NCT02598687

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

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• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Maastricht Radiation Oncology · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Esophageal Cancer

Interventions

Type	Name	Description
DRUG	TH-302	TH-302 day 4 (pre-treatment) and weekly during chemo-radiotherapy (CRT)
OTHER	HX4 scan	HX 4 scan day 1 and day 8
DRUG	Carboplatin	2mg/ml/min
DRUG	Paclitaxel	50 mg/m2
RADIATION	Radiotherapy	23 x 1.8 Gy
PROCEDURE	surgery	minimally invasive transhiatal approach including a one-field node dissection or transthoracic approach with a two-field lymph node dissection

Timeline

• Start date: 2015-12-01
• Primary completion: 2016-04-01
• Completion: 2016-04-01
• First posted: 2015-11-06
• Last updated: 2016-04-21