Clinical Trials /

Study of Pembrolizumab With or Without Defactinib Following Chemotherapy as a Neoadjuvant and Adjuvant Treatment for Resectable Pancreatic Ductal Adenocarcinoma

NCT03727880

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.

Related Conditions:
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
PembrolizumabMK-3475, KeytrudaArm A - Pembrolizumab and Defactinib
DefactinibArm 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

NameTypeDescriptionInterventions
Arm A - Pembrolizumab and DefactinibExperimental
  • Pembrolizumab
  • Defactinib
Arm B - PembrolizumabExperimental
  • Pembrolizumab

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 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 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:100 Years
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
Measure:Near pathologic complete response (pCR) rate
Time Frame:4 years
Safety Issue:
Description:Percent of subjects with a near 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).
Measure:Grade 3 pathologic response rate
Time Frame:4 years
Safety Issue:
Description:Percent of subjects with a grade 3 pathologic response 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).

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

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