Clinical trial NCT00109850
Conditions: Esophageal Cancer
Keywords: adenocarcinoma of the esophagus squamous cell carcinoma of the esophagus stage III esophageal cancer
Sponsor: SWOG Cancer Research Network
Start date: 2005-05-01; Completion date: 2012-05-01
Enrollment: 22 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of esophageal cancer by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cetuximab together with combination chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy and radiation therapy works in treating patients with locally advanced esophageal cancer that cannot be removed by surgery.

Detailed description:
OBJECTIVES:

Primary

* Determine the 2-year overall survival of patients with previously untreated, clinically unresectable, locally advanced squamous cell carcinoma or adenocarcinoma of the esophagus treated with cetuximab, cisplatin, irinotecan, and thoracic radiotherapy.

Secondary

* Determine the toxicity profile of this regimen in these patients.
* Determine the probability of objective response (confirmed and unconfirmed, complete and partial) in patients with measurable disease treated with this regimen.
* Determine the time to progression in patients with measurable disease treated with this regimen.
* Correlate, preliminarily, gene expression (RNA) levels and germline polymorphisms of genes involved in DNA repair (e.g., ECRCC-1 and XRCC-1), drug metabolism (e.g., UGT1A1), and the epidermal growth factor receptor (EGFR) pathway (e.g., EGFR, interleukin-8, and vascular endothelial growth factor) with response, time to progression, overall survival, and toxicity in patients treated with this regimen. (This will not be completed as this study was closed due to poor accrual.)

OUTLINE: This is a multicenter study.

Patients receive cetuximab intravenous (IV) over 1-2 hours on days 1, 8, and 15. Patients also receive cisplatin IV and irinotecan IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of course 3, patients undergo thoracic radiotherapy once daily 5 days a week for 5-6 weeks (total of 28 treatments).

After completion of study treatment, patients are followed at 4 weeks and then every 3-6 months for up to 5 years after study entry.

PROJECTED ACCRUAL: A total of 75-100 patients (75 with adenocarcinoma and 25 with squamous cell carcinoma) will be accrued for this study.

Arms: arm 1: Cetuximab+Cisplatin+Irinotecan followed by radiation therapy (RT) in Cycle 3.
Interventions: intervention 1: cetuximab intervention 2: cisplatin intervention 3: irinotecan hydrochloride intervention 4: radiation therapy
Intervention descriptions: intervention 1: 400mg/m\^2 loading dose, intravenous (IV) over 120 min, day 1 of cycle 1 only. 250mg/m\^2 maintenance dose, IV over 60 min, Days 8 \& 15 of Cycle 1 and Days 1, 8, and 15 of subsequent cycles. intervention 2: 30mg/m\^2, bolus intravenous (IV), on Days 1 \& 8 of each cycle. intervention 3: 65mg/m\^2, intravenous (IV) over 30 min, on Days 1 \& 8 of each cycle. intervention 4: The total dose to the prescription point will be 5,040 cGy given in 28 fractions. The patient will be treated with one fraction per day with all fields treated per day. 180 cGy will be delivered to the isocenter. The dose variation in the planning target volume (PTV) will be +7% and -5% of the prescription point dose.

Protocol documents: