Vandetanib, Oxaliplatin, and Docetaxel in Advanced Cancer of the Esophagus or Gastroesophageal Junction

Esophageal Cancer Clinical Trial

Official title: Phase I/II Study of the Combination of Oxaliplatin / Docetaxel and ZACTIMA for the Treatment of Advanced Cancers of the Esophagus and Gastroesophageal Junction

Status Terminated

Clinical Trial Summary

RATIONALE: Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as oxaliplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether vandetanib is more effective than a placebo when given together with oxaliplatin and docetaxel in treating advanced cancer of the esophagus or gastroesophageal junction.

PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of vandetanib when given together with oxaliplatin and docetaxel and to see how well it works in treating patients with advanced cancer of the esophagus or gastroesophageal junction.

Clinical Trial Description

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of vandetanib when administered with oxaliplatin and docetaxel in patients with advanced cancer of the esophagus or gastroesophageal junction. (Phase I)

• To evaluate the toxicity of this regimen in these patients. (Phase I)

• To determine the progression-free survival of these patients. (Phase II)

Secondary

• To determine the response rate in patients treated with oxaliplatin and docetaxel with or without vandetanib. (Phase II)

• To determine the overall survival of patients treated with these regimens. (Phase II)

• To determine the toxicity of these regimens in these patients. (Phase II)

• To determine whether tumor characteristics (e.g., EGFR/ErbB2 expression, activation and mutational status of the EGFR and ErbB2 pathway [total and phosphorylated EGFR and ErbB2, mutational and FISH analysis] and tumoral expression of HIF1-alpha) may have an association with response and outcome. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of vandetanib followed by a randomized phase II study.

Patients are stratified according to histology (adenosarcoma vs squamous cell carcinoma) and prior neoadjuvant/adjuvant chemotherapy/chemoradiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms. Patients in phase I receive treatment as in phase II arm I.

• Phase II arm I: Patients receive docetaxel IV over 1 hour on days 1 and 8, oxaliplatin IV over 2 hours on day 1, and oral vandetanib (at the maximum tolerated dose determined in phase I) once daily on days 1-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease may continue to receive vandetanib beyond 8 courses in the absence of disease progression or unacceptable toxicity.

• Phase II arm II: Patients receive docetaxel and oxaliplatin as in arm I. Patients also receive an oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease may continue to receive vandetanib beyond 8 courses in the absence of disease progression or unacceptable toxicity.

Patients enrolled in phase II submit baseline tumor tissue samples for correlative laboratory studies, including analysis of EGFR and ErbB2 by mutational, FISH, and IHC analysis and HIF1-alpha expression by IHC analysis. ;

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gastroesophageal Junction
• Esophageal Cancer
• Esophageal Neoplasms

• NCT number: NCT00732745
• Study type: Interventional
• Source: Case Comprehensive Cancer Center
• Status: Terminated
• Phase: Phase 1
• Start date: October 2008