Clinical Trials /

Phase II Trial of Neoadjuvant Pembrolizumab for Patients With Early Stage Gastroesophageal Adenocarcinoma

NCT04089904

Description:

To determine the pathologic complete response (pCR) rate in patients with cT1b-T2N0 GEA treated with neoadjuvant pembrolizumab followed by surgical resection.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Trial of Neoadjuvant Pembrolizumab for Patients With Early Stage Gastroesophageal Adenocarcinoma
  • Official Title: A Phase II Trial of Neoadjuvant Pembrolizumab for Resectable Early Stage Gastroesophageal Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: IRB19-0310
  • NCT ID: NCT04089904

Conditions

  • Gastroesophageal Junction Adenocarcinoma
  • Gastric Adenocarcinoma
  • Esophageal Adenocarcinoma

Interventions

DrugSynonymsArms
Pembrolizumab InjectionARM 1

Purpose

To determine the pathologic complete response (pCR) rate in patients with cT1b-T2N0 GEA treated with neoadjuvant pembrolizumab followed by surgical resection.

Trial Arms

NameTypeDescriptionInterventions
ARM 1Experimental
  • Pembrolizumab Injection

Eligibility Criteria

        Inclusion Criteria:

        Participants are eligible to be included in the study only if all of the following criteria
        apply:

          1. Male/female participants who are at least 18 years of age on the day of signing
             informed consent with histologically confirmed diagnosis of untreated esophageal
             adenocarcinoma (AC) (including Siewert type I and II esophagogastric junction AC) or
             gastric AC (including Siewert type III esophagogastric junction AC), with clinical
             stage T1b-T2, N0, and M0.

          2. Patients must undergo endoscopic ultrasound (EUS), CT chest/abdomen/pelvis with IV/PO
             contrast (MRI abdomen/pelvis plus noncontrast chest CT is acceptable if patient has a
             contraindication to iodinated dye), and PET/CT to complete staging and confirm absence
             of metastatic disease.

          3. HER2+ and HER2- patients, and all other known molecular subsets are eligible.

          4. Diagnostic laparoscopy is not mandated and can be performed as clinically indicated.

          5. Eligible for surgery with curative intent

          6. A female participant is eligible to participate if she is not pregnant (see Appendix
             3), not breastfeeding, and at least one of the following conditions applies:

               1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR

               2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the
                  treatment period and for at least 120 days after the last dose of study
                  treatment.

          7. The participant (or legally acceptable representative if applicable) provides written
             informed consent for the trial.

          8. Measurable or non-measurable disease by RECIST 1.1 will be allowed.

          9. Is willing to provide tissue for correlative studies from the primary tumor lesion at
             baseline and at time of surgery. Is willing to provide blood and stool samples for all
             ordered studies.

         10. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
             Evaluation of ECOG is to be performed within 7 days prior to the date of allocation.

         11. Have adequate organ function as defined in the following table (Table 1). Table 1
             Adequate Organ Function Laboratory Values System Laboratory Value Hematological

               -  Absolute neutrophil count (ANC) ≥1500/µL

               -  Platelets ≥100 000/µL

               -  Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La Renal

               -  Creatinine OR Measured or calculatedb creatinine clearance (GFR can also be used
                  in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with
                  creatinine levels >1.5 × institutional ULN Hepatic

               -  Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total
                  bilirubin levels >1.5 × ULN

               -  AST (SGOT) and ALT (SGPT) ≤2.5 × ULN Coagulation

               -  International normalized ratio (INR) OR prothrombin time (PT) Activated partial
                  thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving
                  anticoagulant therapy as long as PT or aPTT is within therapeutic range of
                  intended use of anticoagulants

        ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST
        (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular
        filtration rate; ULN=upper limit of normal.

          1. Criteria must be met without erythropoietin dependency and without packed red blood
             cell (pRBC) transfusion within last 2 weeks.

          2. Creatinine clearance (CrCl) should be calculated per institutional standard. Note:
             This table includes eligibility-defining laboratory value requirements for treatment;
             laboratory value requirements should be adapted according to local regulations and
             guidelines for the administration of specific chemotherapies.

        Exclusion Criteria:

          -  Participants are excluded from the study if any of the following criteria apply:

               1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to
                  allocation (see Appendix 3). If the urine test is positive or cannot be confirmed
                  as negative, a serum pregnancy test will be required.

               2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or
                  with an agent directed to another stimulatory or co-inhibitory T-cell receptor
                  (eg, CTLA-4, OX 40, CD137).

               3. Previous or concurrent malignancy, except for adequately treated basal cell or
                  squamous cell skin cancer, in situ cervical cancer, or any other cancer for which
                  the patient has been previously treated and the lifetime recurrence risk is less
                  than 30%.

               4. Has received prior systemic anti-cancer therapy including investigational agents
                  within 4 weeks prior to allocation.

                  Note: Participants must have recovered from all AEs due to previous therapies to
                  ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.

                  Note: If participant received major surgery, they must have recovered adequately
                  from the toxicity and/or complications from the intervention prior to starting
                  study treatment.

               5. Has received prior radiotherapy within 2 weeks of start of study treatment.
                  Participants must have recovered from all radiation-related toxicities, not
                  require corticosteroids, and not have had radiation pneumonitis.

               6. Has received a live vaccine within 30 days prior to the first dose of study drug.
                  Examples of live vaccines include, but are not limited to, the following:
                  measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies,
                  Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines
                  for injection are generally killed virus vaccines and are allowed; however,
                  intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are
                  not allowed.

               7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid
                  therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other
                  form of immunosuppressive therapy within 7 days prior to the first dose of study
                  drug.

               8. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
                  excipients.

               9. Has active autoimmune disease that has required systemic treatment in the past 2
                  years (i.e. with use of disease modifying agents, corticosteroids or
                  immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or
                  physiologic corticosteroid replacement therapy for adrenal or pituitary
                  insufficiency, etc.) is not considered a form of systemic treatment.

              10. Has a history of (non-infectious) pneumonitis that required steroids or has
                  current pneumonitis.

              11. Has an active infection requiring systemic therapy.

              12. Has a known history of Human Immunodeficiency Virus (HIV).

              13. Has a known history of active TB (Bacillus Tuberculosis).

              14. Has a history or current evidence of any condition, therapy, or laboratory
                  abnormality that might confound the results of the study, interfere with the
                  subject's participation for the full duration of the study, or is not in the best
                  interest of the subject to participate, in the opinion of the treating
                  investigator.

              15. Has known psychiatric or substance abuse disorders that would interfere with
                  cooperation with the requirements of the trial.

              16. Is pregnant or breastfeeding, or expecting to conceive or father children within
                  the projected duration of the study, starting with the screening visit through
                  120 days after the last dose of trial treatment.

              17. Is currently participating in or has participated in a study of an
                  investigational agent or has used an investigational device within 4 weeks prior
                  to the first dose of study treatment.
      
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:11 weeks
Safety Issue:
Description:Determine the pCR rate in patients with gastroesophageal adenocarcinoma (GEA) treated with neoadjuvant pembrolizumab followed by surgery. Regression of the primary tumor will be documented by the amount of viable tumor verses the amount of fibrosis using Becker Criteria.

Secondary Outcome Measures

Measure:Basic reproduction number (R0) resection rate
Time Frame:11 weeks
Safety Issue:
Description:GEA patients treated with neoadjuvant pembrolizumab using proximal, distal and circumferential margins to determine the completeness of resection. The absence of tumor cells at the proximal and distal margins will be required to be classified as an R0 resection.
Measure:Pathologic Response Grades (PRG)
Time Frame:11 weeks
Safety Issue:
Description:To determine rates of grade 1a (complete), 1b(minimal residual disease), 2 (partial response) and 3 (no response)
Measure:Number of patients with GEA taking pembrolizumab with treatment-related adverse events
Time Frame:11 weeks
Safety Issue:
Description:Evaluate the safety/tolerability patient response of pembrolizumab in patients with GEA. Number of patients with GEA taking pembrolizumab with treatment-related adverse events as assessed by CTCAE.
Measure:Disease Free Survival rate (DFS)
Time Frame:11 weeks
Safety Issue:
Description:to determine the DFS rate measured from the time of the first pembrolizumab dose and compare with patients who have surgery only
Measure:Overall Survival rate (OS)
Time Frame:11 weeks
Safety Issue:
Description:to determine the overall survival rate of patients measured from the time of first pembrolizumab dose compared to patients who have surgery only

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Chicago

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