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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

Primary Purpose

Esophageal Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

cisplatin

gefitinib

paclitaxel

adjuvant therapy

radiation therapy

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring adenocarcinoma of the esophagus, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Paclitaxel, Cisplatin, ZD1839 and Radiotherapy

Arm Description

Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839

Outcomes

Primary Outcome Measures

Pathologic Complete Response Rate to the Neoadjuvant Regimen

Study closed due to early stopping rule. Patient data was not analyzed. No additional information is available to report

Secondary Outcome Measures

Toxicity as Assessed by NCI CTC v2.0

Safety and Tolerability of This Regimen

Time to Progression

Survival

Correlation Between EGFR Pathway Component Expression and Activation With Pathologic Complete Response and Survival

Full Information

NCT ID

NCT00493025

First Posted

June 25, 2007

Last Updated

November 12, 2018

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00493025

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Terminated

Why Stopped

Closed due to early stopping rule-Low accrual

Study Start Date

April 2005 (undefined)

Primary Completion Date

March 2013 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Esophageal Cancer

Keywords

adenocarcinoma of the esophagus, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

19 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Paclitaxel, Cisplatin, ZD1839 and Radiotherapy

Arm Type

Experimental

Arm Description

Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839

Intervention Type

Drug

Intervention Name(s)

cisplatin

Intervention Description

Cisplatin IV

Intervention Type

Drug

Intervention Name(s)

gefitinib

Other Intervention Name(s)

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

Intervention Description

Gefitinib IV

Intervention Type

Drug

Intervention Name(s)

paclitaxel

Other Intervention Name(s)

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

Intervention Description

Paclitaxel IV

Intervention Type

Procedure

Intervention Name(s)

adjuvant therapy

Other Intervention Name(s)

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

Intervention Description

Postoperative ZD1839

Intervention Type

Radiation

Intervention Name(s)

radiation therapy

Other Intervention Name(s)

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

Intervention Description

Radiotherapy

Primary Outcome Measure Information:

Title

Pathologic Complete Response Rate to the Neoadjuvant Regimen

Description

Study closed due to early stopping rule. Patient data was not analyzed. No additional information is available to report

Time Frame

5 years

Secondary Outcome Measure Information:

Title

Toxicity as Assessed by NCI CTC v2.0

Time Frame

5 years

Title

Safety and Tolerability of This Regimen

Time Frame

5 years

Title

Time to Progression

Time Frame

5 years

Title

Survival

Time Frame

5 years

Title

Correlation Between EGFR Pathway Component Expression and Activation With Pathologic Complete Response and Survival

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Arlene A. Forastiere, MD

Organizational Affiliation

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21231-2410

Country

United States

12. IPD Sharing Statement

Links:

URL

http://cancer.gov/clinicaltrials

Description

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

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