NCT01196390 · CITED IN SOURCE DOCUMENTS

Radiation Therapy, Paclitaxel, and Carboplatin With or Without Trastuzumab in Treating Patients With Esophageal Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-06-02

This randomized phase III trial studies how well radiation therapy, paclitaxel, and carboplatin with or without trastuzumab work in treating patients with esophageal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving radiation therapy and combination chemotherapy together with or without trastuzumab is more effective in treating esophageal cancer.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Disease-free Survival (DFS)

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outcome · POSTED

Percentage of Participants With Pathologic Complete Response at Surgery

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outcome · POSTED

Overall Survival

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outcome · POSTED

Frequency of Highest Grade Adverse Event Per Participant

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outcome · POSTED

Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment

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outcome · POSTED

Quality-adjusted Survival

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outcome · POSTED

Molecular Correlates of Efficacy

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outcome · POSTED

Number of Participants With Any Cardiac Adverse Events Regardless of Attribution

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outcome · POSTED

Disease-free Survival (DFS) by Sex

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outcome · POSTED

Disease-free Survival (DFS) by Ethnicity

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outcome · POSTED

Disease-free Survival (DFS) by Race

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Pathologically confirmed primary adenocarcinoma of the esophagus that involves the mid (up to 25 cm), distal, or esophagogastric junction; the cancer may involve the stomach up to 5 cm * Endoscopy with biopsy * PRIOR TO STEP 1 REGISTRATION BUT WITHIN 56 DAYS PRIOR TO STEP 2 REGISTRATION * Intent to submit tissue for central HER2 testing * Stage T1N1-2, T2-3N0-2, according to the American Joint Committee on Cancer (AJCC) 7th edition staging, based on the following minimum diagnostic work-up: * Chest/abdominal/pelvic computed tomography (CT) or whole-body positron emission tomography (PET)/CT (NOTE: if CT is performed at this time point, whole-body PET/CT will be required prior to step 2 registration; PET/CT of skull base to mid-thigh is acceptable) (NOTE: if adenopathy is noted on CT or whole-body PET/CT scan, an endoscopic ultrasound is not required prior to STEP 2 registration as long as adequate tissue has been obtained for central HER2 testing) * Patients may have regional adenopathy including para-esophageal, gastric, gastrohepatic and celiac nodes; if celiac adenopathy is present, it must be =\< 2 cm * Patients with tumors at the level of the carina or above must undergo bronchoscopy to exclude fistula * Zubrod performance status 0-2 * Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 * Platelets \>= 100,000 cells/mm\^3 * Hemoglobin \>= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 8.0 g/dL is acceptable) * Creatinine =\< 2 times upper limit of normal * Bilirubin =\< 1.5 times upper limit of normal * Aspartate aminotransferase (AST) =\< 3.0 times upper limit of normal * For women of childbearing potential, a negative serum or urine pregnancy test * Patients must sign a study-specific informed consent prior to study entry * CONDITIONS FOR PATIENT ELIGIBILITY PRIOR TO STEP 2 REGISTRATION (HER2-POSITIVE PATIENTS ONLY) * HER2 expressing adenocarcinoma of the esophagus centrally * Surgical consultation to confirm that patient will be able to undergo curative resection after completion of chemoradiation within 56 days prior to step 2 registration * Radiation oncology consultation to confirm that disease can be encompassed in a radiotherapy field within 56 days prior to step 2 registration * Consultation with a medical oncologist within 56 days prior to step 2 registration * Stage T1N1-2, T2-3N0-2, according to the AJCC 7th edition staging, based upon the following minimum diagnostic work-up: * History/physical examination, with documentation of the patient's weight, within 14 days prior to step 2 registration * Whole-body PET/CT scan within 56 days prior to step 2 registration (if only CT performed prior to step 1 registration) * Endoscopic ultrasound within 56 days prior to step 2 registration, unless the patient is found to have adenopathy per CT or whole-body PET/CT scan * Electrocardiogram (EKG) within 56 days prior to step 2 registration * Serum creatinine =\< 2 x the upper limit or normal within 14 days prior to step 2 registration * Zubrod performance status 0-2 within 14 days prior to step 2 registration * For women of childbearing potential, a negative serum pregnancy test within 14 days prior to step 2 registration * Left ventricular ejection fraction (LVEF) \>= institutional lower limit of normal by cardiac echocardiogram (echo) or multi gated acquisition (MUGA) scan within 56 days prior to step 2 registration * Women of childbearing potential and sexually active male participants must agree to practice adequate contraception while on study and for at least 60 days following the last dose of chemotherapy or trastuzumab Exclusion Criteria: * Patients with cervical esophageal carcinoma * Patients with T1N0 disease, T4 disease, and proximal esophageal cancers (15-24 cm) * Prior systemic chemotherapy for esophageal cancer; note that prior chemotherapy for a different cancer is allowable * Prior radiation therapy for esophageal cancer or prior chest radiotherapy * Prior anthracycline or taxane * Evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi * Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 2 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are permissible) * Medical contraindications to esophagectomy * Prior therapy with any agent targeting the HER2 pathway or human epidermal growth factor receptor 1 (HER1) (epidermal growth factor receptor \[EGFR\]) pathway * Prior therapy with trastuzumab * Prior allergic reaction to the study drugs involved in this protocol or to a monoclonal antibody * Previous history of congestive heart failure * Severe, active comorbidity, defined as follows: * Unstable angina in the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immunocompromised patients * Pregnant or nursing women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57 and paclitaxel intravenously IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Beginning 21-56 days after surgery, patients receive trastuzumab IV over 30-90 minutes. Treatment repeats every 21 days for 13 courses in the absence of disease progression or unacceptable toxicity.
intervention Names
Drug: Carboplatin
Other: Laboratory Biomarker Analysis
Drug: Paclitaxel
Other: Quality-of-Life Assessment
Radiation: Radiation Therapy
Procedure: Therapeutic Conventional Surgery
Biological: Trastuzumab
label
Arm I (radiotherapy, chemotherapy, trastuzumab)
type
EXPERIMENTAL
description
Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36.
intervention Names
Drug: Carboplatin
Other: Laboratory Biomarker Analysis
Drug: Paclitaxel
Other: Quality-of-Life Assessment
Radiation: Radiation Therapy
Procedure: Therapeutic Conventional Surgery
label
Arm II (radiotherapy and chemotherapy)
type
EXPERIMENTAL

