E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced thymic epithelial tumour (TET) progressing after primary chemotherapy |
|
E.1.1.1 | Medical condition in easily understood language |
advanced Thymoma and Thymic carcinoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055108 |
E.1.2 | Term | Thymic cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043670 |
E.1.2 | Term | Thymoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043674 |
E.1.2 | Term | Thymoma malignant recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061031 |
E.1.2 | Term | Thymoma malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To determine the efficacy of selinexor in adults with TETs determined by overall response rate (RECIST 1.1) in two parallel cohorts of patients with advanced thymomas or thymic carcinomas |
|
E.2.2 | Secondary objectives of the trial |
• To determine the efficacy of Selinexor in adults with TETs determined by overall response rate according to modified ITMIG response criteria
• To determine the overall response rate of selinexor in patients with advanced thymic carcinoma with squamous cell histology
• To determine six months PFS of patients with TET treated with selinexor
• To determine overall survival of patients with TET treated with selinexor
• To evaluate exploratory biomarkers for prediction of response to selinexor in patients with TET
• To determine progression free survival in patients with advanced, inoperable TETs treated with selinexor
• To evaluate safety and tolerability of Selinexor |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Histologically confirmed advanced TET (thymoma or thymic carcinoma)
-Progression after primary chemotherapy
-Not more than 2 previous lines (neoadj or chemoradiotherapy will count as 1 line if disease progression has occurred within 6 months.
-Inoperable per local Investigator (Masaoka Stage III or IV)
-Progression after treatment with least one platinum containing chemotherapy regimen
-Measurable disease (RECIST 1.1)
-Age ≥18 years
-ECOG PS <2
-Patients must have recovered from the toxic effects of prior therapy at the time of initiation of the study drug unless toxicity is stable.
-A 4 weeks or 5 half lifes interval from any investigational agents or cytotoxic chemotherapy to start of study is required (whichever is shorter)
-Signed informed consent
-Adequate bone marrow function and organ function:
-Hematopoietic function: total white blood cell count (WBC) ≥ 3000/mm³, absolute neutrophil count (ANC) ≥ 1500/mm³, platelet count ≥ 100,000/mm², circulating lymphocytes < 50,000/mm³, Haemoglobin >=9.0mmol/dL
-Hepatic function: bilirubin < 1.5 times the upper limit of normal (ULN), ALT < 2.5 times ULN or ALT < 5.0 times ULN in the presence of liver metastases
-Creatinine clearance > 30 ml/min according to Cockcroft-Gault
-Patients of childbearing potential must agree to use adequate birth control during and for 7 months after participation in this study |
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E.4 | Principal exclusion criteria |
• No significant medical illness that in the investigator’s opinion cannot be adequately controlled with appropriate therapy or would compromise the patient’s ability to tolerate this therapy, including
- Unstable cardiovascular function
- Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen)
- Markedly decreased visual acuity
- Active infection requiring intravenous antibiotics
• Pregnancy or breast-feeding
• Symptomatic brain metastasis requiring corticosteroids
• Uncontrolled autoimmune disorders. Patients with autoimmune disorders under control on medication may be included. Patients with pure red cell aplasia may be included if haemoglobin levels are relatively stable on transfusions or medication
• Any other cancer (excluding radically operated localised squamous skin cancer) with clinical activity within the last 2 years
• Significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral medications
• No dehydration of NCI-CTCAE grade ≥ 1
• Serious psychiatric or medical conditions that could interfere with treatment.
• No history of organ allograft
• No concurrent therapy with approved or investigational anticancer therapeutics
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate according to RECIST 1.1 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessment of disease status every 8 weeks from start of therapy within study |
|
E.5.2 | Secondary end point(s) |
1 Overall response rate according to modified ITMIG response criteria
2 Six months PFS
3 Overall survival
4 Common Terminology Criteria for Adverse Events (CTCAEs) version 4.03
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.Assessment of disease status every 8 weeks from start of therapy within study
2 Six months after start of treatment within the study
3 At the time of death of patient
4 From start of therapy within study to End of treatent visit |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |