Study of addition of belinostat to chemotherapy before surgery in patients with Thymic Epithelial Tumors (TET)

• Register: EUCTR
• Last refreshed on: 12 February 2018
• Main ID: EUCTR2017-002561-21-FR
• Date of registration: 02/02/2018
• Prospective Registration: Yes
• Primary sponsor: IFCT
• Public title: Study of addition of belinostat to chemotherapy before surgery in patients with Thymic Epithelial Tumors (TET)
• Scientific title: Randomised Open Label Adaptive Phase III trial of addition of Belinostat to chemotherapy in patients with locally advanced potentially resectable Thymic Epithelial Tumors (TET) - BELCAP
• Date of first enrolment: 02/02/2018
• Target sample size: 100
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002561-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Adaptative; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Italy, Spain

Contacts

• Name: Contact
• Affiliation: IFCT

• Name: Contact
• Affiliation: IFCT

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically confirmed Thymoma (WHO classification A, AB, B1, B2, B3 ) or Thymic carcinoma.
The diagnosis of TET will be confirmed by a central expert tumour board based on the review of the tumor biopsy realized at site of the initial diagnosis; no new tumour biopsy is required for TET diagnosis.
2. Potentially resectable stage II-IVB (TNM IASLC-ITMIG 2014)
3. Age = 18 years
4. WHO performance index of 0, 1
5. Adequate organ function
6. No previous treatment for TET
7. Signed informed consent form


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion criteria:
1. History of cancer except cancer dating from over three years ago and considered to be cured; appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma and stage I uterine cancer.
2. History of previous radiotherapy to the mediastinum
3. History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to any of the study drugs or their excipients
4. Decompensated Myasthenia Gravis
5. Significant cardiovascular disease of congestive heart failure Class III/IV to the NYHA Functional Classification, myocardial infarction within the past 6 months, unstable angina and unstable arrhythmia, left ventricular ejection fraction (LVEF) < 50% by either cardiac ultrasound or cardiac scintigraphy
6. Baseline prolongation of QT/QTc interval > 480ms for 7 or more days; long QT syndrome;
7. Concomitant use of strong UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir, ketoconazole, sorafenib) and concomitant medication that may cause Torsade de Pointes (refer to appendix I for list of drugs with known risk);
8. Pregnant or breast-feeding women; Women of childbearing age and potential who are not willing to use effective contraception during the study treatment period and until 30 days after last dose of study drug. Male patients who have female partners of childbearing age and potential who are not willing to use effective contraception during the study treatment period and until 30 days after last dose of study drug.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Locally advanced potentially resectable Thymic Epithelial Tumors
MedDRA version: 20.0 Level: PT Classification code 10061031 Term: Thymoma malignant System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: PT Classification code 10026533 Term: Malignant neoplasm of thymus System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Beleodaq (in the USA)
Product Name: Belinostat
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: belinostat
CAS Number: 414864-00-9
Other descriptive name: PXD101
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Main Objective: To evaluate the efficacy of the induction treatment (after surgery and before any radiotherapy treatment) of adding belinostat to standard chemotherapy

Primary end point(s): % R0 Complete Resection in the two arms (experimental and control arms). R0 Complete Resection is defined as a complete resection of the primary tumor with no microscopic residual tumor (margins considered as microscopically negative: = 1 mm) and complete macroscopic resection of pleural implants in stage IVA disease, assessed by a blinded pathologic central review.

Timepoint(s) of evaluation of this end point: After surgery (6 weeks after the last treatment)

Secondary Objective: To evaluate the efficacy of the induction treatment (after surgery and before any radiotherapy treatment)
To evaluate the risk of relapse (local and/or regional relapse and/or distant metastasis) during the follow up period
To evaluate the long term overall survival
To evaluate overall tolerance
To evaluate quality of life

Secondary Outcome(s)

Secondary end point(s): % R0 Complete Resection assessed by the investigator’s site, with R0 defined as for the primary endpoint
% surgical resection of primary tumor defined as % of patients arriving to surgical resection after induction treatment
Pathological complete response (pCR) defined as % of patients with no microscopic residual tumor in the pathologic evaluation of the surgical specimen
Complete surgical resection by operative technique and boarding approach defined as % of R0 achieved by boarding approach (sternotomy-mediastinotomy-thoracothomy-videothoracoscopy-clamshell)
Objective Response Rate (ORR) defined as % of patients achieving a Response (complete response + partial response) after induction treatment according to RECIST 1.1 assessed by a Chest-CT Scan
DFS (Disease-Free Survival) defined as the time from the date of randomisation to the date of documented relapse or death of any cause. DFS will be estimated using the Kaplan-Meier method and plotted as curves by treatment group.
% Relapse defined as % of any relapse (local-regional-distant).
Pattern of relapse defined as % of relapse by anatomic sites and % of local versus regional versus distant relapse.
Post-operative morbidity and mortality defined as morbidity and mortality rate.
Other cancers defined as cancers other than TET.
To assess the impact of treatment toxicity until surgery by using QLQ-C30 LC13 and EQ-5D questionnaires.
To assess long term quality of life by using QLQ-C30 LC13 and EQ-5D questionnaires during the follow-up period

Timepoint(s) of evaluation of this end point: After surgery (6 weeks after the last treatment)
After surgery (6 weeks after the last treatment)
After surgery (6 weeks after the last treatment)
After surgery (6 weeks after the last treatment)
After surgery (6 weeks after the last treatment)
4 weeks after the last treatment and before surgery
3 years, 5 years and 10 year
3 years, 5 years and 10 year
3 years, 5 years and 10 year
3 months
3 months
Until the end of the 10-year follow-up period
14 days before inclusion, before each cycle of treatment (week 1, week 4 and week 7), and at end of treatment visit (week 121) and post-surgery visit (6 weeks after surgery +/- 1 week 24).

Secondary ID(s)

IFCT-1604

Source(s) of Monetary Support

Onxeo