Perioperative Vs. Preoperative Chemotherapy With Surgery in the Squamous Carcinoma of Esophagus

October 20, 2010 updated by: Health Science Center of Xi'an Jiaotong University

Perioperative Versus Preoperative Chemotherapy With Surgery in Patients With Locoregional Squamous Carcinoma of Esophagus

To assess whether or not a perioperative therapy with surgery can improve the outcomes among patients with potentially curable squamous carcinoma of esophagus as compared to a preoperative chemotherapy followed by surgery

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Perioperative chemotherapy has been shown to significantly improve the R0 resection rate, the disease free survival and the overall survival in patients with adenocarcinoma of the esophagus, the gastroesophageal junction and the stomach. Therefore, perioperative chemotherapy is the new therapeutic standard (Cunningham NEJM 2006, MRC, Lancet 2002, Boige ASCO 2007). The best-evaluated regime is the combination of Epirubicin, Cisplatin and 5-FU (ECF) (Cunningham, NEJM 2007). Cisplatin and 5-FU are considered to be the most important components to form the cornerstone of this regime.

Paclitaxel is a new and highly active cytotoxic agent. In a randomized phase II study, the dual combination of Paclitaxel and 5-FU seemed to show similar effects as ECF, administered as first line treatment. The triplet combination of Paclitaxel, Cisplatin and 5-FU has significantly superior efficacy than a combination of Cisplatin und 5-FU (Van Cutsem, JCO 2007).

It has been shown that Capecitabine is more active than 5-FU and can replace intravenous 5-FU in the combination with Cisplatin in the treatment of esophageal cancer. Capecitabine therefore is FDA approved for esophageal cancer (Cunningham, ASCO 2006, Kang ASCO 2006).It seems reasonable to optimize perioperative chemotherapy by including this modern chemotherapeutics.

In this study, patients with squamous carcinoma of esophagus and gastroesophageal junction who seem operable with curative intent according to oncological and surgical assessment are treated with 2 preoperative cycles of PCF followed by surgical resection, followed by 2 postoperative cycles of PCF. Among patients with no responses to preoperative chemotherapy, Capecitabine 625 mg/m² twice-daily dose is defined as alternatives to infused 5-Fluorouracil in the postoperative chemotherapy regimen Postoperative chemotherapy will start within 4-6 weeks after the operation. 3 weeks after the end of the last chemotherapy the final investigation (end of study visit) will be done.

Study Type

Interventional

Enrollment (Actual)

350

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shaanxi
      • Xi'an, Shaanxi, China, 710061
        • First Affiliated Hospital of College of Medicine of Xi'an Jiao Tong University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Signed informed consent
  • histologically confirmed esophageal cancer (squamous carcinoma) measurable, non-metastatic disease
  • no previous cancer therapy (chemotherapy, radiotherapy or resection)
  • life expectancy > 3 months
  • age > 18 years
  • WHO Status ≤ 1
  • Intended curative resection according to evaluation of an experienced surgeon
  • Negative pregnancy blood test at screening but not earlier than 72 hours prior to start of chemotherapy for women with child bearing potential
  • Adequate haematologic function and liver and renal function: neutrophils > 1.5×109/L; thrombocytes > 100×109/L; haemoglobin > 10 g/dl, creatinine clearance > 60 ml/min (calculated according to Cockroft and Gault), total bilirubin < 1.0×UNL; AST and ALT < 1.5×UNL, AP < 2.5×UNL
  • Complete staging within 3 weeks prior to start of treatment (CT-scan of thorax and abdomen, endosonography, gastroscopy)
  • Ability to keep appointments and follow the study protocol
  • By CT-scan, endoscopy or endosonography measurable or evaluable disease

Exclusion Criteria:

