on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide and nivolumab IV on day 0 and the vaccine on day 1. Beginning approximately 1 month after vaccination, patients receive standard adjuvant chemoradiotherapy. Beginning approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive low-dose cyclophosphamide and nivolumab IV on day 0 and the vaccine on day 1. Treatment with cyclophosphamide, nivolumab, and the vaccine repeats every 28 days for 4 courses. Patients will then enter the extended treatment phase where they will receive nivolumab every 4 weeks for another 6 treatments as well as cyclophosphamide on day 0, and GVAX on day 1 every 12 weeks for another 2 treatments.
Drug: Cyclophosphamide
200 mg/m2
Other Name: Cytoxan, CY

Biological: GVAX pancreatic cancer
5x10^8 cells
Other Name: GVAX, pancreatic tumor vaccine

Drug: Nivolumab
480 mg
Other Name: OPDIVO; BMS-936558; anti-PD1

Experimental: Arm C: CY/GVAX with nivolumab and urelumab
Patients receive low-dose cyclophosphamide, nivolumab, and urelumab IV on day 0 and GVAX pancreatic cancer vaccine ID on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide, nivolumab, and urelumab on day 0 and the vaccine on day 1. Beginning approximately 28 days after vaccination, patients receive standard adjuvant chemoradiotherapy. Beginning approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive low-dose cyclophosphamide, nivolumab, and urelumab on day 0 and GVAX on day 1. Treatment with cyclophosphamide, nivolumab, urelumab, and the vaccine repeats every 28 days for 4 courses. Patients will then enter the extended treatment phase where they will receive nivolumab and urelumab every 4 weeks for another 6 treatments as well as cyclophosphamide on day 0, and GVAX on day 1 every 12 weeks for another 2 treatments.
Drug: Cyclophosphamide
200 mg/m2
Other Name: Cytoxan, CY

Biological: GVAX pancreatic cancer
5x10^8 cells
Other Name: GVAX, pancreatic tumor vaccine

Drug: Nivolumab
480 mg
Other Name: OPDIVO; BMS-936558; anti-PD1

Drug: Urelumab
8 mg
Other Name: BMS-663513; anti-CD137 Agonist




Primary Outcome Measures :
  1. Median IL17A expression in vaccine-induced lymphoid aggregates found in surgically resected pancreatic tumors [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Number of participants experiencing immune-related toxicities (IRAEs) [ Time Frame: 4 years ]
  2. Overall Survival [ Time Frame: 4 years ]
  3. Disease Free Survival [ Time Frame: 4 years ]


Information from the National Library of Medicine

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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:

  1. Newly diagnosed adenocarcinoma of the head, neck, or uncinate process of the pancreas

    • Stage I or II disease
  2. Surgically resectable disease (R0 or R1) by spiral CT scan

    • No distant metastases
  3. ECOG Performance Status of 0 to 1
  4. Adequate organ function as defined by study-specified laboratory tests
  5. Must use acceptable form of birth control
  6. Signed informed consent form
  7. Willing and able to comply with study procedures

Exclusion Criteria:

  1. Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune, psychological or other medical conditions
  2. Patients with 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)
  3. Patients who 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)
  4. Patients who have received therapy for pancreatic cancer
  5. Using systemically active steroid use
  6. Patients who have known history of infection with HIV, hepatitis B, or hepatitis C
  7. Patients on home oxygen
  8. Patients with oxygen saturation of <92% on room air by pulse oximetry
  9. Pregnant or lactating
  10. Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures

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): NCT02451982


Contacts
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Contact: Carol Judkins, RN 410-614-5241 judkica@jhmi.edu

Locations
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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce    410-955-8804    jhcccro@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
Bristol-Myers Squibb
Investigators
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Principal Investigator: Lei Zheng, MD, PhD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02451982     History of Changes
Other Study ID Numbers: J1568
IRB00050517 ( Other Identifier: JHMIRB )
R01CA197296 ( U.S. NIH Grant/Contract )
First Posted: May 22, 2015    Key Record Dates
Last Update Posted: April 5, 2019
Last Verified: April 2019
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Cyclophosphamide
Nivolumab
Pancrelipase
Vaccines
Antibodies, Monoclonal
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