NCT01183559

A Trial of ZD6474, Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiation Therapy Followed by Surgery

Induction Therapy for Locally Advanced, Resectable Cancer of the Esophagus, Gastroesophageal (GE) Junction and Gastric Cancer: A Phase I Trial of ZD6474 (Zactima, Vandetanib), Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiation Therapy Followed by Surgery

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Fox Chase Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Conditions

• Cancer of the Esophagus
• Adenocarcinoma of the Gastroesophageal Junction
• Cancer of the Stomach

Interventions

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

Timeline

• Start date: 2008-08-07
• Primary completion: 2010-11-01
• Completion: 2011-08-01
• First posted: 2010-08-17
• Last updated: 2021-01-22
• Results posted: 2021-01-22

Locations

1 site across 1 country: United States