  • Former therapy of cancer (operation, chemo- or radiotherapy)
  • Diagnosis of another cancer in the last 5 years prior to study entry which has not been cured by operation only (exception in-situ-carcinoma of the cervix or cured non-melanomatose skin cancer)
  • Known contraindication to the planned chemotherapeutics
  • Presence of distant metastases
  • Anamnestic known serious disease or other concomitant diseases that affect participation in this study, such as:

oInstable cardiac disease: symptomatic heart failure, symptomatic coronary artery disease, ventricular cardiac arrhythmia not well controlled with medication, myocardial infarction or resuscitation within 6 month before study oActive infection necessitating systemic therapy or uncontrolled infection oInterstitial lung diseases (for example: pneumonitis or fibrosis of the lung) and indication for interstitial lung disease in chest x-ray or CT-scan respectively oActive inflammatory bowel disease or other bowel diseases which provoke chronic diarrhea (defined as > 4 bowel movements per day) oNeurological or psychiatric disease including dementia, epilepsy or untreated, symptomatic brain metastases oLimited hearing ability

  • Presence of upper GI obstruction, leading to inability to swallow ground tablets
  • Presence of acute or chronic systemic infection
  • Presence of a bowel obstruction within the last 30 days
  • Pregnant or lactating women or women with child bearing potential and men without adequate contraception (high effective contraception, defined as Pearl Index < 1) like birth control pill, hormone spiral, hormone implant, transdermal patch, a combination of two barrier methods (condom and diaphragm), realized sterilization or sexual abstinence during the study and at least for 3 months after the last infusion
  • Any other situation which may lead to an unacceptable high risk for the patient, when he participates in the study
  • Parallel treatment in another clinical study or prior participation in this study
  • Treatment with any other therapy against the tumor or any parallel radiation
  • Symptomatic peripheral neuropathy NCI-CTCAE degree > 2
  • Intolerance to the study medication
  • Detention in a psychiatric unit or imprisonment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Preoperative chemotherapy followed by surgery
Drug: Paclitaxel; Cisplatin; 5-Fluorouracil
Two preoperative cycles with Paclitaxel 200 mg/m² d1, Cisplatin 60 mg/m² d1, 5-Fluorouracil 700 mg/m² d1-5 repeated every 3 weeks followed by resection
ACTIVE_COMPARATOR: Perioperative chemotherapy with surgery
Drug: Paclitaxel; Cisplatin; 5-Fluorouracil
Two preoperative cycles with Paclitaxel 200 mg/m² d1, Cisplatin 60 mg/m² d1, 5-Fluorouracil 700 mg/m² d1-5 repeated every 3 weeks followed by resection
Drug: Paclitaxel; Cisplatin; 5-Fluorouracil; Capecitabine
Two postoperative cycles with Paclitaxel 200 mg/m²/day d1, Cisplatin 60 mg/m²/day d1, 5-Fluorouracil 700 mg/m²/day d1-5 repeated every 3 weeks Among patients with no responses to preoperative chemotherapy, Capecitabine 625 mg/m² twice-daily dose as alternatives to infused 5-Fluorouracil in the postoperative chemotherapy regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival
Time Frame: 3 years
3 years
Overall survival rate
Time Frame: 5 years
5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Operative and postoperative complication rate
Time Frame: Within 30 days after surgery
Within 30 days after surgery
Rate of local recurrences and metastasis
30-day mortality
Time Frame: After date of surgery
After date of surgery
Pathological remission rate
Time Frame: After 2 cycles of preoperative chemotherapy (2 month)
After 2 cycles of preoperative chemotherapy (2 month)
Resectability rate
Time Frame: After 2 cycles of preoperative chemotherapy (2 month)
After 2 cycles of preoperative chemotherapy (2 month)
Toxicity of preoperative and postoperative chemotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Health Science Center of Xi'an Jiaotong University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 1997

Primary Completion (ACTUAL)

December 1, 2008

Study Completion (ACTUAL)

January 1, 2010

Study Registration Dates

First Submitted

October 19, 2010

First Submitted That Met QC Criteria

October 20, 2010

First Posted (ESTIMATE)

October 21, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

October 21, 2010

Last Update Submitted That Met QC Criteria

October 20, 2010

Last Verified

September 1, 2010

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZY-01

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.

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