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A Phase I Trial of Irinotecan, Radiation Therapy and Escalating Doses of Docetaxel With Cisplatin in Locally Advanced Esophageal Cancer


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

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Trial Information

A Phase I Trial of Irinotecan, Radiation Therapy and Escalating Doses of Docetaxel With Cisplatin in Locally Advanced Esophageal Cancer


OBJECTIVES:

Primary

- To determine the dose limiting toxicity and recommended phase II dose of docetaxel when
given at escalating doses with weekly irinotecan hydrochloride and concurrent
radiotherapy in patients with locally advanced esophageal cancer.

- To determine the dose limiting toxicity of cisplatin, once the recommended phase II
dose of docetaxel is established, when given weekly with docetaxel, irinotecan
hydrochloride, and concurrent radiotherapy in patients with locally advanced esophageal
cancer.

Secondary

- To evaluate the clinical and pathological complete response rate in patients with
locally advanced esophageal cancer treated with induction chemotherapy comprising
docetaxel and irinotecan hydrochloride with or without cisplatin followed by concurrent
docetaxel and irinotecan hydrochloride with or without cisplatin plus radiotherapy.

OUTLINE: Patients receive one of the following regimens. Regimen 2 is for patients recruited
after the recommended phase II dose has been determined in patients recruited (who receive
regimen 1).

- Regimen 1:

- Induction chemotherapy (weeks 1-6): Patients receive docetaxel IV over 15 minutes
and irinotecan hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats
every 3 weeks for 2 courses in the absence of disease progression or unacceptable
toxicity.

- Chemoradiotherapy (weeks 8-13): Beginning in week 8, patients receive docetaxel IV
over 15 minutes and irinotecan hydrochloride IV over 30 minutes on days 1 (week 8)
and 8 (week 9). Patients also undergo radiotherapy once daily, 5 days a week, in
weeks 8-10. Treatment with chemoradiotherapy repeats every 3 weeks for 2 courses
in the absence of disease progression or unacceptable toxicity.

- Regimen 2:

- Induction chemotherapy (weeks 1-6): Patients receive docetaxel IV and irinotecan
hydrochloride as in regimen 1 induction chemotherapy. They also receive cisplatin
IV over 20-30 minutes on days 1 and 8. Treatment with irinotecan hydrochloride,
docetaxel, and cisplatin repeats every 3 weeks for 2 courses in the absence of
disease progression or unacceptable toxicity.

- Chemoradiotherapy (weeks 8-13): Patients receive docetaxel IV, irinotecan
hydrochloride IV, and undergo radiotherapy as in regimen 1 chemoradiotherapy.
Patients also receive cisplatin IV over 20-30 minutes on days 1 (week 8) and 8
(week 9). Treatment with irinotecan hydrochloride, docetaxel, cisplatin, and
radiotherapy repeats every 3 weeks for 2 courses in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 3 years, and then annually thereafter.

Inclusion Criteria


DISEASE CHARACTERISTICS:

Inclusion criteria:

- Histologically confirmed squamous cell carcinoma, adenocarcinoma, poorly
differentiated carcinoma, or carcinoma not otherwise specified, of the esophagus or
gastroesophageal (GE) junction

- Disease clinically limited to the esophagus or GE junction (T1, N1, M0, or T2-4,
any N, M0)

- M1a metastatic disease to lymph nodes allowed

- Includes celiac lymph nodes in a patient with a distal third esophageal
primary lesion or a gastroesophageal junction primary or supraclavicular
lymph nodes in a patient with a proximal third esophageal lesion

- Disease must be able to be contained in a radiotherapy field

- Previously untreated patients with primary tumors of the cervical or thoracic
esophagus, including the GE junction, are eligible for this study

- At least 50% of the tumor must involve the distal esophagus for tumors of the GE
junction

Exclusion criteria:

- Positive malignant cytology of the pleura, pericardium, or peritoneum

- Metastatic disease to distant organs (e.g. liver) or non-regional lymph nodes

- Biopsy proven tumor invasion of the tracheobronchial tree or tracheo-esophageal
fistula

PATIENT CHARACTERISTICS:

Inclusion criteria:

- Karnofsky performance status (PS) 70-100% OR ECOG PS 0-2

- ANC ≥ 1,500 cells/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9.0 mg/dL

- Creatinine ≤ 1.5 mg/dL

- Total serum bilirubin ≤ 1.0 mg/dL

- AST ≤ 1.5 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 2.5 times ULN

- Men and women of child bearing potential must use effective contraception while on
treatment and for a reasonable period thereafter

- Negative pregnancy test

Exclusion criteria:

- History of severe hypersensitivity reaction to docetaxel or other drugs formulated
with polysorbate 80

- Pre-existing peripheral neuropathy > grade 1

- Severe comorbid conditions including, but not limited to, any of the following:

- NYHA class III-IV cardiac disease

- Myocardial infarction within the past 6 months

- Severe uncontrolled diabetes

- Hypercalcemia

- Uncontrolled hypertension

- Cerebral vascular disease

- Uncontrolled infections

- Pregnant or lactating women

- History of prior malignancy diagnosed and/or treated within the past three years,
except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of
the cervix, or superficial transitional cell carcinoma of the bladder

- Known Gilbert disease

- History of seizure disorder with concurrent phenytoin, phenobarbital, or other
antiepileptic medication

- Any other concurrent medical or psychiatric condition or disease that, in the
investigator's judgment, would make the patient inappropriate for entry into this
study

- Patients who cannot fully comprehend the therapeutic implications of the protocol or
comply with the requirements

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy or radiotherapy (RT) for this esophageal cancer

- No prior mantle RT, chest RT, pelvic RT, or hemi-body RT

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum tolerated dose of docetaxel when administered together with irinotecan hydrochloride and radiotherapy

Outcome Time Frame:

2 years

Safety Issue:

Yes

Principal Investigator

David H. Ilson, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

02-061

NCT ID:

NCT00601692

Start Date:

April 2003

Completion Date:

December 2009

Related Keywords:

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

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021