Text Size

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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00601692
First received: January 17, 2008
Last updated: March 21, 2013
Last verified: March 2013
History of Changes
  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 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose of docetaxel when administered together with irinotecan hydrochloride and radiotherapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical and pathological complete response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 27
Study Start Date: April 2003
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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
New York, New York, United States, 10065
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

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00601692     History of Changes
Other Study ID Numbers: 02-061, P30CA008748, MSKCC-02061, SANOFI-AVENTIS-MSKCC-02061
Study First Received: January 17, 2008
Last Updated: March 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
squamous cell carcinoma of the esophagus
adenocarcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer

Additional relevant MeSH terms:
Esophageal Diseases
Esophageal Neoplasms
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Irinotecan
Docetaxel
Cisplatin
 Camptothecin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013