interventions

arm Group Labels
Arm I (radiotherapy, chemotherapy, trastuzumab)
Arm II (radiotherapy and chemotherapy)
description
Given IV
name
Carboplatin
other Names
Blastocarb
Carboplat
Carboplatin Hexal
Carboplatino
Carboplatinum
Carbosin
Carbosol
Carbotec
CBDCA
Displata
Ercar
JM-8
type
DRUG
arm Group Labels
Arm I (radiotherapy, chemotherapy, trastuzumab)
Arm II (radiotherapy and chemotherapy)
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER
arm Group Labels
Arm I (radiotherapy, chemotherapy, trastuzumab)
Arm II (radiotherapy and chemotherapy)
description
Given IV
name
Paclitaxel
other Names
Anzatax
Asotax
Bristaxol
Praxel
Taxol
Taxol Konzentrat
type
DRUG
arm Group Labels
Arm I (radiotherapy, chemotherapy, trastuzumab)
Arm II (radiotherapy and chemotherapy)
description
Ancillary studies
name
Quality-of-Life Assessment
other Names
Quality of Life Assessment
type
OTHER
arm Group Labels
Arm I (radiotherapy, chemotherapy, trastuzumab)
Arm II (radiotherapy and chemotherapy)
description
Undergo radiation therapy
name
Radiation Therapy
other Names
Cancer Radiotherapy
Energy Type
ENERGY_TYPE
Irradiate
Irradiated
Irradiation
Radiation
Radiation Therapy, NOS
Radiotherapeutics
Radiotherapy
RT
Therapy, Radiation
type
RADIATION
arm Group Labels
Arm I (radiotherapy, chemotherapy, trastuzumab)
Arm II (radiotherapy and chemotherapy)
description
Undergo surgery
name
Therapeutic Conventional Surgery
type
PROCEDURE
arm Group Labels
Arm I (radiotherapy, chemotherapy, trastuzumab)
description
Given IV
name
Trastuzumab
other Names
ABP 980
ALT02
CT-P06
CT-P6
Herceptin
Herceptin Biosimilar PF-05280014
Herceptin Trastuzumab Biosimilar PF-05280014
Herzuma
Kanjinti
Ogivri
Ontruzant
PF-05280014
type
BIOLOGICAL

