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

This study is currently recruiting participants.
Verified March 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01196390
First received: September 4, 2010
Last updated: March 27, 2013
Last verified: March 2013
History of Changes
  Purpose

This randomized phase III trial is studying how well giving radiation therapy, paclitaxel, and carboplatin together with or without trastuzumab works 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 or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. 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
Adenocarcinoma of the Esophagus
Adenocarcinoma of the Gastroesophageal Junction
Stage IB Esophageal Cancer
Stage IIA Esophageal Cancer
Stage IIB Esophageal Cancer
Stage IIIA Esophageal Cancer
Stage IIIB Esophageal Cancer
 Radiation: radiation therapy
Drug: paclitaxel
Drug: carboplatin
Biological: trastuzumab
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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:

U.S. FDA Resources

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

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Adverse events [ Time Frame: From the start of chemoradiation up to the earlier date of surgery or 6 weeks after completion of chemoradiation ] [ Designated as safety issue: Yes ]
    Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  • Health-related quality of life (QOL) as measured by FACT-E [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.

  • Quality-adjusted survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The EQ-5D will be used to assess quality-adjusted survival. 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].

  • Molecular correlates of efficacy [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Predictors of cardiotoxicity [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 480
Study Start Date: July 2010
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (radiotherapy, chemotherapy, trastuzumab, surgery)
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 60 minutes on days 1, 8, 15, 22, 29, and 36 and trastuzumab IV over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57. Within 5-8 weeks after completion of radiotherapy, all patients undergo surgery. 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.
 Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Procedure: therapeutic conventional surgery
Undergo surgery
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
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 60 minutes on days 1, 8, 15, 22, 29, and 36. Within 5-8 weeks after completion of radiotherapy, all patients undergo surgery.
 Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Procedure: therapeutic conventional surgery
Undergo surgery
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically confirmed primary adenocarcinoma of the esophagus meeting the following criteria:

    • Involvement of mid (up to 25 cm), distal, or esophagogastric junction

      • Involvement of the stomach up to 5 cm allowed
      • Patients with tumors at the level of the carina or above must undergo bronchoscopy to exclude fistula

    • Stage T1, N1-2 or T2-3, N0-2 disease by chest, abdominal, or pelvic CT scan or whole-body PET/CT scan

      • No T1,N0 or T4 disease
      • No metastatic disease
    • Regional adenopathy including para-esophageal, gastric, gastrohepatic, and celiac (≤ 2 cm) nodes allowed
    • No cervical esophageal or proximal esophageal (15-24 cm) carcinoma
  • Intent to submit tissue for central HER2 testing
  • Must have undergone endoscopy with biopsy
  • HER2-overexpressing adenocarcinoma of the esophagus
  • Disease must be encompassed in 1 radiotherapy field
  • Able to undergo curative resection within 56 days after completion of chemoradiation
  • No evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi
  • Zubrod performance status 0-2
  • ANC ≥ 1,500 cells/mm³
  • Platelet count ≥100,000 cells/mm³
  • Hemoglobin (Hb) ≥ 8.0 g/dL (transfusion or other intervention to achieve Hb ≥ 8.0 g/dL allowed)
  • Creatinine ≤ 2 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • AST ≤ 3.0 times ULN
  • LVEF normal
  • Negative pregnancy test
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for ≥ 60 days after completion of chemotherapy or trastuzumab
  • No prior invasive malignancy except non-melanomatous skin cancer or curatively treated carcinoma in situ of the breast, oral cavity, or cervix with no evidence of disease within the past 2 years
  • No medical contraindications to esophagectomy
  • No prior allergic reaction to the study drugs involved in this protocol or to a monoclonal antibody
  • No history of congestive heart failure

  • No severe or active comorbidity defined as any of the following:

    • Unstable angina within the past 6 months
    • Transmural myocardial infarction within the past 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics

    • AIDS or immunocompromised patients

      • HIV testing is not required

  • No prior systemic chemotherapy for esophageal cancer

    • Prior chemotherapy for a different cancer allowed
  • No prior radiotherapy for esophageal cancer or prior chest radiotherapy
  • No prior anthracycline or taxane
  • No prior therapy with any agent targeting the HER2 pathway or HER1 (EGFR) pathway
  • No prior trastuzumab
  • No concurrent intensity-modulated radiotherapy
  • No other concurrent radiotherapy
  • No other concurrent investigational agents
  • No other concurrent cytotoxic agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01196390

  Show 195 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Howard Safran Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01196390     History of Changes
Other Study ID Numbers: NCI-2011-02601, RTOG 1010, CDR0000683717, U10CA021661
Study First Received: September 4, 2010
Last Updated: March 27, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Esophageal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Adenocarcinoma
Adenocarcinoma, Mucinous
Esophageal Diseases
Carcinoma
 Gastrointestinal Diseases
Digestive System Diseases
Trastuzumab
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 21, 2013