Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Advanced or Metastatic Cancer of the Esophagus
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|ClinicalTrials.gov Identifier: NCT00002984|
Recruitment Status : Completed
First Posted : July 30, 2004
Last Update Posted : May 24, 2012
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.
|Condition or disease||Intervention/treatment||Phase|
|Esophageal Cancer||Drug: cisplatin Drug: fluorouracil Drug: paclitaxel Procedure: surgical procedure Radiation: radiation therapy||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Paclitaxel Combined With 5-FU and Cisplatin Concomitant With Radiotherapy in the Management of Locally Advanced or Metastatic Esophageal Cancer (Adenocarcinoma and Squamous Histologies) - A Phase I/Modified Phase II Trial|
|Study Start Date :||March 1997|
|Actual Primary Completion Date :||May 2006|
|Actual Study Completion Date :||January 2007|
- Drug: 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
- 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 coursesOther Name: 5-FU
- Drug: paclitaxel
30 mg/m2 - 45 mg/m2 given weekly. The dose each subject receives will depend on when they enter the study
- Procedure: surgical procedure
Surgical resection should take place approximately 4 weeks following completion of the chemotherapy.
- Radiation: 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
- Maximum Tolerated Dose [ Time Frame: 8 weeks ]Define the maximum tolerated dose of paclitaxel when given as a 3-hour infusion in combination with cisplatin, 5-FU, and radiation therapy. The MTD will be defined as the dose level immediately below that which caused dose limiting toxicity (DLT) in a third or more of the patients in any cohort.
- Number of subjects experiencing adverse events [ Time Frame: 8 weeks ]Adverse drug events will be graded using the Common Toxicity Criteria for Adverse Events (CTCAE), graded 1-5 with 5 being death.
- Efficacy of treatment [ Time Frame: 2 years ]Evaluate the effectiveness of a paclitaxel-containing chemotherapy regimen and concomitant 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, distant failure rate, and overall survival as determined by radiographic evlauation
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002984
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center, UNC|
|Chapel Hill, North Carolina, United States, 27599-7295|
|Study Chair:||Stephen A. Bernard, MD||UNC Lineberger Comprehensive Cancer Center|