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

This study has been terminated.
(Completed as planned)
Sponsor:
Collaborator:
Information provided by:
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00493025
First received: June 25, 2007
Last updated: August 15, 2011
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Esophageal Cancer
Drug: cisplatin
Drug: gefitinib
Drug: paclitaxel
Genetic: gene expression analysis
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: adjuvant therapy
Procedure: biopsy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Pathologic complete response rate to the neoadjuvant regimen [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity as assessed by NCI CTC v2.0 [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Safety [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Time to progression [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Correlation between EGFR pathway component expression and activation with pathologic complete response and survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: April 2005
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    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
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00493025

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Arlene A. Forastiere, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Arlene A. Forastiere, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00493025     History of Changes
Other Study ID Numbers: JHOC-J0386, CDR0000549896, P30CA006973, JHOC-J0386, JHOC-04-02-20-03, ZENECA-IRUSIRES0304
Study First Received: June 25, 2007
Last Updated: August 15, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
adenocarcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Adenocarcinoma
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Paclitaxel
Gefitinib
Cisplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Radiation-Sensitizing Agents
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014