Trial of Nivolumab and Cetuximab After Chemoradiation in Esophageal Squamous Cell Carcinoma Patients.
A Phase II Study of the Addition of Nivolumab and Cetuximab to Chemoradiation in Locally Advanced Esophageal Squamous Cell Carcinoma (ESqCC).
1 other identifier
interventional
12
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Feb 2020
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 13, 2020
CompletedFirst Posted
Study publicly available on registry
January 18, 2020
CompletedStudy Start
First participant enrolled
February 16, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 12, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
April 4, 2027
ExpectedJanuary 14, 2026
January 1, 2026
2.7 years
January 13, 2020
January 12, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
pathological complete response (pCR) rate
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
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.
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
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
Time from screening until the end of study drug administration, assessed up to 24 months
Secondary Outcomes (1)
Overall survival (OS)
The time interval between the first day of treatment and the date of death from any cause, assessed up to 66 months
Study Arms (1)
Neoadjuvant Treatment
EXPERIMENTALAll subjects will receive induction chemotherapy and chemoradiation combined with cetuximab followed by nivolumab and cetuximab as neoadjuvant treatment
Interventions
Cisplatin 100mg/m2 IV on day 1 of induction chemotherapy, 75mg/m2 IV on day 1 and 29 of chemoradiation
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
1.8 Gy/fraction, 5 days a week for a total of 28 days
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 3mg/kg IV on day 1 of each treatment cycle, every two weeks during immunotherapy
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Baruch Brennerlead
- Bristol-Myers Squibbcollaborator
- Merck Serono International SAcollaborator
Study Sites (1)
Rabin Medical Center
Petah Tikva, Israel
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Baruch Brenner, Prof
Rabin Medical Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Director of the Oncology Division and the Davidoff Cancer Center
Study Record Dates
First Submitted
January 13, 2020
First Posted
January 18, 2020
Study Start
February 16, 2020
Primary Completion
October 12, 2022
Study Completion (Estimated)
April 4, 2027
Last Updated
January 14, 2026
Record last verified: 2026-01