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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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Esophageal Cancer

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Trial Information

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


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.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically confirmed, newly diagnosed locally advanced
adenocarcinoma or squamous cell carcinoma of the esophagus Evidence of disease extension
into or through the wall of the esophagus (T2- T4) and/or regional nodal metastases (N1)
Patients with distant metastatic disease or who cannot undergo resection may also be
treated on the phase I portion of this trial but are not eligible for the modified phase
II portion Patients entered in the modified phase II portion of the trial must have
evaluable (measurable in one dimension) or measurable disease at the primary site

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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose

Outcome Description:

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.

Outcome Time Frame:

8 weeks

Safety Issue:

Yes

Principal Investigator

Stephen A. Bernard, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

LCCC 9622

NCT ID:

NCT00002984

Start Date:

March 1997

Completion Date:

January 2007

Related Keywords:

  • Esophageal Cancer
  • stage II esophageal cancer
  • stage III esophageal cancer
  • stage IV esophageal cancer
  • squamous cell carcinoma of the esophagus
  • adenocarcinoma of the esophagus
  • Adenocarcinoma
  • Esophageal Diseases
  • Esophageal Neoplasms

Name

Location

Lineberger Comprehensive Cancer Center, UNCChapel Hill, North Carolina  27599-7295