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Trial record 10 of 1598 for:    Pancreatic Cancer | United States

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

Tracking Information
First Submitted Date  ICMJE May 20, 2015
First Posted Date  ICMJE May 22, 2015
Last Update Posted Date April 5, 2019
Study Start Date  ICMJE February 2016
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2015)
Median IL17A expression in vaccine-induced lymphoid aggregates found in surgically resected pancreatic tumors [ Time Frame: 4 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02451982 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2015)
  • Number of participants experiencing immune-related toxicities (IRAEs) [ Time Frame: 4 years ]
  • Overall Survival [ Time Frame: 4 years ]
  • Disease Free Survival [ Time Frame: 4 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neoadjuvant/Adjuvant GVAX Pancreas Vaccine (With CY) With or Without Nivolumab and Urelumab Trial for Surgically Resectable Pancreatic Cancer
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Cyclophosphamide
    • Biological: GVAX pancreatic cancer
  • 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.
    Interventions:
    • Drug: Cyclophosphamide
    • Biological: GVAX pancreatic cancer
    • Drug: Nivolumab
  • 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.
    Interventions:
    • Drug: Cyclophosphamide
    • Biological: GVAX pancreatic cancer
    • Drug: Nivolumab
    • Drug: Urelumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 24, 2018)
75
Original Estimated Enrollment  ICMJE
 (submitted: May 20, 2015)
50
Estimated Study Completion Date  ICMJE February 2023
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Carol Judkins, RN 410-614-5241 judkica@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02451982
Other Study ID Numbers  ICMJE J1568
IRB00050517 ( Other Identifier: JHMIRB )
R01CA197296 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Lei Zheng, MD, PhD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP