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

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

A Phase II Study of the Addition of Nivolumab and Cetuximab to Chemoradiation in Locally Advanced Esophageal Squamous Cell Carcinoma (ESqCC).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04229459
• Other study ID #: CA209-76W / MS062202_0103
• Status: Recruiting
• Phase: Phase 2
• Start date: December 30, 2019
• Est. completion date: June 2027

Study information

• Verified date: January 2020
• Source: Rabin Medical Center
• Contact: Baruch Brenner, Prof
• Phone: 972-3-9378002
• Email: brennerb[@]clalit.org.il
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 31
• Est. completion date: June 2027
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

Intervention

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

Radiation:
• Radiation therapy
1.8 Gy/fraction, 5 days a week for a total of 28 days

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

Locations

Country	Name	City	State
Israel	Rabin Medical Center	Petach Tikva

Sponsors (3)

Lead Sponsor	Collaborator
Baruch Brenner	Bristol-Myers Squibb, Merck Serono International SA

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 36 months
Primary	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
Primary	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 36 months
Secondary	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	The time interval between the first day of treatment and the date of death from any cause, assessed up to 96 months