SEAL Study: Selinexor in Advanced Liposarcoma

  • Research type

    Research Study

  • Full title

    A PHASE 2-3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND STUDY OF SELINEXOR (KPT-330) VERSUS PLACEBO IN PATIENTS WITH ADVANCED UNRESECTABLE DEDIFFERENTIATED LIPOSARCOMA (DDLS)

  • IRAS ID

    206349

  • Contact name

    Robin Jones

  • Contact email

    robin.jones4@nhs.net

  • Sponsor organisation

    Karyopharm Therapeutics, Inc.

  • Eudract number

    2015-003594-14

  • Clinicaltrials.gov Identifier

    NCT02606461

  • Duration of Study in the UK

    1 years, 7 months, 2 days

  • Research summary

    Liposarcomas are cancers arising from fat cells and are amongst the most frequent type of soft tissue cancers, (frequently called soft tissue sarcoma). Liposarcomas account for approximately 15-20% of all soft tissue cancers. There are 3 well described types of fat cell cancers and among these is one called dedifferentiated liposarcoma (in short DDLS) and this tends to recur at sites where it was previously removed and is more likely to spread to other parts of the body such as the liver and lung. The initial treatment requires surgical removal of the cancer. However, as mentioned above it has a high tendency to come back. When it comes back drug treatment is frequently given and because there are not many effective treatments, disease of many patients does not respond well or comes back after a short period of treatment. For these reasons additional new treatments are being developed.
    Selinexor is an investigational product that has not yet been approved for marketing but has been tested in a variety of cancer types in many clinical trials and shown to stop the cancer of some patients from worsening including some patients with DDLS. Selinexor, works by trapping “tumor suppressing proteins” within the nucleus of the cells where they inherently work best to cause new cancer cells to die or stop growing.
    Selinexor (KPT 330) has been developed as a tablet which can be taken orally on 2 two days in a week. Selinexor has been given to more than 2500 patients in clinical trials with different cancers including over 100 patients with DDLS. This study will examine the effects of selinexor on the cancer and help gain more understanding of the safety profile.
    In this study, approximately 279 patients will be randomized, in a double-blind fashion to either selinexor or placebo treatment. Randomized means patients will be allocated at random (by chance alone) to receive one of the 2 study treatment options (selinexor or placebo). Double-blind means that neither patients nor the study doctor will know what treatment the patient has been assigned to, whether to selinexor or to placebo during the blinded part of the treatment. Patients on treatment will be closely monitored to assess disease control with CT or MRI scans every 6 weeks for the first 24 weeks and thereafter every 12 weeks. During these regular assessments, if the disease progresses (worsens) the treatment will be unblinded and patients on placebo will have the option to receive as open label the selinexor treatment. So that, all patients participating in the study in the end will have the option to receive selinexor if the treating physician consider it an appropriate option.
    The study is divided into phase 2 and phase 3. The phase 2 portion, in which the first 57 participating patients were randomized 1:1 (selinexor (N=27) to placebo (N=30) tablets) is now complete. The planned accrual of 222 patients to phase 3 portion, is ongoing and patients will be randomized in 2:1 (selinexor (N=138) to placebo (N=74)) meaning that patients have a 3 to 2 chance of receiving selinexor and not placebo in the blinded part.
    The study is expected to take approximately 27 months to complete. The primary endpoint analysis of progression free survival (PFS) will be performed approximately 12 months after enrolment of the last patient, once 209 PFS events are observed. At this point all patients will be unblinded and patients on placebo blinded treatment will be allowed to crossover to selinexor open label treatment if they and their treating physician so desire.
    All patients will be followed up for long-term survival, until the minimum required number death events are reached.

  • REC name

    South Central - Oxford B Research Ethics Committee

  • REC reference

    18/SC/0257

  • Date of REC Opinion

    3 Jul 2018

  • REC opinion

    Further Information Favourable Opinion