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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
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
Rabin Medical Center
Petah Tikva, Israel
pathological complete response (pCR) rate
pCR is defined when no tumor is found on pathology review of the surgical specimen (TRG -0)
Time frame: 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 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.
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
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
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 frame: Time from screening until the end of study drug administration, assessed up to 24 months
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
Time frame: The time interval between the first day of treatment and the date of death from any cause, assessed up to 66 months
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