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Paclitaxel, Cisplatin, Gefitinib, and Radiation Therapy Followed by Surgery and Gefitinib in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction That Can Be Removed By Surgery

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ClinicalTrials.gov Identifier: NCT00493025
Recruitment Status : Terminated (Completed as planned)
First Posted : June 27, 2007
Last Update Posted : August 16, 2011
Sponsor:
Collaborator:
Information provided by:

June 25, 2007
June 27, 2007
August 16, 2011
April 2005
July 2011   (Final data collection date for primary outcome measure)
Pathologic complete response rate to the neoadjuvant regimen [ Time Frame: 5 years ]
Pathologic complete response rate to the neoadjuvant regimen
Complete list of historical versions of study NCT00493025 on ClinicalTrials.gov Archive Site
  • Toxicity as assessed by NCI CTC v2.0 [ Time Frame: 5 years ]
  • Safety [ Time Frame: 5 years ]
  • Time to progression [ Time Frame: 5 years ]
  • Survival [ Time Frame: 5 years ]
  • Correlation between EGFR pathway component expression and activation with pathologic complete response and survival [ Time Frame: 5 years ]
  • Toxicity as assessed by NCI CTC v2.0
  • Safety
  • Time to progression
  • Survival
  • Correlation between EGFR pathway component expression and activation with pathologic complete response and survival
Not Provided
Not Provided
 
Paclitaxel, Cisplatin, Gefitinib, and Radiation Therapy Followed by Surgery and Gefitinib in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction That Can Be Removed By Surgery
Phase II Study in Operable Adenocarcinoma of the Esophagus to Measure Response Rate and Toxicity of Preoperative Combined Modality Paclitaxel (Taxol®, Bristol-Myers Squibb), Cisplatin (Platinol®, Abbott Laboratories), ZD1839 (IRESSA®) and Radiotherapy Followed by Postoperative ZD1839

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving gefitinib after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving paclitaxel, cisplatin, gefitinib, and radiation therapy followed by surgery and gefitinib works in treating patients with locally advanced cancer of the esophagus or gastroesophageal junction that can be removed by surgery.

OBJECTIVES:

Primary

  • Determine the pathologic complete response rate in patients with resectable, locally advanced adenocarcinoma of the esophagus or gastroesophageal junction treated with neoadjuvant paclitaxel, cisplatin, gefitinib, and radiotherapy followed by surgery and adjuvant gefitinib.

Secondary

  • Determine the survival of patients treated with this regimen.
  • Determine the safety and tolerability of this regimen in these patients.
  • Determine time to disease progression in patients treated with this regimen.
  • Determine the plasma pharmacokinetics of unbound gefitinib in these patients.
  • Conduct exploratory studies to determine if EGFR pathway component expression and activation correlates with response to therapy and survival of these patients.
  • Determine if treatment with gefitinib alters the EGFR pathway in these patients.

OUTLINE: This is a prospective study.

  • Neoadjuvant therapy: Patients receive oral gefitinib beginning 14 days prior to the start of chemoradiotherapy and continuing until 7 days prior to surgery (10-12 weeks). Patients also receive paclitaxel IV over 1 hour and cisplatin IV over 2-3 hours on days 1, 8, 15, 22, and 29. Patients also undergo radiotherapy 5 days a week for 5 weeks.
  • Surgery: Patients undergo surgical resection 4-6 weeks after the completion of neoadjuvant therapy.
  • Adjuvant therapy: Patients receive gefitinib once a day beginning 2-8 weeks after surgery and continuing for up to 1 year in the absence of disease progression or unacceptable toxicity.

Blood samples are obtained at baseline and periodically during study for pharmacokinetic studies. Tumor tissue samples are obtained by core biopsy at baseline for biomarker correlative studies. Samples are analyzed by IHC to measure expression and activation of EGFR-signaling pathway biomarkers in pretreatment esophageal tumor tissue, including EGFR and phosphorylated (p)-EGFR, ERK and p-ERK, Akt and p-Akt, p70s6k and p-p70s6k, and p27.

After completion of study therapy, patients are followed periodically for at least 5 years.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Esophageal Cancer
  • Drug: cisplatin
    Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
    Other Name: Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
  • Drug: gefitinib
    Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
    Other Name: Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
  • Drug: paclitaxel
    Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
    Other Name: Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
  • Genetic: gene expression analysis
    Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
    Other Name: Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
  • Other: immunohistochemistry staining method
    Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
    Other Name: Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
  • Other: laboratory biomarker analysis
    Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
    Other Name: Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
  • Other: pharmacological study
    Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
    Other Name: Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
  • Procedure: adjuvant therapy
    Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
    Other Name: Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
  • Procedure: biopsy
    Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
    Other Name: Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
  • Procedure: conventional surgery
    Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
    Other Name: Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
  • Procedure: neoadjuvant therapy
    Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
    Other Name: Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
  • Radiation: radiation therapy
    Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
    Other Name: Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
36
July 2011
July 2011   (Final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction meeting the following criteria:

    • Newly diagnosed disease
    • Surgically resectable tumor
    • Primary esophageal tumor < 20 cm below the incisors
    • Tumor extending ≤ 2 cm into the cardia
  • Stage T2-3, N0-1, M0-1a tumor, as determined by imaging studies and biopsy

    • Documentation by endoscopic ultrasound, endoscopy, and CT scan of the chest and abdomen required
    • Any lesion suspicious for metastasis must be biopsied
    • M1a disease (i.e., celiac nodal metastasis) is allowed if other eligibility criteria are met
    • T4 disease (i.e., involvement of the pleura, pericardium, or diaphragm) allowed provided it is considered resectable
  • No CNS metastasis

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Granulocyte count > 1,000/mm³
  • Platelet count > 75,000/mm³
  • Creatinine clearance > 60 mL/min
  • Total bilirubin < 1.5 mg/dL
  • No concurrent illness likely to preclude protocol therapy or surgical resection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study therapy
  • No known severe hypersensitivity to gefitinib or any of its excipients
  • No evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
  • No evidence of other significant clinical disorder or laboratory finding that would preclude study participation
  • No evidence of clinically active interstitial lung disease

    • Patients with chronic, stable radiographic changes that are asymptomatic are eligible
  • No other prior or concurrent malignancy except basal cell or squamous cell skin cancer, cervical cancer, or any other curatively treated malignancy from which the patient has been disease-free and has a survival prognosis of > 5 years
  • No preexisting peripheral neuropathy > grade 1

PRIOR CONCURRENT THERAPY:

  • No incomplete healing from prior oncologic or other major surgery
  • No prior chemotherapy, radiotherapy, or surgery for this cancer

    • Endoscopy with biopsy and dilation is allowed
  • More than 30 days since prior nonapproved or investigational drugs
  • No concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, or Hypericum perforatum (St. John's wort)
  • No concurrent oral retinoids
Sexes Eligible for Study: All
18 Years to 80 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00493025
JHOC-J0386, CDR0000549896
P30CA006973 ( U.S. NIH Grant/Contract )
JHOC-J0386
JHOC-04-02-20-03
ZENECA-IRUSIRES0304
Not Provided
Not Provided
Not Provided
Arlene A. Forastiere, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Arlene A. Forastiere, MD Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP