Testing TH-302, in Combination With Preoperative Chemoradiotherapy, in Esophageal Cancer.
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02598687|
Recruitment Status : Withdrawn (2 Phase 3 trials didn't meet their primary endpoint, so further development and testing of TH-302 is uncertain)
First Posted : November 6, 2015
Last Update Posted : April 21, 2016
|Condition or disease||Intervention/treatment||Phase|
|Esophageal Cancer||Drug: TH-302 Other: HX4 scan Drug: Carboplatin Drug: Paclitaxel Radiation: Radiotherapy Procedure: surgery||Phase 1|
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.
• 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).
- 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||December 2015|
|Actual Primary Completion Date :||April 2016|
|Actual Study Completion Date :||April 2016|
treatment arm: TH-302 pre-treatment day 4 and weekly during treatment. 5 x carboplatin and paclitaxel, radiotherapy: 23 x 1.8Gy HX4 scans day 1 and day 8,surgery 6-10 weeks after chemo-radiotherapy
TH-302 day 4 (pre-treatment) and weekly during chemo-radiotherapy (CRT)
Other: HX4 scan
HX 4 scan day 1 and day 8
23 x 1.8 Gy
minimally invasive transhiatal approach including a one-field node dissection or transthoracic approach with a two-field lymph node dissection
- Dose Limiting Toxicity (DLT ) [ Time Frame: within 30days postoperative ]To determine the DLT and define the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
- hypoxia response in tumor [ Time Frame: day 4 and day 8 ]Presence of hypoxia response based on hypoxia imaging (HX4) at baseline and first administration of TH-302 (before chemoradiotherapy).
- rate of pathological Complete Remission (pCR) [ Time Frame: within 30 days after surgery ]Presence of anti-tumor activity measured by the rate of pathological Complete Remission (pCR)
- histopathologic negative circumferential resection margin (CRM) rate [ Time Frame: within 30 days after surgery ]Presence of anti-tumor activity measured by histopathologic negative circumferential resection margin (CRM) rate.
- Local recurrence rate [ Time Frame: within 30 days after surgery ]Presence of anti-tumor activity measured by local recurrence rate
- distance recurrence rate [ Time Frame: within 30 days after surgery ]Presence of anti-tumor activity measured by distance recurrence rate
- Progression free survival [ Time Frame: within 30 days after surgery ]Presence of anti-tumor activity measured by progression free survival
- overall survival [ Time Frame: within 30 days after surgery ]Presence of anti-tumor activity measured by overall survival
- metabolic response [ Time Frame: within 30 days after surgery ]Presence of anti-tumor activity measured by metabolic response one month after treatment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02598687
|Principal Investigator:||Philippe Lambin, MD, PhD||MUMC+, dept Radiotherapy|