Platform Study of Neoadjuvant and Adjuvant Immunotherapy for Patients With Resectable Adenocarcinoma of the Pancreas

Pancreatic Cancer Clinical Trial

Official title:

A Platform Study of Combination Immunotherapy for the Neoadjuvant and Adjuvant Treatment of Patients With Surgically Resectable Adenocarcinoma of the Pancreas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02451982
• Other study ID #: J1568
• Secondary ID: IRB00050517R01CA
• Status: Recruiting
• Phase: Phase 2
• Start date: March 28, 2016
• Est. completion date: December 31, 2025

Study information

• Verified date: August 2023
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: Carol Judkins, RN
• Phone: 410-614-5241
• Email: judkica[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This platform trial will evaluate various immunotherapy combinations given in the neo-adjuvant and adjuvant setting in patients with surgically resectable pancreatic ductal adenocarcinoma.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 76
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Newly diagnosed or clinically-suspected adenocarcinoma of the head, neck, or uncinate process of the pancreas
• Tumor must be surgically resectable
• ECOG Performance Status of 0 to 1
• Adequate organ function as defined by study-specified laboratory tests
• Must agree to use acceptable form of birth control

Exclusion Criteria:

• Received any type of anti-cancer treatment or immunotherapy for pancreas cancer
• History of autoimmune disease (Graves or Hashimoto's disease, vitiligo, and type I diabetes are allowed)
• Systemically steroid use within 14 days
• Evidence of active infection
• Pregnant or lactating
• Diagnosed with another cancer or myeloproliferative disorder (some exceptions)
• History of severe hypersensitivity reaction to any monoclonal antibody or known component of the study drugs
• Known history of infection with HIV, hepatitis B, or hepatitis C
• Oxygen saturation of <92% on room air by pulse oximetry
• On home oxygen

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Cancer

Intervention

Drug:
• Cyclophosphamide
200 mg/m2 IV

Biological:
• GVAX pancreatic cancer
5x10^8 cells intradermal injection

Drug:
• Nivolumab
480 mg IV
• Urelumab
8 mg IV
• BMS-986253
2400 mg IV

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Bristol-Myers Squibb, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IL17A expression	median IL17A expression in lymphoid aggregates from resected tumor (Arms A and B only)	4 years
Primary	Intratumoral CD8+CD137+cells	Fold change of intratumoral CD8+CD137+cells before and after neoadjuvant therapy (Arms B and C only)	4 years
Primary	Intratumoral granzyme B+PD-1+CD137+ cells	Percent change of intratumoral granzyme B+PD-1+CD137+ cells in surgical (post-treatment) tissue compared to baseline (pre-treatment) biopsy (Arm D only)	4 years
Primary	Pathologic Response	Percent of patients with a response grade of 0-2 (0=complete response 1=marked response, 2=moderate response) at time of surgery	4 years
Secondary	Drug-Related Adverse Events	Number of participants experiencing study drug-related toxicities	4 years
Secondary	Overall Survival	Overall Survival is defined as the time from surgery to death from any cause	4 years
Secondary	Disease Free Survival	Disease Free Survival is defined as the time from surgery until evidence of disease recurrence or death from any cause	4 years