Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Advanced or Metastatic Cancer of the Esophagus

NCT ID: NCT00002984

Last Updated: 2012-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-03-31
• Study Completion Date: 2007-01-31

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than on drug and combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy plus radiation therapy in treating patients with advanced or metastatic cancer of the esophagus.

Detailed Description

OBJECTIVES: I. Define the maximum tolerated dose (MTD) of paclitaxel (TAX) when given as a 3 hour infusion in combination with cisplatin (CDDP), fluorouracil (5-FU), and radiation therapy. II. Define the toxicity profile of TAX when given as a 3 hour infusion in combination with CDDP, 5-FU, and radiation therapy. III. Evaluate the effectiveness of a TAX containing chemotherapy regimen and concurrent radiotherapy followed by resection in the treatment of locally advanced esophageal cancer as judged by the complete response rate, pathological complete response rate, time to recurrence, and overall survival.

OUTLINE: Patients receive radiation to the tumor and nodal area 5 days a week for 5 weeks. Patients receive chemotherapy consisting of cisplatin (CDDP) via rapid intravenous infusion on day 1 followed by fluorouracil (5-FU) via 96-hour continuous infusion (CI) on days 1 through 4; this is repeated on the last 4 days of radiation therapy (days 29-31), with an additional dose of CDDP on day 29 and a 96-hour CI of 5-FU on days 29-31. Patients also receive paclitaxel (TAX) as a weekly 3 hour infusion on days 1, 8, 15, and 29, with 3 patients treated at each dose level and subsequent patients treated according to the toxicity observed in previous cohorts. TAX will be given prior to the CDDP and 5-FU on the weeks when it is given concurrently. The MTD of TAX is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity. Surgical resection takes place 2-8 weeks following completion of chemoradiotherapy in all patients except those with disease progression and those who are surgically unresectable or medically unfit (includes those with metastatic disease) to tolerate surgery. An additional course of TAX/CDDP/5-FU is given 28-35 days after surgery.

PROJECTED ACCRUAL: Three patients will be entered into the lowest dose level of TAX, and 3-6 patients entered into up to three additional dose levels of TAX for the phase I study. An additional group of up to 11 patients will be accrued for the first stage of the modified phase II study and 38 to the second stage, if warranted. The study will be completed within 3-4 years.

Conditions

Esophageal Cancer

Study Design

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

Interventions

cisplatin

Cisplatin will be given at a dose of 100 mg/m2 at a concentration of 1 mg/ml over one hour on Day 1 and 29 for a total of 2 courses

Intervention Type: DRUG

fluorouracil

5-FU will be given at 500 mg/m2 in 1 liter D5 1/2 by continuous infusion every 12 hours for a total of 8 doses (Total 1.0 g/m2/day X 4 days) on Days 1-4 and 29-32 for a total of 2 courses

Intervention Type: DRUG

paclitaxel

30 mg/m2 - 45 mg/m2 given weekly. The dose each subject receives will depend on when they enter the study

Intervention Type: DRUG

surgical procedure

Surgical resection should take place approximately 4 weeks following completion of the chemotherapy.

Intervention Type: PROCEDURE

radiation therapy

The dose of radiation to the tumor and nodal area will be 4500 cGy given as 180 cGy fractions daily, Monday through Friday, for 5 weeks

Intervention Type: RADIATION

Other Intervention Names

5-FU

Eligibility Criteria

Inclusion Criteria

PATIENT CHARACTERISTICS: Age: 18 or over Performance status: ECOG 0-2 Life expectancy: Greater than 2 months for those with metastatic disease or 2 years for those with locally advanced disease Hematopoietic: WBC at least 4,000/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9.0 g/dL Hepatic: Bilirubin no greater than 2.0 mg/dl Renal: Creatinine clearance at least 60 mL/min Serum creatinine no greater than 1.5 mg/dL Cardiovascular: No history of refractory congestive heart failure or cardiomyopathy Other: Not pregnant No other malignancy within 5 years except: Curatively treated carcinoma in situ of the cervix Basal cell carcinoma of the skin

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy Surgery: More than 1 week since major surgery

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen A. Bernard, MD

Role: STUDY_CHAIR

UNC Lineberger Comprehensive Cancer Center

Locations

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Countries

United States

Other Identifiers

CDR0000065519

Identifier Type: -

Identifier Source: secondary_id

NCI-G97-1240

Identifier Type: -

Identifier Source: secondary_id

LCCC 9622

Identifier Type: -

Identifier Source: org_study_id