Study of Pembrolizumab in Locally Advanced Esophageal Adenocarcinoma

NCT02998268 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 1602016966
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 4

Brief Summary

This is a randomized, multicenter phase II study of pembrolizumab in combination with chemotherapy and chemoradiation in locally advanced esophageal adenocarcinoma to examine the safety and efficacy of the combination of pembrolizumab with chemotherapy and chemoradiation in locally advanced esophageal adenocarcinoma as assessed by 1 year disease free survival rate.

Conditions

Esophageal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Major Pathological Response

  Tumor tissue will be assessed for major pathological response as defined as complete response or near complete response. Pathologic response was assessed by tumor regression grade. This is a pathologic assessment of the amount of residual cancer cells in the specimen and the degree of fibrosis in the sample specimen. A completer response is 0% residual cancer cells. A partial response is 10-50% residual cancer cells, and no response is \>50% residual cancer cells within the tumor specimen.

  Between approximately week 15 to 19

Secondary Outcomes (3)

• R0 Resection Rate.

  1 year

• Overall Survival Rates

  Until death from any cause or for a maximum of 5 years

• Number of Participants That Remained Progression Free as of 1 Year

  1 year

Other Outcomes (5)

• Reduction of Local Immune Infiltration.

  Up to 1 year post-surgery

• Prediction of Tumor Response.

  Up to 1 year post-surgery

• Improved 1 Year Survival

  1 year

Study Arms (2)

Cohort 1

OTHER

Subjects in Cohort 1 receive conventional induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion.

Drug: Pembrolizumab; Drug: Taxol; Drug: Carboplatin

Cohort 2

EXPERIMENTAL

Subjects in Cohort 2 receive pembrolizumab along with induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion.

Drug: Pembrolizumab; Drug: Taxol; Drug: Carboplatin

Interventions

Pembrolizumab DRUG

Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

Also known as: Keytruda

Cohort 1; Cohort 2

Taxol DRUG

Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions.

Also known as: Paclitaxel

Cohort 1; Cohort 2

Carboplatin DRUG

Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed esophageal or GEJ adenocarcinoma
• Clinical tumor stage should be T2 Npositive M0 or T3--T4, Nany, M0
• Be willing and able to provide written informed consent/assent for the trial
• Be 18 years of age or older on day of signing informed consent.
• Be a candidate for surgical resection.
• Be willing to provide tissue during endoscopic assessment of their tumor.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined below, all screening labs should be performed within 14 days of treatment initiation.
• Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets≥100,000 / mcL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion within 7 days of assessment
• Serum creatinine OR Measured or calculated creatinine clearance ≤1.5 X upper limit of normal (ULN) OR
• ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (Creatinine clearance should be calculated per institutional standard) (GFR can also be used in place of creatinine or CrCl)
• Serum total bilirubin ≤ 1.5 X ULN OR
• Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Evidence of metastatic disease.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has active TB or a history of active TB within 10 years of registration (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer treatment, including chemotherapy, radiation, or monoclonal antibody (mAb) for their current diagnosis of esophageal adenocarcinoma.
• Has a known additional malignancy that is active. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has a previous invasive malignancy treated with curative intent less than 3 years from time of registration. Exceptions include prostate cancer, basal cell squamous skin cancer, and cervical cancer.
• 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 known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

USC Keck School of Medicine, Norris Cancer Center

Los Angeles, California, 90033, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-5848, United States

Location

Weill Cornell Medicine

New York, New York, 10068, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

pembrolizumab; Paclitaxel; Carboplatin

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Dr. Manish Shah
• Organization: Weill Cornell Medicine

mas9313@med.cornell.edu

646-962-6200

Study Officials

• Manish Shah, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 20, 2016
• Study Start: March 7, 2017
• Primary Completion: February 10, 2021
• Study Completion: March 1, 2026
• Last Updated: March 17, 2026
• Results First Posted: May 2, 2024

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)