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

NCT ID: NCT04229459

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-16
• Study Completion Date: 2027-04-04

Brief 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. 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant Treatment

All subjects will receive induction chemotherapy and chemoradiation combined with cetuximab followed by nivolumab and cetuximab as neoadjuvant treatment

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

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

Nivolumab

Intervention Type: DRUG

Nivolumab 3mg/kg IV on day 1 of each treatment cycle, every two weeks during immunotherapy

Cisplatin

Intervention Type: DRUG

Cisplatin 100mg/m2 IV on day 1 of induction chemotherapy, 75mg/m2 IV on day 1 and 29 of chemoradiation

5-FU

Intervention Type: DRUG

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 therapy

Intervention Type: RADIATION

1.8 Gy/fraction, 5 days a week for a total of 28 days

Interventions

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

Intervention Type: DRUG

Nivolumab

Nivolumab 3mg/kg IV on day 1 of each treatment cycle, every two weeks during immunotherapy

Intervention Type: DRUG

Cisplatin

Cisplatin 100mg/m2 IV on day 1 of induction chemotherapy, 75mg/m2 IV on day 1 and 29 of chemoradiation

Intervention Type: 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

Intervention Type: DRUG

Radiation therapy

1.8 Gy/fraction, 5 days a week for a total of 28 days

Intervention Type: RADIATION

Other Intervention Names

Erbitux; Opdivo

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Merck Serono International SA

INDUSTRY

Sponsor Role: collaborator

Baruch Brenner

OTHER

Sponsor Role: lead

Responsible Party

Baruch Brenner

Director of the Oncology Division and the Davidoff Cancer Center

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Baruch Brenner, Prof

Role: PRINCIPAL_INVESTIGATOR

Rabin Medical Center

Locations

Rabin Medical Center

Petah Tikva, , Israel

Countries

Israel

Other Identifiers

CA209-76W / MS062202_0103

Identifier Type: -

Identifier Source: org_study_id