Clinical trial NCT03193437: Selinexor in Patients With Advanced Thymic Epithelial Tumor Progressing After Primary Chemotherapy
Official title: A Phase 2, Open-label Study of Selinexor (KPT-330) in Patients With Advanced Thymic Epithelial Tumor (TET) Progressing After Primary Chemotherapy (SELECT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Thymoma
Advanced Thymic Epithelial Tumor
Keywords: Thymus
Selinexor
KPT-330
Lead sponsor: Georgetown University
Sponsor class: OTHER
Collaborators: name: Hackensack Meridian Health
name: Karyopharm Therapeutics Inc
First posted: 2017-06-20
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability and effectiveness of selinexor in patients with advanced thymic epithelial tumor progressing after primary chemotherapy. This is a multicenter, open label phase II trial that uses a Simons two stage design. The study population is adults with histologically confirmed, advanced, inoperable TETs who are progressing after treatment with at least one platinum containing chemotherapy regimen.

This study is comprised of 2 similar phase II trials, one running in US (25 patients) and one running in EU (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


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed advanced TET (thymoma)
* Progression after Primary Chemotherapy
* No more than two previous lines (Neoadjuvant or chemoradiotherapy will count as one 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 five half lives 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; Hemoglobin \> 9.0 gm/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

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
* 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

Primary outcomes:
measure: Overall Response Rate
timeFrame: 24 months
Secondary outcomes:
measure: Overall Response Rate
timeFrame: 24 months
measure: 6 Month Progression Free Survival Rate
timeFrame: 6 months
measure: 24 Month Overall Survival Rate
timeFrame: 24 months
measure: Adverse Events
timeFrame: 24 months
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Hackensack
country: United States
facility: John Theurer Cancer Center - Hackensack University Medical Center
state: New Jersey
Study officials:
affiliation: Georgetown University
name: Chul Kim, MD
role: STUDY_CHAIR
References: