- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00493025
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- Fertile patients must use effective contraception during and for 3 months after completion of study therapy 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Paclitaxel, Cisplatin, ZD1839 and Radiotherapy
Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
|
Cisplatin IV
Gefitinib IV
Other Names:
Paclitaxel IV
Other Names:
Postoperative ZD1839
Other Names:
Radiotherapy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathologic Complete Response Rate to the Neoadjuvant Regimen
Time Frame: 5 years
|
Study closed due to early stopping rule.
Patient data was not analyzed.
No additional information is available to report
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Survival
Time Frame: 5 years
|
5 years
|
Time to Progression
Time Frame: 5 years
|
5 years
|
Toxicity as Assessed by NCI CTC v2.0
Time Frame: 5 years
|
5 years
|
Safety and Tolerability of This Regimen
Time Frame: 5 years
|
5 years
|
Correlation Between EGFR Pathway Component Expression and Activation With Pathologic Complete Response and Survival
Time Frame: 5 years
|
5 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Arlene A. Forastiere, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Esophageal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Protein Kinase Inhibitors
- Paclitaxel
- Cisplatin
- Gefitinib
- Albumin-Bound Paclitaxel
Other Study ID Numbers
- J0386
- P30CA006973 (U.S. NIH Grant/Contract)
- JHOC-J0386
- 04-02-20-03 (Other Identifier: JHM IRB)
- ZENECA-IRUSIRES0304
- CDR0000549896 (Other Identifier: other)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Esophageal Cancer
-
OHSU Knight Cancer InstituteOregon Health and Science UniversityWithdrawnStage IIB Esophageal Cancer AJCC v7 | Stage III Esophageal Cancer AJCC v7 | Stage IIIA Esophageal Cancer AJCC v7 | Stage IIIB Esophageal Cancer AJCC v7 | Stage IIIC Esophageal Cancer AJCC v7
-
National Cancer Institute (NCI)NRG OncologyCompletedEsophageal Adenocarcinoma | Gastroesophageal Junction Adenocarcinoma | Stage IIA Esophageal Cancer AJCC v7 | Stage IIB Esophageal Cancer AJCC v7 | Stage IIIA Esophageal Cancer AJCC v7 | Stage IIIB Esophageal Cancer AJCC v7 | Stage IB Esophageal Cancer AJCC v7United States
-
AIO-Studien-gGmbHBristol-Myers SquibbCompletedEsophageal Cancer | Gastrooesophageal Cancer | Oesophageal Cancer | GastroEsophageal Cancer | Esophageal Cancers NOS | Oesophageal Cancer Metastatic | Esophageal Cancer Metastatic | Oesophageal Cancer NosGermany
-
Cancer Institute and Hospital, Chinese Academy...Tianjin Medical University Cancer Institute and Hospital; Sichuan Cancer Hospital...UnknownEsophageal Neoplasm | Esophageal Cancer TNM Staging Primary Tumor (T) T3 | Esophageal Cancer TNM Staging Primary Tumor (T) T2 | Esophageal Cancer TNM Staging Regional Lymph Nodes (N) N0 | Esophageal Cancer TNM Staging Distal Metastasis (M) M0China
-
University of Wisconsin, MadisonActive, not recruitingResectable Esophageal Cancer | GastroEsophageal CancerUnited States
-
Academisch Medisch Centrum - Universiteit van Amsterdam...UMC UtrechtCompletedEsophageal Cancer, Stage II | Esophageal Cancer Stage IIINetherlands
-
Tianjin Medical University Cancer Institute and...The First Affiliated Hospital with Nanjing Medical University; The First Affiliated... and other collaboratorsUnknownEsophageal Cancer Stage III | Esophageal Cancer Stage IIBChina
-
Tianjin Medical University Cancer Institute and...Sun Yat-sen University; Cancer Institute and Hospital, Chinese Academy of Medical... and other collaboratorsNot yet recruitingStage III Esophageal Cancer | Stage II Esophageal Cancer
-
Tianjin Medical University Cancer Institute and...UnknownStage III Esophageal Cancer | Stage II Esophageal CancerChina
-
National Cancer Institute (NCI)RecruitingNeoplasms | Esophageal Neoplasms | Esophagus Cancer | Esophagus Neoplasm | Neoplasms, Esophageal | Esophageal Cancer (EsC)United States
Clinical Trials on cisplatin
-
West China Second University HospitalRecruitingNeoadjuvant Chemotherapy | Epithelial Carcinoma, OvarianChina
-
Insmed IncorporatedCompletedOsteosarcoma MetastaticUnited States
-
Privo TechnologiesNational Cancer Institute (NCI)CompletedOral Squamous Cell CarcinomaUnited States
-
Samsung Medical CenterUnknownNasophayngeal Carcinoma Between Stage II and IVbKorea, Republic of
-
Cedars-Sinai Medical CenterRecruitingHPV Positive Oropharyngeal Squamous Cell CarcinomaUnited States
-
Korea Cancer Center HospitalCompletedCervical CancersKorea, Republic of
-
Taiho Oncology, Inc.Quintiles, Inc.Completed
-
Sun Yat-sen UniversityActive, not recruitingNasopharyngeal CarcinomaChina
-
Lawson Health Research InstituteRecruitingLocally Advanced Head and Neck Squamous Cell CarcinomaCanada
-
Sun Yat-sen UniversityFirst Affiliated Hospital, Sun Yat-Sen University; Guangdong Provincial People... and other collaboratorsActive, not recruitingNasopharyngeal Carcinoma | Nasopharyngeal Neoplasms | Nasopharyngeal Diseases | Head and Neck NeoplasmChina