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Esophageal CancerPhase 1NCT02598687

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

A Phase 1 study testing TH-302, HX4 scan and Carboplatin in people with Esophageal Cancer, run by Maastricht Radiation Oncology.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Esophageal Cancer
What is being tested?
TH-302, HX4 scan and Carboplatin
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Dec 2015to Apr 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 23Show fewer
  • 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

Who cannot join

  • 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

About this study

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

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.

Being tested
TH-302, HX4 scan, Carboplatin, Paclitaxel, Radiotherapy
Medical subject headings
Esophageal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TH-302Drug

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

  • HX4 scanOther

    HX 4 scan day 1 and day 8

  • CarboplatinDrug

    2mg/ml/min

  • PaclitaxelDrug

    50 mg/m2

  • RadiotherapyRadiation

    23 x 1.8 Gy

  • surgeryProcedure or surgery

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

Study groups in NCT02598687
Study groupRoleWhat they receive
treatmentOthertreatment 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
Receives: Drug: TH-302; Other: HX4 scan; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiotherapy; Procedure: surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicity (DLT )

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

    Measured: within 30days postoperative

Secondary outcomes (8)

  1. hypoxia response in tumor

    Presence of hypoxia response based on hypoxia imaging (HX4) at baseline and first administration of TH-302 (before chemoradiotherapy).

    Measured: day 4 and day 8

  2. rate of pathological Complete Remission (pCR)

    Presence of anti-tumor activity measured by the rate of pathological Complete Remission (pCR)

    Measured: within 30 days after surgery

  3. histopathologic negative circumferential resection margin (CRM) rate

    Presence of anti-tumor activity measured by histopathologic negative circumferential resection margin (CRM) rate.

    Measured: within 30 days after surgery

  4. Local recurrence rate

    Presence of anti-tumor activity measured by local recurrence rate

    Measured: within 30 days after surgery

  5. distance recurrence rate

    Presence of anti-tumor activity measured by distance recurrence rate

    Measured: within 30 days after surgery

  6. Progression free survival

    Presence of anti-tumor activity measured by progression free survival

    Measured: within 30 days after surgery

  7. overall survival

    Presence of anti-tumor activity measured by overall survival

    Measured: within 30 days after surgery

  8. metabolic response

    Presence of anti-tumor activity measured by metabolic response one month after treatment

    Measured: within 30 days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2015 (estimated)
  2. Study startDec 2015
  3. Primary completionApr 2016
  4. Study completionApr 2016

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

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02598687
Sponsor's protocol ID
14-27-03/09
Status last verified
Apr 2016
First submitted
29 May 2015
Last updated
21 Apr 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TH-302, HX4 scan and Carboplatin in people with Esophageal Cancer, run by Maastricht Radiation Oncology.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 21 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity (DLT ) (time frame: within 30days postoperative). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02598687, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2016.

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