Clinical Trial: NCT02451982 - My Cancer Genome

NCT02451982

Description:

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.

Related Conditions:

Pancreatic Adenocarcinoma

Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT02451982

Trial Eligibility

Document

Title

Brief Title: Neoadjuvant/Adjuvant GVAX Pancreas Vaccine (With CY) With or Without Nivolumab Trial for Surgically Resectable Pancreatic Cancer
Official Title: A Randomized Study of a GM-CSF Secreting Allogeneic Pancreatic Cancer Vaccine With Our Without a PD-1 Blockade Antibody (Nivolumab) for the Neoadjuvant and Adjuvant Treatment of Patients With Surgically Resectable Adenocarcinoma of the Pancreas

Clinical Trial IDs

ORG STUDY ID: J1568
SECONDARY ID: IRB00050517
NCT ID: NCT02451982

Conditions

Pancreatic Cancer

Interventions

Drug	Synonyms	Arms
Cyclophosphamide	Cytoxan, CY	Arm A: CY/GVAX alone
GVAX pancreatic cancer	GVAX, pancreatic tumor vaccine	Arm A: CY/GVAX alone
Nivolumab	OPDIVO; BMS-936558; anti-PD1	Arm B: CY/GVAX with nivolumab

Purpose

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.

Trial Arms

Name	Type	Description	Interventions
Arm A: CY/GVAX alone	Experimental	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.	Cyclophosphamide
Arm B: CY/GVAX with nivolumab	Experimental	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.	Cyclophosphamide Nivolumab

Eligibility 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

Maximum Eligible Age:	100 Years
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Median IL17A expression in vaccine-induced lymphoid aggregates found in surgically resected pancreatic tumors
Time Frame:	4 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:	Number of participants experiencing immune-related toxicities (IRAEs)
Time Frame:	4 years
Safety Issue:
Description:

Measure:	Overall Survival
Time Frame:	4 years
Safety Issue:
Description:

Measure:	Disease Free Survival
Time Frame:	4 years
Safety Issue:
Description:

Details

Phase:	Phase 1/Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Sidney Kimmel Comprehensive Cancer Center

Last Updated

January 11, 2017

Clinical Trials /

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