Advanced Thymic Epithelial Tumour, Thymoma
Conditions
Brief summary
The aim of the study is 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. The study is an international, multicenter, open label phase II trial using Simons two stage design. The study population is adults with histologically confirmed, advanced, inoperable TETs who are progressing after treatment with least one platinum containing chemotherapy regimen. This study is comprised of 2 similar phase II tirals, one running in EU (25 patients) and one running in US (25 patients). There are two study arms: Arm A: Thymoma * Stage 1: 15 patients * Stage 2: 10 patients Arm B: Thymic carcinoma * Stage 1: 15 patients * Stage 2: 10 patients
Detailed description
Not provided
Interventions
DRUGSelinexor
Selinexor 60 mg oral tablets will be administered twice weekly, either Monday/Wednesday or on Tuesday/Thursday or on Wednesday/Friday in a 3-weeks-on and 1-week-off Schedule.
Sponsors
Institut Curie
Gustave Roussy, Cancer Campus, Grand Paris
Hospices Civils de Lyon
GSO Global Clinical Research BV
Karyopharm Therapeutics Inc
Morten Mau-Soerensen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed advanced TET (thymoma or thymic carcinoma) * Inoperable per local Investigator (Masaoka Stage III or IV) * Progression after treatment with least one platinum containing chemotherapyregimen * 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 interval from any investigational agents or cytotoxic chemotherapy to start of study is required * 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 * 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 3 months after participation in this study
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 24 months | To determine the overall response rate according to RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 6 months | To determine six months progression free survival of patients with TET treated with selinexor |
| Adverse Events | 24 months | The number of adverse events as determined by Common Terminology Criteria for Adverse Events (CTCAEs) version 4.03 |
Countries
Denmark, France
Contacts
Primary ContactMorten Mau-Soerensen, MD, PhD
Backup ContactKristoffer S Rohrberg, MD, PhD
Outcome results
None listed