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 203
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
NIH-required analysis. A disease event is defined as local/regional persistence or recurrence of the cancer under study, distant metastases, a new second primary cancer, or death due to any cause. Participants undergoing surgery who had an R2 resection and participants not undergoing surgery who had a positive endoscopic biopsy or no biopsy at all were considered to have local persistence of disease. Disease-free survival time is defined as time from randomization to the date of first disease event or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 162 events were reported.
measure
Disease-free Survival (DFS) by Sex
time Frame
From randomization to last follow-up. Maximum follow-up at time of analysis was 8.0 years.
description
NIH-required analysis. A disease event is defined as local/regional persistence or recurrence of the cancer under study, distant metastases, a new second primary cancer, or death due to any cause. Participants undergoing surgery who had an R2 resection and participants not undergoing surgery who had a positive endoscopic biopsy or no biopsy at all were considered to have local persistence of disease. Disease-free survival time is defined as time from randomization to the date of first disease event or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 162 events were reported.
measure
Disease-free Survival (DFS) by Ethnicity
time Frame
From randomization to last follow-up. Maximum follow-up at time of analysis was 8.0 years.
description
NIH-required analysis. A disease event is defined as local/regional persistence or recurrence of the cancer under study, distant metastases, a new second primary cancer, or death due to any cause. Participants undergoing surgery who had an R2 resection and participants not undergoing surgery who had a positive endoscopic biopsy or no biopsy at all were considered to have local persistence of disease. Disease-free survival time is defined as time from randomization to the date of first disease event or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 162 events were reported.
measure
Disease-free Survival (DFS) by Race
time Frame
From randomization to last follow-up. Maximum follow-up at time of analysis was 8.0 years.

primary Outcomes

description
A disease event is defined as local/regional persistence or recurrence of the cancer under study, distant metastases, a new second primary cancer, or death due to any cause. Participants undergoing surgery who had an R2 resection and participants not undergoing surgery who had a positive endoscopic biopsy or no biopsy at all were considered to have local persistence of disease. Disease-free survival time is defined as time from randomization to the date of first disease event or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 162 events were reported.
measure
Disease-free Survival (DFS)
time Frame
From randomization to last follow-up. Maximum follow-up at time of analysis was 8.0 years.

