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

Primary Purpose

Esophageal Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cisplatin
docetaxel
irinotecan hydrochloride
radiation therapy
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring squamous cell carcinoma of the esophagus, adenocarcinoma of the esophagus, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

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

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Regimen 1

Regimen 2

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Clinical and pathological complete response rate

Full Information

First Posted
January 17, 2008
Last Updated
March 21, 2013
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00601692
Brief Title
Irinotecan, Radiation Therapy, and Docetaxel With or Without Cisplatin in Treating Patients With Locally Advanced Esophageal Cancer
Official Title
A Phase I Trial of Irinotecan, Radiation Therapy and Escalating Doses of Docetaxel With Cisplatin in Locally Advanced Esophageal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
April 2003 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Cancer
Keywords
squamous cell carcinoma of the esophagus, adenocarcinoma of the esophagus, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Regimen 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Regimen 2
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
docetaxel
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
Given 5 days a week for 3 weeks
Primary Outcome Measure Information:
Title
Maximum tolerated dose of docetaxel when administered together with irinotecan hydrochloride and radiotherapy
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Clinical and pathological complete response rate
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David H. Ilson, MD, PhD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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