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

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ClinicalTrials.gov Identifier: NCT03727880
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : July 4, 2019
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Verastem, Inc.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Resectable Pancreatic Ductal Adenocarcinoma (PDAC) Pancreatic Ductal Adenocarcinoma Drug: Pembrolizumab Drug: Defactinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : May 28, 2019
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A - Pembrolizumab and Defactinib Drug: Pembrolizumab
Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart.
Other Names:
  • MK-3475
  • Keytruda

Drug: Defactinib
Following 2 cycles of standard of care neoadjuvant chemotherapy, subjects will receive 100 mg defactinib twice a day up until 2 days preceding their surgery (approximately 6 weeks) during the immunotherapy cycles with pembrolizumab. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 100mg defactinib twice a day for 24 weeks.

Experimental: Arm B - Pembrolizumab Drug: Pembrolizumab
Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart.
Other Names:
  • MK-3475
  • Keytruda




Primary Outcome Measures :
  1. Pathologic complete response (pCR) rate [ Time Frame: 4 years ]
    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 :
  1. Overall survival (OS) [ Time Frame: 4 years ]
    Number of months until death

  2. Disease free survival (DFS) [ Time Frame: 4 years ]
    Number of months until disease recurrence

  3. Number of participants experiencing study drug-related toxicities [ Time Frame: 4 years ]
    Number of participants experiencing drug-related adverse events as defined by CTCAE v5.0

  4. Near pathologic complete response (pCR) rate [ Time Frame: 4 years ]
    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).

  5. Grade 3 pathologic response rate [ Time Frame: 4 years ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03727880


Contacts
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Contact: Susan Sartorius-Mergenthaler, RN 410-614-3644 Sartosu@jhmi.edu

Locations
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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Susan Sartorius-Mergenthaler, RN    410-614-3644    Sartosu@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Merck Sharp & Dohme Corp.
Verastem, Inc.
Investigators
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Principal Investigator: Lei Zheng, MD Johns Hopkins Medical Institution
Principal Investigator: Arsen Osipov, MD Johns Hopkins Medical Institution

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03727880     History of Changes
Other Study ID Numbers: J18140
IRB00182490 ( Other Identifier: JHMI IRB )
First Posted: November 1, 2018    Key Record Dates
Last Update Posted: July 4, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
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

Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents