Esophageal Squamous Cell CarcinomaPhase 2NCT04229459
Trial of Nivolumab and Cetuximab After Chemoradiation in Esophageal Squamous Cell Carcinoma Patients.
A Phase 2 study testing Cisplatin, 5-FU and Radiation therapy in people with Esophageal Squamous Cell Carcinoma, run by Baruch Brenner at 1 site in Israel.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Squamous Cell Carcinoma
- What is being tested?
- Cisplatin, 5-FU and Radiation therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteIsrael
- Study dates
- 16 Feb 2020to 4 Apr 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Esophageal Squamous Cell Carcinoma
- Keywords
- Esophageal Cancer, Esophageal Squamous Cell Carcinoma, Cetuximab, Nivolumab
- Medical subject headings
- Esophageal Squamous Cell Carcinoma, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CisplatinDrug
Cisplatin 100mg/m2 IV on day 1 of induction chemotherapy, 75mg/m2 IV on day 1 and 29 of chemoradiation
5-FUDrug
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 therapyRadiation
1.8 Gy/fraction, 5 days a week for a total of 28 days
CetuximabDrug
Also called Erbitux
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
NivolumabDrug
Also called Opdivo
Nivolumab 3mg/kg IV on day 1 of each treatment cycle, every two weeks during immunotherapy
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant Treatment | Experimental | All subjects will receive induction chemotherapy and chemoradiation combined with cetuximab followed by nivolumab and cetuximab as neoadjuvant treatment Receives: Drug: Cisplatin; Drug: 5-FU; Radiation: Radiation therapy; Drug: Cetuximab; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathological complete response (pCR) rate
pCR is defined when no tumor is found on pathology review of the surgical specimen (TRG -0)
Measured: Time from start of neoadjuvant treatment until surgical resection, assessed up to 24 months
Modified pathological complete response
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.
Measured: 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.
Progression Free Survival (PFS)
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
Measured: 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
Incidence of Treatment-Emergent Adverse Events (Safety)
Treatment-emergent AEs will be graded according to NCI CTCAE v5.0, vital signs and clinical laboratory
Measured: Time from screening until the end of study drug administration, assessed up to 24 months
Secondary outcomes (1)
Overall survival (OS)
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
Measured: The time interval between the first day of treatment and the date of death from any cause, assessed up to 66 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2020
- Study start16 Feb 2020
- Primary completion12 Oct 2022
- Study completion4 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baruch Brenner
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Merck Serono International SA
- Responsible party
- Sponsor-investigator, Baruch Brenner, Rabin Medical Center
- Investigators
- Baruch Brenner, Prof, Principal investigator, Rabin Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04229459
- Sponsor's protocol ID
- CA209-76W / MS062202_0103
- Status last verified
- Jan 2026
- First submitted
- 13 Jan 2020
- Last updated
- 14 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the Addition of Nivolumab and Cetuximab to Chemoradiation in Locally Advanced Esophageal Squamous Cell Carcinoma (ESqCC).
- ClinicalTrials.gov ID
- NCT04229459
- Acronym / sponsor ID
- CA209-76W / MS062202_0103
- Conditions
- Esophageal Squamous Cell Carcinoma
- Keywords
- Esophageal Cancer, Esophageal Squamous Cell Carcinoma, Cetuximab, Nivolumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Baruch BrennerUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Merck Serono International SA
- Study start
- 16 Feb 2020 (actual)
- Primary completion
- 12 Oct 2022 (actual)
- Study completion
- 4 Apr 2027 (estimated)
- First posted
- 18 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant Treatment | Experimental | Drug: Cisplatin, Drug: 5-FU, Radiation: Radiation therapy, Drug: Cetuximab, Drug: NivolumabAll subjects will receive induction chemotherapy and chemoradiation combined with cetuximab followed by nivolumab and cetuximab as neoadjuvant treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CisplatinCisplatin 100mg/m2 IV on day 1 of induction chemotherapy, 75mg/m2 IV on day 1 and 29 of chemoradiation | Drug | Neoadjuvant Treatment |
| 5-FU5-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 | Drug | Neoadjuvant Treatment |
| Radiation therapy1.8 Gy/fraction, 5 days a week for a total of 28 days | Radiation | Neoadjuvant Treatment |
| CetuximabAlso: ErbituxCetuximab 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 | Drug | Neoadjuvant Treatment |
| NivolumabAlso: OpdivoNivolumab 3mg/kg IV on day 1 of each treatment cycle, every two weeks during immunotherapy | Drug | Neoadjuvant Treatment |
Primary outcome
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)
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.
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
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
1 secondary outcome
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2026.
Related trials for Esophageal Squamous Cell Carcinoma
RecruitingObservational study
Multicenter Prospective Cohort on Esophageal Endoscopic Submucosal Dissection
Superficial Esophageal Cancer, Oesophageal Adenocarcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
Recruiting
Individually Tailored, Supervised, Remote Exercise Intervention to Improve Physical Function for Stage I-III Gastroesophageal Cancer Survivors, PRECISE Trial
Clinical Stage I Esophageal Adenocarcinoma American Joint Committee on Cancer (AJCC) v8, Clinical Stage I Esophageal Squamous Cell Carcinoma AJCC v8
Not yet recruitingObservational study
Standardized Management of Esophageal Fistula in Esophageal Squamous Cell Carcinoma
Esophageal Squamous Cell Carcinoma (ESCC), Esophageal Fistula
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Baruch Brenner, Prof principal investigator
Rabin Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cisplatin, 5-FU and Radiation therapy in people with Esophageal Squamous Cell Carcinoma, run by Baruch Brenner at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathological complete response (pCR) rate (time frame: Time from start of neoadjuvant treatment until surgical resection, assessed up to 24 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2026.