Irinotecan, Radiation Therapy, and Docetaxel With or Without Cisplatin in Treating Patients With Locally Advanced Esophageal Cancer

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00601692

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Irinotecan and docetaxel may also make tumor cells more sensitive to radiation therapy. Giving combination chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of docetaxel when given together with irinotecan and radiation therapy with or without cisplatin in treating patients with locally advanced esophageal cancer.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer	Drug: cisplatin Drug: docetaxel Drug: irinotecan hydrochloride Radiation: radiation therapy	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2003

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Regimen 1 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. 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.	Drug: docetaxel Given IV Drug: irinotecan hydrochloride Given IV Radiation: radiation therapy Given 5 days a week for 3 weeks
Experimental: Regimen 2 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. 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.	Drug: cisplatin Given IV Drug: docetaxel Given IV Drug: irinotecan hydrochloride Given IV Radiation: radiation therapy Given 5 days a week for 3 weeks

Arm

Intervention/Treatment

Experimental: Regimen 1

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. 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.

Drug: docetaxel

Given IV

Drug: irinotecan hydrochloride

Given IV

Radiation: radiation therapy

Given 5 days a week for 3 weeks

Experimental: Regimen 2

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. 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.

Drug: cisplatin

Given IV

Drug: docetaxel

Given IV

Drug: irinotecan hydrochloride

Given IV

Radiation: radiation therapy

Given 5 days a week for 3 weeks

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of docetaxel when administered together with irinotecan hydrochloride and radiotherapy [2 years]

Secondary Outcome Measures

Clinical and pathological complete response rate [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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