WithdrawnNCT02598687Updated Apr 21, 2016

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

A Phase 1 interventional study of TH-302 and HX4 scan in Esophageal Cancer, sponsored by Maastricht Radiation Oncology. Withdrawn. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-04-21.

Sponsored by Maastricht Radiation Oncology · Phase 1, Interventional, and Treatment

Why this study was withdrawn

2 Phase 3 trials didn't meet their primary endpoint, so further development and testing of TH-302 is uncertain

Phase: Phase 1
Study type: Interventional
Enrollment: 0
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study 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.

Read the 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 studied

Esophageal Cancer

Browse trials for

Esophageal Neoplasms 1,631

In context

Esophageal Neoplasms

1,631 studies on the registry are indexed under Esophageal Neoplasms; 469 are open to participants now.

Browse Esophageal Neoplasms studies →

Lead sponsor

Maastricht Radiation Oncology is the lead sponsor of 106 studies on the registry; 9 are open to participants now.

Browse Maastricht Radiation Oncology studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Histologically proven adenocarcinoma of the esophagus
Age >18 years
UICC T2-4 N0-2 M0, potentially resectable disease
Patient discussed at tumour board (multidisciplinary team meeting)
No evident tumor invasion in nearby regions like aorta or trachea
WHO performance status 0-2
Less than 10 % weight loss in the past 6 months
Laboratory requirements within 7 days prior to enrollment (start chemoradiotherapy):
Haematology:
- haemoglobin >10g/dl
- absolute neutrophils ≥ 1.5 x 109/L
- platelets ≥ 100x109/L
Biochemistry:
- bilirubin within institutional normal limits
- AST(SGOT)/ALT (SGPT) ≤ 2.5 institutional upper limit
- Creatinine clearance ≥ 60 ml/min
Willing and able to comply with the study prescriptions
No history of prior thoracic radiotherapy
No severe chronic obstructive pulmonary disease with hypoxemia or in the opinion of the investigator any physiological state leading to hypoxemia
Women should not be pregnant or lactating
No known infection with HIV, hepatitis B or C or any other active infection
Normal ECG with careful evaluation of QT/QTc
Have given written informed consent before patient registration

Exclusion criteria

Exclusion Criteria:

Recent (\< 3 months) severe cardiac disease (arrhythmia, congestive heart failure, infarction)
Patients with difficult peripheral intravenous access
History of prior thoracic radiotherapy
severe chronic obstructive pulmonary disease with hypoxemia or in the opinion of the investigator any physiological state leading to hypoxemia
Women who are pregnant or lactating
Known infection with HIV, hepatitis B or C or any other active infection

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 0 participants (actual)

Study arms

Other
treatment
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
Drug: TH-302 · Other: HX4 scan · Drug: Carboplatin · Drug: Paclitaxel · Radiation: Radiotherapy · Procedure: surgery

Interventions

DrugTH-302
TH-302 day 4 (pre-treatment) and weekly during chemo-radiotherapy (CRT)
OtherHX4 scan
HX 4 scan day 1 and day 8
DrugCarboplatin
2mg/ml/min
DrugPaclitaxel
50 mg/m2
RadiationRadiotherapy
23 x 1.8 Gy
Proceduresurgery
minimally invasive transhiatal approach including a one-field node dissection or transthoracic approach with a two-field lymph node dissection

What researchers measure

Primary outcomes

Dose Limiting Toxicity (DLT )
To determine the DLT and define the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
Time frame: within 30days postoperative

Secondary outcomes

hypoxia response in tumor
Presence of hypoxia response based on hypoxia imaging (HX4) at baseline and first administration of TH-302 (before chemoradiotherapy).
Time frame: day 4 and day 8
rate of pathological Complete Remission (pCR)
Presence of anti-tumor activity measured by the rate of pathological Complete Remission (pCR)
Time frame: within 30 days after surgery
histopathologic negative circumferential resection margin (CRM) rate
Presence of anti-tumor activity measured by histopathologic negative circumferential resection margin (CRM) rate.
Time frame: within 30 days after surgery
Local recurrence rate
Presence of anti-tumor activity measured by local recurrence rate
Time frame: within 30 days after surgery
distance recurrence rate
Presence of anti-tumor activity measured by distance recurrence rate
Time frame: within 30 days after surgery
Progression free survival
Presence of anti-tumor activity measured by progression free survival
Time frame: within 30 days after surgery
overall survival
Presence of anti-tumor activity measured by overall survival
Time frame: within 30 days after surgery
metabolic response
Presence of anti-tumor activity measured by metabolic response one month after treatment
Time frame: within 30 days after surgery

Study locations

No study locations are listed for this record.

References and documents

Publications

Larue RT, Van De Voorde L, Berbee M, van Elmpt WJ, Dubois LJ, Panth KM, Peeters SG, Claessens A, Schreurs WM, Nap M, Warmerdam FA, Erdkamp FL, Sosef MN, Lambin P. A phase 1 'window-of-opportunity' trial testing evofosfamide (TH-302), a tumour-selective hypoxia-activated cytotoxic prodrug, with preoperative chemoradiotherapy in oesophageal adenocarcinoma patients. BMC Cancer. 2016 Aug 17;16:644. doi: 10.1186/s12885-016-2709-z. PubMed 27535748 ↗

Individual participant data

Plan to share: Undecided

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 21, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02598687
Lead sponsor: Maastricht Radiation Oncology
Collaborators: Threshold Pharmaceuticals, Zuyderland Medical Centre
Responsible party: Sponsor
First posted: Nov 6, 2015
Start date: Dec 2015
Primary completion: Apr 2016
Completion: Apr 2016
Last update: Apr 21, 2016

Study contacts

Philippe Lambin, MD, PhD

principal investigator · MUMC+, dept Radiotherapy

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is withdrawn, as verified in Apr 2016. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: TH 302

Other studies in this condition

Esophageal Neoplasms →

Other studies from this sponsor

Maastricht Radiation Oncology →

Start the discussion