Clinical Trials /

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

NCT01196390

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Carcinoma
  • Gastric Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Radiation</span> Therapy, <span class="go-doc-concept go-doc-intervention">Paclitaxel,</span> and <span class="go-doc-concept go-doc-intervention">Carboplatin</span> With or Without <span class="go-doc-concept go-doc-intervention">Trastuzumab</span> in Treating Patients With Esophageal <span class="go-doc-concept go-doc-disease">Cancer</span>

Title

  • Brief Title: Radiation Therapy, Paclitaxel, and Carboplatin With or Without Trastuzumab in Treating Patients With Esophageal Cancer
  • Official Title: A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of Her2-Overexpressing Esophageal Adenocarcinoma
  • Clinical Trial IDs

    NCT ID: NCT01196390

    ORG ID: NCI-2011-02601

    NCI ID: NCI-2011-02601

    Trial Conditions

    Adenocarcinoma of the Gastroesophageal Junction

    Esophageal Adenocarcinoma

    Stage IB Esophageal Cancer

    Stage IIA Esophageal Cancer

    Stage IIB Esophageal Cancer

    Stage IIIA Esophageal Cancer

    Stage IIIB Esophageal Cancer

    Trial Interventions

    Drug Synonyms Arms
    Carboplatin Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplat, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo Arm I (radiotherapy, chemotherapy, trastuzumab), Arm II (radiotherapy and chemotherapy)
    Paclitaxel Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat Arm I (radiotherapy, chemotherapy, trastuzumab), Arm II (radiotherapy and chemotherapy)

    Trial 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 block tumor growth by targeting
    certain tumor cells and causing them to die. 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.

    TERTIARY 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 paclitaxel intravenously (IV) over 60 minutes and carboplatin IV over 30-60 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. 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.

    Trial Arms

    Name Type Description Interventions
    Arm I (radiotherapy, chemotherapy, trastuzumab) Experimental 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 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. Carboplatin, Paclitaxel
    Arm II (radiotherapy and chemotherapy) Experimental 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. Carboplatin, Paclitaxel

    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

    - Platelets >=100,000 cells/mm

    - 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Disease-free survival (DFS)

    Secondary Outcome Measures

    Adverse events

    Health-related quality of life (QOL) as measured by FACT-E

    Molecular correlates of efficacy

    Overall survival (OS)

    Pathologic complete response

    Predictors of cardiotoxicity

    Quality-adjusted survival

    Trial Keywords