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A Phase II Study to Assess the Efficacy of Combined Pre-operative Chemo (CPT11, Cisplatin), Radiotherapy (External Beam, Brachytherapy), Plus Surgery for Potentially Resectable Thoracic Esophageal Cancer

Phase 2/Phase 3
18 Years
Not Enrolling
Esophageal Cancer

Thank you

Trial Information

A Phase II Study to Assess the Efficacy of Combined Pre-operative Chemo (CPT11, Cisplatin), Radiotherapy (External Beam, Brachytherapy), Plus Surgery for Potentially Resectable Thoracic Esophageal Cancer

Historical surgical series have reported that the chance of cure with surgery alone is
approximately one in four. Many phase II studies and some phase III studies have examined
the role of induction (preoperative) chemotherapy and radiation. In general, these studies
have demonstrated a trend to improved survival using an induction regimen with one phase III
study reporting a significant improvement in survival. Two meta-analyses have failed to
demonstrate a clear advantage of an induction regimen.

When these trials are reviewed, it is apparent that there is a subgroup of patients who are
found at the time of resection to have had a complete pathological response to their
treatment, and these patients clearly experience improved survival.

These previous trials have used older chemotherapy agents. Nevertheless, cisplatin remains
one of the most active drugs available for treating solid tumours. Irinotecan is a newer
drug that has demonstrated significant activity in colorectal cancer and more recently in
esophageal cancer. A previous single institution trial of cisplatin and irinotecan in
esophageal cancer demonstrated a significant response and acceptable toxicity.

By giving one cycle of chemotherapy alone first, it is expected that the dysphagia usually
experienced by these patients will improve sufficiently and that nutritional support, i.e.
feeding tube, will not be required (as has been demonstrated in a previous study of this
drug combination). The same drugs will then be given concurrently with external beam
radiation in order to take advantage of the radiosensitizing properties of both these drugs.

This will be followed by a boost dose of radiation, which will provide a total dose in the
tumourcidal range. Surgery will follow the boost dose of radiation.

This study proposes to combine two drugs with demonstrated activity in esophageal cancer,
cisplatin and Irinotecan, with radiation prior to surgery, with the hypothesis that these
more active agents will offer better control of distant metastatic disease. Their
radiosensitizing properties, when combined with radiation, will improve local control and
provide an increased rate of pathological complete response in patients with surgically
resectable esophageal cancer.

Inclusion Criteria:

- Histologically proven squamous or adenocarcinoma or the esophagus >20 cm from the
incisors, including GE junction tumors (unless of gastric origin). GE junction
tumors are defined as tumors that have their center within 5 cm proximal and distal
of the anatomical cardia

- Clinical T1 N1 M0, T2-3 N0-1 M0, T1-3 N0-1 M1a

- Performance status ECOG 0-2

- Medically fit for chemotherapy, radiation and esophagectomy

- Adequate bone marrow, hepatic and renal function as evidenced by the following:


Neutrophils > 1.5 x 109/L Platelets > 100 x 109/L

Hepatic function:

Total bilirubin < 1.25x ULN AST (SGOT) and ALT (SGPT) < 2.5 x ULN Alkaline phosphatase
<2.5 x ULN

Renal function:

Serum creatinine < 160 umol/L or creatinine clearance > 60 ml/min (actual or calculated by
the Cockcroft-Gault method as follows):

weight (kg) x (140 - age) K x serum creatinine*

- for serum creatinine in *mol/L, K=0.814 in man, K=0.96 in woman

- No prior history of malignancy unless > 5 years disease free, or adequately
treated nonmelanotic skin cancer or in situ carcinoma of the cervix

- Tumor technically resectable (as defined in Section 5.4.3)

Exclusion Criteria:

- In situ or clinical T1N0M0

- Cervical esophageal tumors (within 20 cm of the incisors)

- Positive cytology of the pleura, peritoneum or pericardium

- Supraclavicular lymph node involvement

- Invasion of tracheobronchial tree proven by bronchoscopy including but not limited to
tracheo-esophageal fistula

- Prior treatment for this malignancy except esophageal stenting

- Gilbert's disease

- Age < 18

- Participation in another concurrent clinical study involving study drug(s) or
treatment with study drug within thirty days prior to the treatment on this study.
Concurrent treatment with other experimental drugs or anticancer therapy

- Known hypersensitivity to either of study drugs or to any of their excipients.

- Pregnant or lactating women. Men and women of reproductive potential (and women < 12
months after menopause) may not participate unless they have agreed to use an
effective contraceptive method while on study

- Known or suspected alcohol or drug abuse

- Other serious or concurrent illnesses that may interfere with subject compliance,
adequate informed consent, determination of causality of adverse events and which in
the judgement of the Investigator, would make the patient inappropriate for entry
into the study

- Life expectancy < 3 months

- Peripheral neuropathy > Grade 2 (using CTC Version 2)

- Patients receiving phenytoin or phenobarbital

Type of Study:


Study Design:

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

Outcome Measure:

pathological complete response

Outcome Time Frame:

1 day

Safety Issue:


Principal Investigator

Darling E Gail, M.D., FRCSC

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Health Network, Toronto


Canada: Health Canada

Study ID:




Start Date:

April 2009

Completion Date:

March 2011

Related Keywords:

  • Esophageal Cancer
  • esophageal
  • esophagus
  • irinotecan
  • CPT11
  • cisplatin
  • Esophageal Diseases
  • Esophageal Neoplasms