Conditions: Cancer of the Esophagus Adenocarcinoma of the Gastroesophageal Junction Cancer of the Stomach
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 9
Healthy volunteers: no

Brief summary:
The purpose of the study is to determine the most tolerable and safe dose of ZD6474 (Zactima, Vandetanib) when given with standard chemotherapy, radiation therapy and surgery in patients with cancer of the esophagus

Detailed description:
Epidermal Growth Factor Receptor (EGFR) is known to be an important prognostic factor for patients with esophageal cancer-overexpression is associated with a worse prognosis. Review of the literature demonstrates presence of EGFR expression in up 90% of cases of esophageal cancer. Additionally, Vascular Endothelial Growth factor (VEGF) is commonly overexpressed in esophageal cancer (especially adenocarcinoma) and is linked to the transition from Barrett's esophagus to invasive adenocarcinoma. Esophageal cancers with overexpression of VEGF are associated with a worse prognosis and poorer response to conventional chemoradiation.

Therefore, we feel it would be valuable to add an inhibitor of EGFR and VEGFR to the therapy of esophageal cancer to increase the rate of pathologic complete response and thus improve overall survival. In current trials of ZD6474 in combination with chemotherapy, the dose has been 300mg. We will perform a phase I trial in which we will dose-escalate ZD6474 to determine if this drug is tolerable in combination with cytotoxic chemotherapy and external beam radiation therapy. This would be the first trial in humans in which f these three modalities would be combined. We will determine the maximum tolerated dose of ZD6474 in this small trial and then hope to perform a larger phase II trial, perhaps in the context of the Radiation Therapy Oncology Group (RTOG).

Arms:
arm 1: Vandetanib 100 mg (6 patients) or 200 mg (3 patients) orally daily during the conventional 3D-guided conformal radiation therapy plus chemotherapy with carboplatin (AUC 5) on days 1 and 29, paclitaxel 50 mg/m2 i.v. weekly on days 1, 8, 15, 22, 29; and continuous infusion of 5-fluorouracil at 225 mg/m2 for 96 hours Monday-Friday during the radiation.

Interventions: intervention 1: Vandetanib intervention 2: 5 Fluorouracil (FU) intervention 3: Carboplatin intervention 4: Paclitaxel intervention 5: External Beam Radiation Therapy (RT)
Intervention descriptions: intervention 1: Vandetanib 100mg orally escalating to doses of 200 mg daily 7 days a week until completion of radiation therapy intervention 2: 5-FU 225 mg/m2/day continuous infusion over96 hours during radiation therapy intervention 3: Carboplatin AUC=5 days 1 and 29 during radiation therapy intervention 4: Paclitaxel 50 mg/m2 days 1, 8, 15, 22, 29 during radiation therapy intervention 5: External Beam Radiation Therapy(XRT)to a total dose of 4,500 centiGray (cGy) (180 cGy fractions daily) Monday through Friday for five weeks

Protocol document: