NCT02598687

Brief 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.

Trial Health

15
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Dec 2015

Shorter than P25 for phase_1

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 29, 2015

Completed
5 months until next milestone

First Posted

Study publicly available on registry

November 6, 2015

Completed
25 days until next milestone

Study Start

First participant enrolled

December 1, 2015

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
Last Updated

April 21, 2016

Status Verified

April 1, 2016

Enrollment Period

4 months

First QC Date

May 29, 2015

Last Update Submit

April 20, 2016

Conditions

Esophageal Cancer

Outcome Measures

Primary Outcomes (1)

  • Dose Limiting Toxicity (DLT )

    To determine the DLT and define the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)

    within 30days postoperative

Secondary Outcomes (8)

  • hypoxia response in tumor

    day 4 and day 8

  • rate of pathological Complete Remission (pCR)

    within 30 days after surgery

  • histopathologic negative circumferential resection margin (CRM) rate

    within 30 days after surgery

  • Local recurrence rate

    within 30 days after surgery

  • distance recurrence rate

    within 30 days after surgery

  • +3 more secondary outcomes

Study Arms (1)

treatment

OTHER

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-302Other: HX4 scanDrug: CarboplatinDrug: PaclitaxelRadiation: RadiotherapyProcedure: surgery

Interventions

TH-302DRUG

TH-302 day 4 (pre-treatment) and weekly during chemo-radiotherapy (CRT)

treatment
HX4 scanOTHER

HX 4 scan day 1 and day 8

treatment
CarboplatinDRUG

2mg/ml/min

treatment
PaclitaxelDRUG

50 mg/m2

treatment
RadiotherapyRADIATION

23 x 1.8 Gy

treatment
surgeryPROCEDURE

minimally invasive transhiatal approach including a one-field node dissection or transthoracic approach with a two-field lymph node dissection

treatment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +8 more criteria

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • 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.

    PMID: 27535748DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

TH 302CarboplatinPaclitaxelRadiotherapySurgical Procedures, Operative

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic ChemicalsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsDiterpenesTerpenesTherapeutics

Study Officials

  • Philippe Lambin, MD, PhD

    MUMC+, dept Radiotherapy

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 29, 2015

First Posted

November 6, 2015

Study Start

December 1, 2015

Primary Completion

April 1, 2016

Study Completion

April 1, 2016

Last Updated

April 21, 2016

Record last verified: 2016-04