Back to results

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

Primary Purpose

Esophageal Squamous Cell Carcinoma

Status

Recruiting

Phase

Phase 2

Locations

Israel

Study Type

Interventional

Intervention

Cisplatin

5-FU

Radiation therapy

Cetuximab

Nivolumab

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma focused on measuring Esophageal Cancer, Esophageal Squamous Cell Carcinoma, Cetuximab, Nivolumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

Rabin Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant Treatment

Arm Description

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

Outcomes

Primary Outcome Measures

pathological complete response (pCR) rate

pCR is defined when no tumor is found on pathology review of the surgical specimen (TRG -0)

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

Incidence of Treatment-Emergent Adverse Events (Safety)

Treatment-emergent AEs will be graded according to NCI CTCAE v5.0, vital signs and clinical laboratory

Secondary Outcome Measures

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

Full Information

NCT ID

NCT04229459

First Posted

January 13, 2020

Last Updated

January 13, 2020

Sponsor

Baruch Brenner

Collaborators

Bristol-Myers Squibb, Merck Serono International SA

1. Study Identification

Unique Protocol Identification Number

NCT04229459

Brief Title

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

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Recruiting

Study Start Date

December 30, 2019 (Actual)

Primary Completion Date

December 2022 (Anticipated)

Study Completion Date

June 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Baruch Brenner

Collaborators

Bristol-Myers Squibb, Merck Serono International SA

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Esophageal Squamous Cell Carcinoma

Keywords

Esophageal Cancer, Esophageal Squamous Cell Carcinoma, Cetuximab, Nivolumab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

31 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant Treatment

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

5-FU

Intervention Description

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

Radiation

Intervention Name(s)

Radiation therapy

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cetuximab

Other Intervention Name(s)

Erbitux

Intervention Description

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

Intervention Name(s)

Nivolumab

Other Intervention Name(s)

Opdivo

Intervention Description

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

Primary Outcome Measure Information:

Title

pathological complete response (pCR) rate

Description

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 36 months

Title

Progression Free Survival (PFS)

Description

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

Title

Incidence of Treatment-Emergent Adverse Events (Safety)

Description

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 36 months

Secondary Outcome Measure Information:

Title

Overall survival (OS)

Description

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 96 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Baruch Brenner, Prof

Phone

972-3-9378002

brennerb@clalit.org.il

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Baruch Brenner, Prof

Organizational Affiliation

Rabin Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Rabin Medical Center

City

Petach Tikva

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Baruch Brenner, Prof

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs