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

NCT ID: NCT00493025

Last Updated: 2018-12-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30
• Study Completion Date: 2013-03-31

Brief Summary

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.

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.

Conditions

Esophageal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Paclitaxel, Cisplatin, ZD1839 and Radiotherapy

Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

Cisplatin IV

gefitinib

Intervention Type: DRUG

Gefitinib IV

paclitaxel

Intervention Type: DRUG

Paclitaxel IV

adjuvant therapy

Intervention Type: PROCEDURE

Postoperative ZD1839

radiation therapy

Intervention Type: RADIATION

Radiotherapy

Interventions

cisplatin

Cisplatin IV

Intervention Type: DRUG

gefitinib

Gefitinib IV

Intervention Type: DRUG

paclitaxel

Paclitaxel IV

Intervention Type: DRUG

adjuvant therapy

Postoperative ZD1839

Intervention Type: PROCEDURE

radiation therapy

Radiotherapy

Intervention Type: RADIATION

Other Intervention Names

Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839; Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839; Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839; Combined Modality Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839

Eligibility Criteria

Inclusion Criteria

• 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
• 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

Exclusion Criteria

• Known severe hypersensitivity to gefitinib or any of its excipients
• Evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
• Evidence of other significant clinical disorder or laboratory finding that would preclude study participation
• Evidence of clinically active interstitial lung disease
• Chronic, stable radiographic changes that are asymptomatic are eligible
• 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
• Preexisting peripheral neuropathy > grade 1
• Incomplete healing from prior oncologic or other major surgery
• Prior chemotherapy, radiotherapy, or surgery for this cancer
• More than 30 days since prior nonapproved or investigational drugs
• Concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, or Hypericum perforatum (St. John's wort)
• Concurrent oral retinoids

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arlene A. Forastiere, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Related Links

http://cancer.gov/clinicaltrials

Clinical trial summary from the National Cancer Institute's PDQ® database

Other Identifiers

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J0386

Identifier Type: -

Identifier Source: secondary_id

04-02-20-03

Identifier Type: OTHER

Identifier Source: secondary_id

ZENECA-IRUSIRES0304

Identifier Type: -

Identifier Source: secondary_id

CDR0000549896

Identifier Type: OTHER

Identifier Source: secondary_id

J0386

Identifier Type: -

Identifier Source: org_study_id