Immunologic Effects of CDX-301 and CDX-1140 in Resectable Pancreatic Cancer Patients
Primary Purpose
Pancreatic Cancer, Cancer of the Pancreas, Pancreas Cancer
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CDX-301
CDX-1140
Research blood draw
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed surgically resectable pancreatic ductal adenocarcinoma, but not adenosquamous/squamous pancreas cancers (as determined by operating surgeon or tumor board). Patients who have previously received chemotherapy for his/her pancreas cancer within the past 6 months and who are now deemed resectable are also eligible for this trial.
- At least 18 years of age.
- ECOG performance status ≤ 1
Normal bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1,500 /cumm
- Platelets ≥ 100,000 /cumm
- Hemoglobin ≥ 9.0 g/dL
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
- Creatinine clearance ≤ 1.5 x IULN or glomerular filtration rate of ≥ 60 mL/min
- INR ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
- aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
- Albumin ≥ 3.0mg/dL
- The effects of CDX-301 and CDX-1140 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 3 months after the last dose of either study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study or for 3 months after the last dose of either study drug, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
- Immune deficiencies such as HIV.
- A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
- Currently receiving any other investigational agents or has received any other investigational agents within 4 weeks or 5 half-lives of the planned first dose of study treatment.
- Receipt of chemotherapy within 2 weeks of planned first dose of study treatment.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to CDX-301 or CDX-1140 or other agents used in the study.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (for > 1 month of 10 mg prednisone daily, or equivalent) or any other form of immunosuppressive therapy not routinely associated with chemotherapeutic regimen.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, immunosuppression, autoimmune conditions, or underlying pulmonary disease.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, immunosuppression, autoimmune conditions, or underlying pulmonary disease.
- Has an autoimmune disease requiring systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected).
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Has a known history of active TB (bacillus tuberculosis).
- Major surgery within 28 days prior to the first study treatment.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
- History of bone marrow or solid organ transplant.
- Patients with a history of myocardial infarction, cerebral vascular accident, thrombosis or pulmonary embolus within 12 months prior to the first dose of study treatment are excluded from this study.
- Patients with known mutations/amplifications in Flt3
Sites / Locations
- Washington University School of MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
CDX-1140 Monotherapy
CDX-1140 + CDX-301
Arm Description
Patients randomized to the CDX-1140 monotherapy arm will receive a single IV infusion at a dose of 1.5 mg/kg, with surgery to follow 7-12 days after administration of CDX-1140.
Patients randomized to the CDX-301 + CDX-1140 arm will receive CDX-301 at 75 mcg/kg/day as a subcutaneous injection every day for 5 days (Days 1-5) with CDX-1140 IV at 1.5 mg/kg on Day 8 +/-1 day. Surgery will be 7-12 days after administration of CDX-1140.
Outcomes
Primary Outcome Measures
Amount of intratumoral conventional dendritic cells (cDCs)
Secondary Outcome Measures
Full Information
NCT ID
NCT04536077
First Posted
August 27, 2020
Last Updated
January 17, 2023
Sponsor
Washington University School of Medicine
Collaborators
Celldex Therapeutics, The Foundation for Barnes-Jewish Hospital, National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT04536077
Brief Title
Immunologic Effects of CDX-301 and CDX-1140 in Resectable Pancreatic Cancer Patients
Official Title
Testing the Immunologic Effects of CDX-301 and CDX-1140 in Resectable Pancreatic Cancer Patients
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 25, 2021 (Actual)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
Celldex Therapeutics, The Foundation for Barnes-Jewish Hospital, National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The central hypothesis is that the addition of CDX-301 to CDX-1140 radically improves anti-tumor immunity in patients with pancreatic ductal adenocarcinoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer, Cancer of the Pancreas, Pancreas Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CDX-1140 Monotherapy
Arm Type
Experimental
Arm Description
Patients randomized to the CDX-1140 monotherapy arm will receive a single IV infusion at a dose of 1.5 mg/kg, with surgery to follow 7-12 days after administration of CDX-1140.
Arm Title
CDX-1140 + CDX-301
Arm Type
Experimental
Arm Description
Patients randomized to the CDX-301 + CDX-1140 arm will receive CDX-301 at 75 mcg/kg/day as a subcutaneous injection every day for 5 days (Days 1-5) with CDX-1140 IV at 1.5 mg/kg on Day 8 +/-1 day. Surgery will be 7-12 days after administration of CDX-1140.
Intervention Type
Drug
Intervention Name(s)
CDX-301
Intervention Description
The drug will be supplied free of charge by Celldex
Intervention Type
Drug
Intervention Name(s)
CDX-1140
Intervention Description
The drug will be supplied free of charge by Celldex
Intervention Type
Procedure
Intervention Name(s)
Research blood draw
Intervention Description
At screening; prior to first therapeutic dose of CDX-1140, on the day of the infusion; and at the time of surgery
Primary Outcome Measure Information:
Title
Amount of intratumoral conventional dendritic cells (cDCs)
Time Frame
At time of surgery (estimated to be between day 8 and day 20)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed surgically resectable pancreatic ductal adenocarcinoma, but not adenosquamous/squamous pancreas cancers (as determined by operating surgeon or tumor board). Patients who have previously received chemotherapy for his/her pancreas cancer within the past 6 months and who are now deemed resectable are also eligible for this trial.
At least 18 years of age.
ECOG performance status ≤ 1
Normal bone marrow and organ function as defined below:
Absolute neutrophil count ≥ 1,500 /cumm
Platelets ≥ 100,000 /cumm
Hemoglobin ≥ 9.0 g/dL
AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
Creatinine clearance ≤ 1.5 x IULN or glomerular filtration rate of ≥ 60 mL/min
INR ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
Albumin ≥ 3.0mg/dL
The effects of CDX-301 and CDX-1140 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 3 months after the last dose of either study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study or for 3 months after the last dose of either study drug, she must inform her treating physician immediately.
Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
Immune deficiencies such as HIV.
A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
Currently receiving any other investigational agents or has received any other investigational agents within 4 weeks or 5 half-lives of the planned first dose of study treatment.
Receipt of chemotherapy within 2 weeks of planned first dose of study treatment.
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to CDX-301 or CDX-1140 or other agents used in the study.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (for > 1 month of 10 mg prednisone daily, or equivalent) or any other form of immunosuppressive therapy not routinely associated with chemotherapeutic regimen.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, immunosuppression, autoimmune conditions, or underlying pulmonary disease.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, immunosuppression, autoimmune conditions, or underlying pulmonary disease.
Has an autoimmune disease requiring systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected).
Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
Has a known history of active TB (bacillus tuberculosis).
Major surgery within 28 days prior to the first study treatment.
Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
History of bone marrow or solid organ transplant.
Patients with a history of myocardial infarction, cerebral vascular accident, thrombosis or pulmonary embolus within 12 months prior to the first dose of study treatment are excluded from this study.
Patients with known mutations/amplifications in Flt3
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
William G Hawkins, M.D.
Phone
314-362-7046
Email
hawkinsw@wustl.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William G Hawkins, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
William G Hawkins, M.D.
Phone
314-362-7046
Email
hawkinsw@wustl.edu
First Name & Middle Initial & Last Name & Degree
William G Hawkins, M.D.
First Name & Middle Initial & Last Name & Degree
David DeNardo, Ph.D.
First Name & Middle Initial & Last Name & Degree
Ryan Fields, M.D.
First Name & Middle Initial & Last Name & Degree
Kian-Huat Lim, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Olivia Aranha, M.D.
First Name & Middle Initial & Last Name & Degree
Nusayba Bagegni, M.D.
First Name & Middle Initial & Last Name & Degree
Salman Chaudhry, M.D.
First Name & Middle Initial & Last Name & Degree
Patrick Grierson, M.D.
First Name & Middle Initial & Last Name & Degree
Tanner Johanns, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Peter Oppelt, M.D.
First Name & Middle Initial & Last Name & Degree
Katrina Pedersen, M.D.
First Name & Middle Initial & Last Name & Degree
Rama Suresh, M.D.
First Name & Middle Initial & Last Name & Degree
Benjamin Tan, M.D.
First Name & Middle Initial & Last Name & Degree
Nikolaos Trikalinos, M.D.
First Name & Middle Initial & Last Name & Degree
Liang-I Kang, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Caron Rigden, M.D.
First Name & Middle Initial & Last Name & Degree
Katherine Navo, MSN
First Name & Middle Initial & Last Name & Degree
Samuel Ballentine, M.D.
First Name & Middle Initial & Last Name & Degree
William Chapman, M.D.
First Name & Middle Initial & Last Name & Degree
Maria Bernadette Doyle, M.D.
First Name & Middle Initial & Last Name & Degree
Adeel Khan, M.D.
First Name & Middle Initial & Last Name & Degree
Dominic Sanford, M.D.
First Name & Middle Initial & Last Name & Degree
Natasha Leigh, M.D.
First Name & Middle Initial & Last Name & Degree
Crystal Wolf, M.S.
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
Learn more about this trial
Immunologic Effects of CDX-301 and CDX-1140 in Resectable Pancreatic Cancer Patients
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