Testing TH-302, in Combination With Preoperative Chemoradiotherapy, in Esophageal Cancer.

Esophageal Cancer Clinical Trial

Official title: A Phase I Trial Testing TH-302, a Tumor-selective Hypoxia-Activated Cytotoxic Prodrug, in Combination With Preoperative Chemoradiotherapy in Patients With Distal Esophageal and Esophago-gastric Junction Adenocarcinoma

Status Withdrawn

Clinical Trial Summary

Open-label, single-center phase 1 study of an investigational agent TH-302 and standard chemoradiotherapy with a 3+3 dose escalation design through 3 dose levels.

Clinical Trial Description

Rationale:

Neoadjuvant chemoradiotherapy followed by surgery remains the standard of care for esophageal cancer patients. Both limited local response as well as distant metastases are a common cause of treatment failure. Combining TH-302 with chemo-radiotherapy may improve outcome by:

• Direct cytotoxic effect of TH-302 on hypoxic cells of the primary tumor without enhancing normal tissue toxicity.

• Increase the sensitivity of the primary tumor to chemo-radiotherapy by decreasing the hypoxic fraction.

• A bystander cytotoxic effect of TH-302 on normoxic cells adjacent to hypoxic cells of the primary tumor.

• A potential cytotoxic effect on micro-metastasis.

Objective:

Primary objective

• To determine Maximum Tolerated Dose (MTD) of TH-302 combined with chemoradiotherapy (23 x 1.8 Gy in combination with Carboplatin and Paclitaxel) in patients with distal esophageal or esophago-gastric junction adenocarcinoma, and consequently find the recommended phase II dose (RP2D).

Secondary objective

• To explore the prognostic and predictive value on outcome of the repeated hypoxia PET/CT-scan at baseline and after administration of TH-302 (before start of RCT).

• To determine presence of anti-tumor activity with TH-302 administration.

• To explore the relationship between tumor hypoxia detected by the HX4 PET/CT-scans and serum biomarker expression: CAIX and Osteopontin expression.

Study design: Open-label, single-center phase 1 study of an investigational agent TH-302 and standard chemoradiotherapy with a 3+3 dose escalation design through 3 dose levels.

Number of patients: 9 to18. For each of the 3 dose steps, 3 to 6 patients will be included. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

• NCT number: NCT02598687
• Study type: Interventional
• Source: Maastricht Radiation Oncology
• Status: Withdrawn
• Phase: Phase 1
• Start date: December 2015
• Completion date: April 2016