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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01196390
First received: September 4, 2010
Last updated: June 21, 2017
Last verified: June 2017
  Purpose
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.

Condition Intervention Phase
Esophageal Adenocarcinoma Gastroesophageal Junction Adenocarcinoma Stage IB Esophageal Cancer AJCC v7 Stage IIA Esophageal Cancer AJCC v7 Stage IIB Esophageal Cancer AJCC v7 Stage IIIA Esophageal Cancer AJCC v7 Stage IIIB Esophageal Cancer AJCC v7 Drug: Carboplatin Other: Laboratory Biomarker Analysis Drug: Paclitaxel Other: Quality-of-Life Assessment Radiation: Radiation Therapy Procedure: Therapeutic Conventional Surgery Biological: Trastuzumab Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2-Overexpressing Esophageal Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Disease-free survival (DFS) [ Time Frame: From the date of randomization to the date of first failure or last follow-up, assessed up to 8 years ]
    DFS will be estimated by the Kaplan-Meier method. The distribution of DFS estimates between the 2 arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, that may be associated with DFS.


Secondary Outcome Measures:
  • Health-related quality of life (QOL) as measured by FACT-E [ Time Frame: Up to 2 years ]
    Distributions of QOL data collection patterns over all collection points in each treatment arm will be described. To inspect the missing data mechanism for each tool, at least a graphical method will be used.

  • Incidence of adverse events, assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: From the start of chemoradiation up to the earlier date of surgery or 6 weeks after completion of chemoradiation ]
  • Molecular correlates of efficacy [ Time Frame: Up to 8 years ]
  • Overall survival (OS) [ Time Frame: From the date of randomization to the date of first failure or last follow-up, assessed up to 8 years ]
    OS will be estimated by the Kaplan-Meier method. The distribution of OS estimates between the 2 arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, that may be associated with OS.

  • Pathologic complete response [ Time Frame: Within 4 weeks after surgical resection ]
    Pathologic complete response is defined as no viable residual tumor cells.

  • Predictors of cardiotoxicity [ Time Frame: Up to 8 years ]
  • Quality-adjusted survival, assessed by the EQ-5D [ Time Frame: Up to 2 years ]
    Quality-adjusted survival is calculated as the weighted sum of different time in different health states added up to a total quality-adjusted survival time [U=sum of quality (qi) of health states K times the duration (si) spent in each health state].


Estimated Enrollment: 591
Actual Study Start Date: December 30, 2010
Estimated Primary Completion Date: August 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (radiotherapy, chemotherapy, trastuzumab)
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.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Procedure: Therapeutic Conventional Surgery
Undergo surgery
Biological: Trastuzumab
Given IV
Other Names:
  • ABP 980
  • Anti-c-ERB-2
  • Anti-c-erbB2 Monoclonal Antibody
  • Anti-ERB-2
  • Anti-erbB-2
  • Anti-erbB2 Monoclonal Antibody
  • Anti-HER2/c-erbB2 Monoclonal Antibody
  • Anti-p185-HER2
  • c-erb-2 Monoclonal Antibody
  • HER2 Monoclonal Antibody
  • Herceptin
  • Herceptin Biosimilar PF-05280014
  • Herceptin Trastuzumab Biosimilar PF-05280014
  • MoAb HER2
  • Monoclonal Antibody c-erb-2
  • Monoclonal Antibody HER2
  • PF-05280014
  • rhuMAb HER2
  • RO0452317
  • Trastuzumab Biosimilar ABP 980
  • Trastuzumab Biosimilar PF-05280014
Experimental: Arm II (radiotherapy and chemotherapy)
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.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Procedure: Therapeutic Conventional Surgery
Undergo surgery

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01196390

  Show 605 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Howard Safran NRG Oncology
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01196390     History of Changes
Other Study ID Numbers: NCI-2011-02601
NCI-2011-02601 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000683717
RTOG-1010
RTOG-1010 ( Other Identifier: NRG Oncology )
RTOG-1010 ( Other Identifier: CTEP )
U10CA180868 ( US NIH Grant/Contract Award Number )
U10CA021661 ( US NIH Grant/Contract Award Number )
Study First Received: September 4, 2010
Last Updated: June 21, 2017

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Trastuzumab
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 22, 2017