Clinical trial NCT00354679
Conditions: Esophageal Cancer
Keywords: adenocarcinoma of the esophagus recurrent esophageal cancer stage III esophageal cancer stage II esophageal cancer
Sponsor: Memorial Sloan Kettering Cancer Center
Start date: 2006-04-01; Completion date: 2015-06-01
Enrollment: 34 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of esophageal cancer by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and monoclonal antibody therapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bevacizumab after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving irinotecan, cisplatin, and bevacizumab together with radiation therapy followed by surgery and bevacizumab works in treating patients with locally advanced esophageal cancer.

Detailed description:
OBJECTIVES:

Primary

* Evaluate the toxicity and safety of bevacizumab when given together with cisplatin, irinotecan hydrochloride, and radiotherapy followed by surgery and adjuvant bevacizumab in patients with locally advanced esophageal adenocarcinoma.

Secondary

* Observe the rate of pathologic complete response in patients treated with this regimen.
* Observe overall survival, disease-free survival, and patterns of failure in these patients.
* Clarify toxicity and tolerability of this regimen.
* Evaluate pre-treatment levels of vascular endothelial growth factor in patient serum as a corollary of response to this regimen.
* Correlate serum proteomics data with complete pathologic response.

OUTLINE: This is a nonrandomized, open-label study.

* Induction therapy: Patients receive cisplatin IV over 30 minutes and irinotecan hydrochloride IV over 30 minutes on days 1, 8, 22, and 29. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 22.
* Combination therapy and radiotherapy: Patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 43, 50, 64, and 71. Patients also receive bevacizumab IV over 30-90 minutes on days 43 and 64. Patients undergo external beam radiotherapy 5 days a week for 6 weeks beginning on day 43.
* Surgery: Patients undergo surgery 6-8 weeks after finishing combination therapy and radiotherapy.
* Maintenance therapy: Approximately 6 weeks after surgery, patients receive bevacizumab IV over 30-90 minutes every 3 weeks for 6 months.

Blood samples are obtained at baseline, after finishing chemoradiotherapy, and prior to maintenance therapy and are examined by the matrix-assisted laser-desorption ionization time of flight (MALDI-TOF) mass spectometry for proteomic profiling.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

Arms: arm 1: Induction therapy: Patients receive cisplatin IV over 30 minutes and irinotecan hydrochloride IV over 30 minutes on days 1, 8, 22, and 29. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 22.

Combination therapy and radiotherapy: Patients receive cisplatin and irinotecan hydrochloride as in induction chemotherapy on days 43, 50, 64, and 71. Patients also receive bevacizumab IV over 30-90 minutes on days 43 and 64. Patients undergo external beam radiotherapy 5 days a week for 6 weeks beginning on day 43. Surgery: Patients undergo surgery 6-8 weeks after finishing combination therapy and radiotherapy.

Maintenance therapy: Approximately 6 weeks after surgery, patients receive bevacizumab IV over 30-90 minutes every 3 weeks for 6 months
Interventions: intervention 1: bevacizumab intervention 2: cisplatin intervention 3: irinotecan hydrochloride intervention 4: proteomic profiling intervention 5: diagnostic laboratory biomarker analysis intervention 6: mass spectrometry intervention 7: adjuvant therapy intervention 8: neoadjuvant therapy intervention 9: therapeutic conventional surgery intervention 10: radiation therapy
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None intervention 7: None intervention 8: None intervention 9: None intervention 10: None

Protocol documents: