Selinexor in Patients With Advanced Thymic Epithelial Tumor Progressing After Primary Chemotherapy

Phase 2

Terminated

• Conditions: Thymoma; Advanced Thymic Epithelial Tumor
• Interventions: Drug: Open Label Selinexor

• Registration Number: NCT03193437
• Lead Sponsor: Georgetown University

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-06-19
• Study First Submitted QC: 2017-06-19
• Study First Posted: 2017-06-20
• Study Start: 2018-04-03
• Primary Completion: 2020-07-27
• Study Completion: 2022-01-31
• Status Verified: 2022-04
• Results First Submitted: 2022-10-25
• Results First Submitted QC: 2023-02-10
• Last Update Submitted: 2023-02-10
• Results First Posted: 2023-02-16
• Last Update Posted: 2023-02-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Selinexor	Open Label Selinexor	Open Label Selinexor 40 mg

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	24 months	To determine the overall response rate per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+ PR.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate	24 months	To determine the overall response rate to according to modified ITMIG response criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT and MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
6 Month Progression Free Survival Rate	6 months	To determine six months progression free survival of patients with TET treated with selinexor
24 Month Overall Survival Rate	24 months	To determine overall 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

Trial Locations

Locations (2)

John Theurer Cancer Center - Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Georgetown Lombardi Comprehensive Cancer Center; 🇺🇸 Washington, District of Columbia, United States