Clinical trial NCT00005638: Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Esophageal Cancer
Official title: Phase I Trial of Combined Modality Irinotecan, Cisplatin, and Concurrent Radiation Therapy for Patients With Locally Advanced Esophageal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Esophageal Cancer
Gastric Cancer
Keywords: stage II gastric cancer
stage III gastric cancer
stage II esophageal cancer
stage III esophageal cancer
adenocarcinoma of the stomach
squamous cell carcinoma of the esophagus
adenocarcinoma of the esophagus
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of chemotherapy plus radiation therapy in treating patients who have advanced cancer of the esophagus.

Detailed description: OBJECTIVES:

* Determine the dose limiting toxicity of irinotecan when given weekly with cisplatin and concurrent external beam multifield radiotherapy in patients with locally advanced carcinoma of the esophagus or gastroesophageal junction.
* Determine the maximum tolerated dose and the recommended phase II dose of irinotecan in this regimen in this patient population.
* Evaluate the complete response rate in these patients to one course of induction chemotherapy followed by concurrent chemotherapy and radiotherapy.

OUTLINE: This is a dose escalation study of irinotecan.

Patients receive induction chemotherapy with cisplatin IV over 30 minutes followed by irinotecan IV over 30 minutes on days 1, 8, 15, and 22. Following 2 weeks of rest, patients begin chemoradiation. Patients receive cisplatin and irinotecan as above on days 1, 8, 22, and 29 and radiotherapy once daily 5 days a week for 5-6 weeks.

Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.

Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction

  * T1, N1, M0 or T2-4, Nx, M0

    * No supraclavicular or celiac lymph nodes
* Previously untreated, newly diagnosed tumors OR
* Prior resection without adjuvant therapy with local regional failure

  * Positive microscopic margin on resection of all gross disease allowed provided no metastatic disease
* No positive malignant cytology of the pleura, pericardium, or peritoneum
* No biopsy proven tumor invasion of the tracheobronchial tree or tracheoesophageal fistula

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 70-100% OR
* ECOG 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil count greater than 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 9.0 g/dL

Hepatic:

* Bilirubin no greater than 1.5 mg/dL
* No known Gilbert's disease

Renal:

* Creatinine no greater than 1.5 mg/dL
* No hypercalcemia

Cardiovascular:

* No New York Heart Association class III or IV heart disease
* No myocardial infarction within the past 6 months
* No uncontrolled hypertension

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other severe concurrent conditions (e.g., severe uncontrolled diabetes, uncontrolled infections, or cerebral vascular disease)
* No other malignancy within the past 5 years except basal cell carcinoma of the skin or carcinoma in situ of the cervix
* No history of seizure disorder currently receiving phenytoin, phenobarbital, or other antiepileptic medication
* No other concurrent medical or psychiatric condition or disease that would preclude study entry

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy for esophageal cancer including adjuvant chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy for esophageal cancer including adjuvant radiotherapy
* No prior mantle, chest, pelvic, or hemibody radiotherapy

Surgery:

* See Disease Characteristics

Other:

* No concurrent prochlorperazine on day of irinotecan administration

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: David H. Ilson, MD, PhD
role: STUDY_CHAIR
References:
citation: Ilson DH, Bains M, Kelsen DP, O'Reilly E, Karpeh M, Coit D, Rusch V, Gonen M, Wilson K, Minsky BD. Phase I trial of escalating-dose irinotecan given weekly with cisplatin and concurrent radiotherapy in locally advanced esophageal cancer. J Clin Oncol. 2003 Aug 1;21(15):2926-32. doi: 10.1200/JCO.2003.02.147.