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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03727880
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : January 6, 2020
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Verastem, Inc.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE October 31, 2018
First Posted Date  ICMJE November 1, 2018
Last Update Posted Date January 6, 2020
Actual Study Start Date  ICMJE May 28, 2019
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 31, 2018)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 2, 2020)
  • Overall survival (OS) [ Time Frame: 4 years ]
    Number of months until death
  • Disease free survival (DFS) [ Time Frame: 4 years ]
    Number of months until disease recurrence
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2018)
  • Overall survival (OS) [ Time Frame: 4 years ]
    Number of months until death
  • Disease free survival (DFS) [ Time Frame: 4 years ]
    Number of months until disease recurrence
  • 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
  • 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).
  • 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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pembrolizumab With or Without Defactinib Following Chemotherapy as a Neoadjuvant and Adjuvant Treatment for Resectable Pancreatic Ductal Adenocarcinoma
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Resectable Pancreatic Ductal Adenocarcinoma (PDAC)
  • Pancreatic Ductal Adenocarcinoma
Intervention  ICMJE
  • 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 400 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 400mg defactinib twice a day for 24 weeks.
Study Arms  ICMJE
  • Experimental: Arm A - Pembrolizumab and Defactinib
    Interventions:
    • Drug: Pembrolizumab
    • Drug: Defactinib
  • Experimental: Arm B - Pembrolizumab
    Intervention: Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 31, 2018)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2023
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Susan Sartorius-Mergenthaler, RN 410-614-3644 Sartosu@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03727880
Other Study ID Numbers  ICMJE J18140
IRB00182490 ( Other Identifier: JHMI IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE
  • Merck Sharp & Dohme Corp.
  • Verastem, Inc.
Investigators  ICMJE
Principal Investigator: Lei Zheng, MD Johns Hopkins Medical Institution
Principal Investigator: Arsen Osipov, MD Johns Hopkins Medical Institution
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP