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

NCT04089904 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: IRB19-0310
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Gastroesophageal Junction Adenocarcinoma; Gastric Adenocarcinoma; Esophageal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR) Rate

  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.

  11 weeks

Secondary Outcomes (5)

• Basic Reproduction Number (R0) Resection Rate

  11 weeks

• Pathologic Response Grades (PRG)

  11 weeks

• Number of Patients With GEA Taking Pembrolizumab With Treatment-related Adverse Events

  11 weeks

• Disease Free Survival Rate (DFS)

  11 weeks

• Overall Survival Rate (OS)

  11 weeks

Study Arms (1)

ARM 1

EXPERIMENTAL

Drug: Pembrolizumab Injection

Interventions

Pembrolizumab Injection DRUG

Patients will receive 3 cycles of pembrolizumab at 200mg intravenously on day 1 of a 3 week cycle. After 3 cycles the patients will undergo surgery

ARM 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• 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.
• 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.
• HER2+ and HER2- patients, and all other known molecular subsets are eligible.
• Diagnostic laparoscopy is not mandated and can be performed as clinically indicated.
• Eligible for surgery with curative intent
• 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:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• 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.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Measurable or non-measurable disease by RECIST 1.1 will be allowed.
• 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.
• 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.
• 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

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• 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.
• 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).
• 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%.
• 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.
• 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.
• 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.
• 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.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• 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.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV).

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University Of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

pembrolizumab

Results Point of Contact

• Title: Theodore Karrison (Research Professor)
• Organization: University of Chicago

tkarrison@health.bsd.uchicago.edu

7737029326

Study Officials

• Daniel Catenacci, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2019
• First Posted: September 13, 2019
• Study Start: October 11, 2019
• Primary Completion: March 11, 2023
• Study Completion: March 11, 2023
• Last Updated: May 20, 2024
• Results First Posted: May 20, 2024

Record last verified: 2024-05

Locations

US (1)