Clinical trial NCT04229459: Trial of Nivolumab and Cetuximab After Chemoradiation in Esophageal Squamous Cell Carcinoma Patients.
Official title: A Phase II Study of the Addition of Nivolumab and Cetuximab to Chemoradiation in Locally Advanced Esophageal Squamous Cell Carcinoma (ESqCC).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: Esophageal Cancer
Esophageal Squamous Cell Carcinoma
Cetuximab
Nivolumab
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: Merck Serono International SA
First posted: 2020-01-18
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: pathological complete response (pCR) rate
timeFrame: Time from start of neoadjuvant treatment until surgical resection, assessed up to 36 months
measure: Progression Free Survival (PFS)
timeFrame: 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
measure: Incidence of Treatment-Emergent Adverse Events (Safety)
timeFrame: Time from screening until the end of study drug administration, assessed up to 36 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: The time interval between the first day of treatment and the date of death from any cause, assessed up to 96 months
Other outcomes:
Locations:
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
Study officials:
affiliation: Rabin Medical Center
name: Baruch Brenner, Prof
role: PRINCIPAL_INVESTIGATOR
References: