NCT03604991|SuspendedPhase 2FDA Drug

Study Stopped

End of Initial Phase of Multi-phase protocol

Nivolumab and Ipilimumab in Treating Patients With Esophageal and Gastroesophageal Junction Adenocarcinoma Undergoing Surgery

A Phase II/III Study of Peri-Operative Nivolumab and Ipilimumab in Patients With Locoregional Esophageal and Gastroesophageal Junction Adenocarcinoma

National Cancer Institute (NCI)ClinicalTrials.gov

Compare

3 other identifiers

NCI-2018-01575EA2174U10CA180820

Study Type

interventional

Target

278

Locations

1 country

Sites

489

Timeline

RegisteredJul 2018

StartedMay 2019

CompletionDec 2026

Brief Summary

This phase II/III trial studies the usefulness of treatment with nivolumab and ipilimumab in addition to standard of care chemotherapy and radiation therapy in patients with esophageal and gastroesophageal junction adenocarcinoma who are undergoing surgery. Immunotherapy with antibodies, such as nivolumab and ipilimumab, may remove the brake on the body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy and radiation therapy may reduce the tumor size and the amount of normal tissue that needs to be removed during surgery. A combined treatment with nivolumab and ipilimumab, chemotherapy, and radiation therapy might be more effective in patients with esophageal and gastroesophageal junction adenocarcinoma who are undergoing surgery.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial recruitment is currently suspended

Enrollment

278

participants targeted

Target at P75+ for phase_2

Timeline

6mo left

Started May 2019

Longer than P75 for phase_2

Geographic Reach

1 country

489 active sites

Status

suspended

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7.7 years study duration

Study Progress93%

May 2019Dec 2026

First Submitted

Initial submission to the registry

July 27, 2018

Completed

3 days until next milestone

First Posted

Study publicly available on registry

July 30, 2018

Completed

9 months until next milestone

Study Start

First participant enrolled

May 3, 2019

Completed

7.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Last Updated

May 29, 2026

Status Verified

April 1, 2026

Enrollment Period

7.7 years

First QC Date

July 27, 2018

Last Update Submit

May 28, 2026

Conditions

Clinical Stage III Esophageal Adenocarcinoma AJCC v8 Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8 Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8 Esophageal Adenocarcinoma Clinical Stage II Esophageal Adenocarcinoma AJCC v8 Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8 Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

Pathologic complete response (Step I)
The study with compare the pathologic complete response of Arm A and Arm B using a one-sided 0.10 level chi-squared test for proportions.
Up to 5 weeks
Disease-free survival (DFS) (Step 2)
DFS measured from the adjuvant treatment randomization will be the endpoint of the adjuvant portion of the study and to achieve the desired power it is expected that patients will be followed for an additional year post completion of accrual to the adjuvant portion. The DFS comparison will be between patients randomized to Arm C (nivolumab) versus Arm D (nivolumab plus ipilimumab) using a one-sided 0.10 level stratified log rank test.
From the adjuvant treatment randomization assessed for up to 7 years

Secondary Outcomes (3)

Incidence of adverse events
Up to 7 years
Overall survival
From the time of first randomization up to 7 years
DFS
From the time of first randomization up to 7 years

Other Outcomes (1)

Percent change in mean volumetric apparent diffusion coefficient (ADC)
Baseline to mid-treatment

Study Arms (4)

Arm A (carboplatin, paclitaxel, radiation therapy)

EXPERIMENTAL

Patients receive carboplatin IV and paclitaxel IV once weekly and undergo radiation therapy QD (Monday-Friday) beginning on day 1 of each cycle. Cycles repeat every week for up to 5 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or PET scan during screening and follow-up and undergo collection of blood samples throughout the trial.

Procedure: Biospecimen CollectionDrug: CarboplatinProcedure: Computed TomographyDrug: PaclitaxelProcedure: Positron Emission TomographyRadiation: Radiation Therapy

Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)

EXPERIMENTAL

Patients receive carboplatin, paclitaxel, and radiation therapy as in Arm A. Patients also receive nivolumab IV over 30 minutes on days 1 and 15 of each cycle. Cycles repeat every week for up to 5 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or PET scan during screening and follow-up and undergo collection of blood samples throughout the trial.

Procedure: Biospecimen CollectionDrug: CarboplatinProcedure: Computed TomographyBiological: NivolumabDrug: PaclitaxelProcedure: Positron Emission TomographyRadiation: Radiation Therapy

Arm C (nivolumab)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and collection of blood samples throughout the trial.

Procedure: Biospecimen CollectionProcedure: Computed TomographyBiological: Nivolumab

Arm D (nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive nivolumab as in Arm C and receive ipilimumab IV over 90 minutes on day 1 of cycles 1 and 4 and day 15 of cycles 2 and 5. Treatment repeats every 4 weeks for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and collection of blood samples throughout the trial.

Procedure: Biospecimen CollectionProcedure: Computed TomographyBiological: IpilimumabBiological: Nivolumab

Interventions

NivolumabBIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)Arm C (nivolumab)Arm D (nivolumab, ipilimumab)

CarboplatinDRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm A (carboplatin, paclitaxel, radiation therapy)Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)

Biospecimen CollectionPROCEDURE

Undergo collection of blood sample

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm A (carboplatin, paclitaxel, radiation therapy)Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)Arm C (nivolumab)Arm D (nivolumab, ipilimumab)

PaclitaxelDRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm A (carboplatin, paclitaxel, radiation therapy)Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)

Radiation TherapyRADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm A (carboplatin, paclitaxel, radiation therapy)Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)

IpilimumabBIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016, Ipilimumab Biosimilar CS1002, MDX 010, MDX-010, MDX-CTLA4, MDX010, Yervoy

Arm D (nivolumab, ipilimumab)

Positron Emission TomographyPROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Arm A (carboplatin, paclitaxel, radiation therapy)Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)

Computed TomographyPROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm A (carboplatin, paclitaxel, radiation therapy)Arm B (carboplatin, paclitaxel, radiation therapy, nivolumab)Arm C (nivolumab)Arm D (nivolumab, ipilimumab)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

STEP 1 RANDOMIZATION: Patients must be age \>= 18 years
STEP 1 RANDOMIZATION: Patients must have histologically confirmed T1N1-3M0 or T2-3N0-2M0 esophageal or gastroesophageal junctional adenocarcinoma (Siewert I and II)
STEP 1 RANDOMIZATION: Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
STEP 1 RANDOMIZATION: Patents must be deemed a surgical candidate by a thoracic surgeon, surgical oncologist, or surgeon who is qualified to perform an esophagectomy
STEP 1 RANDOMIZATION: Absolute neutrophil count \>= 1,500/mcL (within less than or equal to 14 days prior to randomization)
STEP 1 RANDOMIZATION: Platelets \>= 100,000/mcL (within less than or equal to 14 days prior to randomization)
STEP 1 RANDOMIZATION: Total bilirubin =\< institutional upper limit of normal (ULN) (within less than or equal to 14 days prior to randomization)
STEP 1 RANDOMIZATION: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (within less than or equal to 14 days prior to randomization)
STEP 1 RANDOMIZATION: Serum creatinine =\< 1.5 x institutional ULN (within less than or equal to 14 days prior to randomization)
STEP 1 RANDOMIZATION: Hemoglobin (Hgb) \>= 9 g/dL (within less than or equal to 14 days prior to randomization)
STEP 1 RANDOMIZATION: Leukocytes \>= 3,000/mm\^3 (within less than or equal to 14 days prior to randomization)
STEP 1 RANDOMIZATION: Patients may not have received prior chemotherapy or radiation therapy for management for this malignancy
STEP 1 RANDOMIZATION: Patients may not have received prior immunotherapy for management of this malignancy or for any other past malignancy
STEP 1 RANDOMIZATION: Patients must have no contraindication to receiving either carboplatin or paclitaxel chemotherapy
STEP 1 RANDOMIZATION: Patients must have no contraindication to receiving radiation therapy
+32 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (489)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Alaska Breast Care and Surgery LLC