Pembrolizumab With Locally Delivered Radiation Therapy for the Treatment of Metastatic Esophageal Cancers

NCT02642809 | Completed Phase 1 Results DMC FDA Drug FDA Device

• 1 other identifier: 201603087
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose to treat patients with metastatic esophageal cancers and dysphagia with two fractions of brachytherapy followed by pembrolizumab. The brachytherapy is hypofractionated and will provide a radiation dose of sufficient intensity to induce the release of tumor-derived antigens and trigger an antitumor immune response. The simplicity of the design should maximize the chance to examine the hypothesis that radiotherapy can induce an immune response, which can then be augmented by pembrolizumab treatment. Success in this study would provide the impetus to conduct further trials aimed at developing this unique strategy as a more broadly applicable therapeutic option in the treatment of patients suffering from these deadly cancers, and will provide important mechanistic insights into the relationship between radiation treatment and immune therapy augmentation.

Conditions

Esophageal Cancer; Cancer of the Esophagus

Outcome Measures

Primary Outcomes (1)

• Safety as Measured by Number of Participants With Grade 3 or Higher Treatment Related Adverse Events

  The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 will be utilized for all toxicity reporting. In general, CTCAE version 4.03 has the following definitions for the grading scale: Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

  Through 30 days after completion of treatment (median length of adverse event follow-up 106 days, full range 42-1023 days)

Secondary Outcomes (6)

• Mean Percent Change in Esophageal Tumor Length as Measured by Endoscopy

  Prior to brachytherapy and once anytime between 2-6 months after start of pembrolizumab (up to approximately 7 months post-baseline)

• Change in Esophageal Lumen Size as Measured by Endoscopy

  Prior to brachytherapy, at 1-2 weeks after initiation of brachytherapy (optional), and 2-6 months after start of pembrolizumab

• Worst Grade of Dysphagia Experienced by Participant

  From start of treatment through 8 weeks post-pembrolizumab (median length of dysphagia follow-up 132 days, full range 42-1049 days)

• Overall Response as Measured by Immune-Related Response Criteria (irRC)

  Through completion of treatment (median length of treatment 76 days, full range 25-993 days)

• Median Progression-free Survival (PFS)

  Up to 1 year after completion of treatment (median length of treatment 76 days, full range 25-993 days)

Study Arms (1)

Pembrolizumab and Brachytherapy

EXPERIMENTAL

* Brachytherapy dose=16 Gy delivered in 2 fractions of 8 Gy per fraction, separated by 7-10 days between fractions. * Pembrolizumab started within 1 week after completion of brachytherapy administered as an intravenous infusion with a dose of 200 mg. It will be given every 3 weeks. * Research endoscopic biopsy for 8 consented patients will take place 1-2 weeks after initiation of brachytherapy.

Drug: Pembrolizumab; Radiation: Brachytherapy

Interventions

Pembrolizumab DRUG

Provided by Merck.

Also known as: MK-3475, Keytruda

Pembrolizumab and Brachytherapy

Brachytherapy RADIATION

It will be delivered using a high-dose-rate Ir-192 afterloader via a dedicated esophageal applicator.

Pembrolizumab and Brachytherapy

Eligibility Criteria

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

You may qualify if:

• Any patient with metastatic esophageal cancer that is deemed a candidate for brachytherapy for local control or treatment of dysphagia as determined by treating physician
• Presence of an evaluable metastatic lesion (locoregional lymph nodes are acceptable)
• At least 18 years of age.
• ECOG performance status 0-2
• Adequate bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 x IULN OR Direct bilirubin ≤ IULN for patients with total bilirubin \> 1.5 x IULN
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (or ≤ 5 x IULN for patients with liver metastases)
• Serum creatinine ≤ 1.5 x IULN OR Creatinine clearance by Cockcroft-Gault ≥ 60 mL/min/1.73 m2 for patients with creatinine levels \> 1.5 x IULN
• INR or PT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
• aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of a anticoagulants
• Sexually active women of childbearing potential and men must agree to use contraceptive methods prior to study entry, for the duration of study participation, and for 120 days after the last dose of pembrolizumab. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Either enrolled in HRPO# 201107221 ("Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information for Patients with Gastrointestinal Cancers"), which facilitates the collection of specimens for correlative studies, or consenting to collection of blood and tissue as part of this protocol for research testing.

You may not qualify if:

• Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Received a live vaccine within 30 days prior to the first dose of pembrolizumab. 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 (e.g. 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 pembrolizumab.
• Currently receiving any other investigational agents, has participated in a study of an investigational agent, or use of an investigational device within 4 weeks of the first dose of pembrolizumab.
• Has received systemic therapy within 4 weeks of the first dose of pembrolizumab.
• Known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of MK-3475 and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or other agents used in the study.
• Uncontrolled intercurrent illness that would limit compliance with study requirements. This would include, but is not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, immunosuppression, autoimmune conditions, underlying pulmonary disease, or psychiatric illness/social situations.
• Has an active autoimmune disease requiring systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• History of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 72 hours of study entry.
• Known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as HCV RNA \[qualitative\] is detected).
• Known history of active TB.
• Known history of HIV (HIV 1/2 antibodies).

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

pembrolizumab; Brachytherapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics

Results Point of Contact

• Title: Dr. Cliff Robinson
• Organization: Washington University School of Medicine

clifford.robinson@wustl.edu

314-362-8567

Study Officials

• Cliff Robinson, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2015
• First Posted: December 30, 2015
• Study Start: June 8, 2016
• Primary Completion: September 24, 2020
• Study Completion: August 3, 2021
• Last Updated: March 18, 2026
• Results First Posted: March 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)