Trial of Nivolumab and Cetuximab After Chemoradiation in Esophageal Squamous Cell Carcinoma Patients.

January 12, 2026 updated by: Baruch Brenner

A Phase II Study of the Addition of Nivolumab and Cetuximab to Chemoradiation in Locally Advanced Esophageal Squamous Cell Carcinoma (ESqCC).

This is a phase II, open label, two-centered study for evaluation of the addition of nivolumab and cetuximab after chemoradiation as a neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma patients. Subjects must have received no prior treatment for esophageal cancer (chemotherapy, radiotherapy or surgery) and no prior treatment with checkpoint inhibitors.

Eligible subjects will receive induction chemotherapy with cetuximab for a period of 4 weeks, chemoradiation with cetuximab for a period of 6 weeks, 3 cycles of immunotherapy (nivolumab + cetuximab) for a period of 6 weeks, and will undergo surgery at the end of the treatment.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Petah Tikva, Israel
        • Rabin Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Signed written IRB approved informed consent.
  • Age > 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
  • Subjects with histologically confirmed operable, primary (non-recurrent) locally advanced (T3NxM0, TxN1M0) middle (distal to the thoracic inlet) or distal (up to the gastroesophageal junction) ESqCC according to endoscopic ultrasound (EUS) and PET-CT.
  • No prior systemic or radiation therapy for esophageal cancer.
  • Presence of adequate contraception in fertile patients.
  • Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
  • Women must not be breastfeeding.
  • No previous (within the last 5 years) or concurrent malignancies, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell carcinoma of the skin.

Exclusion Criteria:

  • Cervical esophageal tumors or tumors < 5 cm from the cricopharyngeal cartilage.
  • Gastric cancers with minor involvement of the GEJ or distal esophagus, or an esophageal tumor extending beyond 2 cm into the stomach.
  • Prior chest or upper abdomen radiotherapy, prior systemic chemotherapy within the past 5 years or prior esophageal or gastric surgery.
  • Patients with evidence of metastatic disease.
  • Biopsy proven tumor invasion of the tracheobronchial tree or presence of tracheo-esophageal (TE) fistula or recurrent laryngeal nerve or phrenic nerve paralysis.
  • New York Heart Association Class III or IV heart disease. Angina or myocardial infarction within the last 12 months, history of significant ventricular arrhythmia requiring medication with antiarrhythmics, or a history of a clinically significant conduction system abnormality.
  • Clinically significant hearing loss.
  • Patients with a history of seizure disorder who are receiving phenytoin, phenobarbital, or other antiepileptic medication.
  • Any positive test for hepatitis B virus or hepatitis C virus indicating active infection.
  • Ongoing immunosuppressive therapy.
  • Active autoimmune disease. [Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll].
  • Prior organ transplant.
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant Treatment
All subjects will receive induction chemotherapy and chemoradiation combined with cetuximab followed by nivolumab and cetuximab as neoadjuvant treatment
Drug: Cisplatin
Cisplatin 100mg/m2 IV on day 1 of induction chemotherapy, 75mg/m2 IV on day 1 and 29 of chemoradiation
Drug: 5-FU
5-FU 1000mg/m2/d IV on days 1-5 of induction chemotherapy, 1000mg/m2/d IV on days 1-4 and days 29-32 of chemoradiation
Radiation: Radiation therapy
1.8 Gy/fraction, 5 days a week for a total of 28 days
Drug: Cetuximab
Cetuximab 400mg/m2 IV on day 1 followed by 250mg/m2 IV weekly on induction chemotherapy, 250mg/m2 IV weekly on chemoradiation, 500mg/m2 IV on day 1 of each treatment cycle, every two weeks during immunotherapy
Other Names:
  • Erbitux
Drug: Nivolumab
Nivolumab 3mg/kg IV on day 1 of each treatment cycle, every two weeks during immunotherapy
Other Names:
  • Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: The time interval from the first day of treatment to the first event of loco-regional failure, metastatic recurrence or death from any cause, assessed up to 66 months
PFS will be censored in patients without loco-regional failure, metastatic recurrence or death, at the last date known to be alive or at the start of a new anti-cancer treatment, whatever occurs first. PFS rate will be estimated using the Kaplan-Meier method
The time interval from the first day of treatment to the first event of loco-regional failure, metastatic recurrence or death from any cause, assessed up to 66 months
pathological complete response (pCR) rate
Time Frame: Time from start of neoadjuvant treatment until surgical resection, assessed up to 24 months
pCR is defined when no tumor is found on pathology review of the surgical specimen (TRG -0)
Time from start of neoadjuvant treatment until surgical resection, assessed up to 24 months
Modified pathological complete response
Time Frame: Time from start of neoadjuvant treatment until surgical resection in operated patients (pCR) and long-term (≥12 months) clinical complete response (cCR) in unoperated patients, assessed up to 24 months.
We defined a novel primary endpoint, combining pathological complete response (pCR) rate among operated patients and long-term (≥12 months) clinical complete response (cCR) rate for those electing watchful waiting, into a composite endpoint of modified pCR (mpCR) rate.
Time from start of neoadjuvant treatment until surgical resection in operated patients (pCR) and long-term (≥12 months) clinical complete response (cCR) in unoperated patients, assessed up to 24 months.
Incidence of Treatment-Emergent Adverse Events (Safety)
Time Frame: Time from screening until the end of study drug administration, assessed up to 24 months
Treatment-emergent AEs will be graded according to NCI CTCAE v5.0, vital signs and clinical laboratory
Time from screening until the end of study drug administration, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: The time interval between the first day of treatment and the date of death from any cause, assessed up to 66 months
Patients who are still alive when last traced will be censored at the date of last follow-up. OS rate will be estimated using the Kaplan-Meier method
The time interval between the first day of treatment and the date of death from any cause, assessed up to 66 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Baruch Brenner

Collaborators

Bristol-Myers Squibb
Merck Serono International SA

Investigators

  • Principal Investigator: Baruch Brenner, Prof, Rabin Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 16, 2020

Primary Completion (Actual)

October 12, 2022

Study Completion (Estimated)

April 4, 2027

Study Registration Dates

First Submitted

January 13, 2020

First Submitted That Met QC Criteria

January 13, 2020

First Posted (Actual)

January 18, 2020

Study Record Updates

Last Update Posted (Estimated)

January 14, 2026

Last Update Submitted That Met QC Criteria

January 12, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA209-76W / MS062202_0103

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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