secondary Outcomes

description
Pathologic Complete Response (pCR) is evaluated after surgery and is based on the pathology review of the submitted surgical specimen. Pathologic Complete Response occurs if the pathologist determines that the resected esophageal specimen, accompanying lymph nodes, and surgical margins are all free of tumor.
measure
Percentage of Participants With Pathologic Complete Response at Surgery
time Frame
At the time of surgery, 5-8 weeks after completion of radiation therapy.
description
Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis occurred after 109 deaths were reported.
measure
Overall Survival
time Frame
From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.
description
Common Terminology Criteria for Adverse Events (version 4.0 before 4-1-2018; then version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data provided is in this outcome measure; see Adverse Events Module for specific adverse event data.
measure
Frequency of Highest Grade Adverse Event Per Participant
time Frame
From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.
description
The ECS is a 17-item self-report instrument designed to measure multidimensional quality of life in patients with esophagus cancer with a total score ranging from 0-68. It is to be administered with the Functional Assessment of Cancer Therapy - General (FACT-G). A higher score indicates better QOL. Improvement is defined as an increase from the baseline score of at least 5 points.
measure
Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment
time Frame
Baseline, 6-8 weeks after end of radiation therapy (approximately 11.5-13.5 weeks from treatment start), 1 and 2 years from treatment start
measure
Quality-adjusted Survival
time Frame
From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years.
measure
Molecular Correlates of Efficacy
time Frame
From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years.
description
Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event (AE) severity from 1=mild to 5=death. Logistic regression was used to evaluate treatment arm, clinical tumor stage (T stage), Zubrod Performance Status, gender, presence of adenopathy, and age as possible predictors of cardiac adverse events. Results of the final model are reported in the statistical analysis section. Summary adverse event data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
measure
Number of Participants With Any Cardiac Adverse Events Regardless of Attribution
time Frame
From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.

Full study description

brief Summary: This randomized phase III trial studies how well radiation therapy, paclitaxel, and carboplatin with or without trastuzumab work in treating patients with esophageal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving radiation therapy and combination chemotherapy together with or without trastuzumab is more effective in treating esophageal cancer.
detailed Description: PRIMARY OBJECTIVES: l. To determine if trastuzumab increases disease-free survival when combined with trimodality treatment (radiation plus chemotherapy followed by surgery) for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing esophageal adenocarcinoma. SECONDARY OBJECTIVES: I. To evaluate if the addition of trastuzumab to trimodality treatment increases the pathologic complete response rate and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma. II. To develop a tissue bank of tumor tissue from patients with non-metastatic esophageal adenocarcinoma. III. To determine molecular correlates of complete pathologic response, disease-free survival, and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma treated with neoadjuvant and maintenance trastuzumab. IV. To evaluate predictors of cardiotoxicity in patients with esophageal cancer treated with trastuzumab and chemoradiation. V. To evaluate adverse events associated with the addition of trastuzumab to trimodality treatment for patients with non-metastatic esophageal adenocarcinoma. PATIENT-REPORTED QUALITY OF LIFE OBJECTIVES: I. To determine if the addition of trastuzumab to trimodality treatment improves the patient-reported Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E) Esophageal Cancer Subscale (ECS) score. II. To determine if an improvement in the FACT-E ECS score at 6-8 weeks post completion of neoadjuvant chemoradiation correlates with pathologic complete response. III. To determine if pathologic complete response correlates with the FACT-E ECS score at 1 year and/or 2 years from the start of chemoradiation. IV. To determine if the addition of trastuzumab to trimodality treatment improves the Swallow Index and Eating Index Subscale scores of the FACT-E. V. To determine if the addition of trastuzumab to paclitaxel, carboplatin, and radiation impacts quality-adjusted survival. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive trastuzumab intravenously (IV) over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57 and paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Beginning 21-56 days after surgery, patients receive trastuzumab IV over 30-90 minutes. Treatment repeats every 21 days for 13 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Within 5-8 weeks after completion of radiotherapy, all patients undergo surgery. After completion of study therapy, patients are followed up every 4 months for 2 years and then yearly thereafter.

Source references

references

citation
Safran HP, Winter K, Ilson DH, Wigle D, DiPetrillo T, Haddock MG, Hong TS, Leichman LP, Rajdev L, Resnick M, Kachnic LA, Seaward S, Mamon H, Diaz Pardo DA, Anderson CM, Shen X, Sharma AK, Katz AW, Salo J, Leonard KL, Moughan J, Crane CH. Trastuzumab with trimodality treatment for oesophageal adenocarcinoma with HER2 overexpression (NRG Oncology/RTOG 1010): a multicentre, randomised, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):259-269. doi: 10.1016/S1470-2045(21)00718-X. Epub 2022 Jan 14.
pmid
35038433
type
DERIVED