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

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00601692

Purpose

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	Intervention	Phase
Esophageal Cancer	Drug: cisplatin Drug: docetaxel Drug: irinotecan hydrochloride Radiation: radiation therapy	Phase I

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders Radiation Therapy

Drug Information available for: Cisplatin Irinotecan U 101440E Docetaxel Irinotecan hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Trial of Irinotecan, Radiation Therapy and Escalating Doses of Docetaxel With Cisplatin in Locally Advanced Esophageal Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of docetaxel when administered together with irinotecan hydrochloride and radiotherapy [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Clinical and pathological complete response rate [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	April 2003
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Regimen 1: Experimental 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
Regimen 2: Experimental 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

Arms

Assigned Interventions

Regimen 1: Experimental

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

Regimen 2: Experimental

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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00601692

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: David H. Ilson, MD, PhD 212-639-8306

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

David H. Ilson, MD, PhD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000582309, MSKCC-02061, SANOFI-AVENTIS-MSKCC-02061
Study First Received:	January 17, 2008
Last Updated:	April 30, 2009
ClinicalTrials.gov Identifier:	NCT00601692 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

squamous cell carcinoma of the esophagus
adenocarcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer

Study placed in the following topic categories:

Digestive System Neoplasms
Gastrointestinal Diseases
Esophageal Neoplasms
Irinotecan
Esophageal Cancer
Squamous Cell Carcinoma
Camptothecin
Carcinoma
Docetaxel
Digestive System Diseases

Radiation-Sensitizing Agents
Cisplatin
Esophageal Disorder
Head and Neck Neoplasms
Epidermoid Carcinoma
Gastrointestinal Neoplasms
Esophageal Diseases
Carcinoma, Squamous Cell
Adenocarcinoma
Antineoplastic Agents, Phytogenic

Additional relevant MeSH terms:

Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Esophageal Neoplasms
Physiological Effects of Drugs
Irinotecan
Enzyme Inhibitors
Pharmacologic Actions
Camptothecin
Docetaxel

Neoplasms
Digestive System Diseases
Neoplasms by Site
Radiation-Sensitizing Agents
Cisplatin
Therapeutic Uses
Head and Neck Neoplasms
Gastrointestinal Neoplasms
Esophageal Diseases
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 06, 2009