Description:
This study will test the effectiveness (anti-tumor activity), safety, and ability to increase
the body's immune system to fight pancreatic cancer by combining standard chemotherapy before
and after surgery, with study drug PD-1 antibody, pembrolizumab, with and without study drug,
focal adhesion kinase inhibitor (FAK), defactinib, in people with "high risk" resectable
(surgically removable) pancreatic cancer. The purpose of this study is to evaluate if
reprograming the tumor microenvironment by targeting FAK following chemotherapy can
potentiate anti-programmed death-1 (PD-1) antibody.
Title
- Brief Title: Study of Pembrolizumab With or Without Defactinib Following Chemotherapy as a Neoadjuvant and Adjuvant Treatment for Resectable Pancreatic Ductal Adenocarcinoma
- Official Title: A Randomized Phase II Study of Pembrolizumab With or Without Defactinib, a Focal Adhesion Kinase Inhibitor Following Chemotherapy as a Neoadjuvant and Adjuvant Treatment for Resectable Pancreatic Ductal Adenocarcinoma (PDAC)
Clinical Trial IDs
- ORG STUDY ID:
J18140
- SECONDARY ID:
IRB00182490
- NCT ID:
NCT03727880
Conditions
- Resectable Pancreatic Ductal Adenocarcinoma (PDAC)
- Pancreatic Ductal Adenocarcinoma
Interventions
Drug | Synonyms | Arms |
---|
Pembrolizumab | MK-3475, Keytruda | Arm A - Pembrolizumab and Defactinib |
Defactinib | | Arm A - Pembrolizumab and Defactinib |
Purpose
This study will test the effectiveness (anti-tumor activity), safety, and ability to increase
the body's immune system to fight pancreatic cancer by combining standard chemotherapy before
and after surgery, with study drug PD-1 antibody, pembrolizumab, with and without study drug,
focal adhesion kinase inhibitor (FAK), defactinib, in people with "high risk" resectable
(surgically removable) pancreatic cancer. The purpose of this study is to evaluate if
reprograming the tumor microenvironment by targeting FAK following chemotherapy can
potentiate anti-programmed death-1 (PD-1) antibody.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A - Pembrolizumab and Defactinib | Experimental | | |
Arm B - Pembrolizumab | Experimental | | |
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years.
- Has pancreatic ductal adenocarcinoma
- Has resectable disease at the time of diagnosis
- Has not received any systemic therapy for pancreatic ductal adenocarcinoma
- Has stage ≤ IIb disease at time of diagnosis and enrollment
- Elevated tumor marker, CA (carbohydrate antigen) 19-9 >200
- ECOG performance status 0 or 1
- Patient must have adequate organ function defined by the study-specified laboratory
tests.
- Must use acceptable form of birth control while on study.
- Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria:
Patients who have received any prior chemotherapy, radiotherapy or investigational agents
for pancreatic cancer.
- Patients who have received prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2,
anti-CTLA-4, or with an agent directed to another stimulatory or co-inhibitory T-cell
receptor (e.g., CTLA-4, OX 40, CD137).
- Has received prior therapy with FAK inhibitor.
- Woman who are pregnant or breastfeeding.
- Have received a live vaccine or live-attenuated vaccine within 30 days prior to study
drug.
- Is currently or has participated in another investigational study within 4 weeks prior
to receiving study drug.
- History or current use of immunosuppressive medications within 7 days prior to study
medications.
- Has a known additional malignancy that is progressing or has required active treatment
within the past 2 years or that is expected to require active treatment within two
years.
- Has active autoimmune disease that has required systemic treatment in the past 2
years.
- Has a history of (non-infectious) pneumonitis/interstitial lung disease or current
pneumonitis.
- Has an active infection requiring systemic therapy.
- Infection with HIV or hepatitis B or C.
- Patient with uncontrolled intercurrent illness including, but not limited to,
uncontrolled infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements.
- Known allergy or hypersensitivity to the study drugs.
- Received any growth factors including, but not limited to, granulocyte-colony
stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of study drug
administration.
- Has history of any organ transplant, including corneal transplants.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Pathologic complete response (pCR) rate |
Time Frame: | 4 years |
Safety Issue: | |
Description: | Percent of subjects with a pathologic complete response (pCR) per the tumor regression grade scores established by the College of American Pathologist: Grade 0= complete response (no viable cancer cells), Grade 1= near complete response (single cells or rare small groups of cancer cells), Grade 2= partial response (residual tumor with evidence of regression), or Grade 3= no response (extensive residual tumor with no evidence of regression). |
Secondary Outcome Measures
Measure: | Overall survival (OS) |
Time Frame: | 4 years |
Safety Issue: | |
Description: | Number of months until death |
Measure: | Disease free survival (DFS) |
Time Frame: | 4 years |
Safety Issue: | |
Description: | Number of months until disease recurrence |
Measure: | Number of participants experiencing study drug-related toxicities |
Time Frame: | 4 years |
Safety Issue: | |
Description: | Number of participants experiencing drug-related adverse events as defined by CTCAE v5.0 |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Trial Keywords
- Pembrolizumab
- Defactinib
- Immunotherapy
- Anti-PD-1
- Antibody
- PD-L1
- Pancreatic cancer
- Neoadjuvant chemotherapy
- Adjuvant chemotherapy
- PDAC - Pancreatic Ductal Adenocarcinoma
- FAK (focal adhesion kinase) inhibitor
- Resectable Pancreatic Adenocarcinoma
- High Risk Resectable Pancreatic Cancer
- Tumor microenvironment
- CA 19-9
- Surgery
- Pancreatectomy
Last Updated
August 20, 2021