Clinical trial NCT03727880: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Resectable Pancreatic Ductal Adenocarcinoma (PDAC)
Pancreatic Ductal Adenocarcinoma
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
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Verastem, Inc.
First posted: 2018-11-01
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Pathologic complete response (pCR) rate
timeFrame: 4 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 4 years
measure: Disease free survival (DFS)
timeFrame: 4 years
measure: Number of participants experiencing study drug-related toxicities
timeFrame: 4 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Samuel Oschin Cancer Center at Cedars-Sinai
state: California
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: San Antonio
country: United States
facility: The University of Texas Health Science Center San Antonio
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center San Antonio
name: Lei Zheng, MD
role: PRINCIPAL_INVESTIGATOR
References: