Selinexor Treatment of Advanced Relapsed/Refractory Squamous Cell Carcinomas

Study Overview
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Brief Summary
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Open-label, multi-center, single-arm, Phase 2 study of oral selinexor in patients with SCC of the head and neck (HN-SCC; Cohort 1), lung (L-SCC; Cohort 2), or esophagus (E-SCC; Cohort 3) who have relapsed or have metastasis following chemotherapy.

Detailed Description
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This is a multicenter, open-label, single-arm Phase 2 study of the SINE selinexor given orally to patients diagnosed with advanced SCC of the head and neck, lung, or esophagus who have experienced relapse and/or metastasis following multiple prior chemotherapy treatments (<2 lines of therapy). Patients will receive fixed doses of selinexor tablets twice weekly in 28-day cycles. Patients may continue from one cycle to the next without interruption as along as all criteria are met and no reason for discontinuation occurs.

Official Title
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A Phase 2, Open-Label Study of the Safety and Efficacy of the Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck, Lung, or Esophagus

Conditions
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Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Selinexor (KPT-330)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older confirmed SCC of the head and neck, lung, or esophagus 1 to 2 prior therapies measurable disease at screening and documented progression within the past 6 weeks Exclusion Criteria: patients requiring total parenteral nutrition unstable cardiovascular function substantially impaired gastrointestinal function Symptomatic brain metastases another malignancy within 3 years except adequately treated in situ carcinoma of any type, basal or non-melanomatous skin cancer

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Head and Neck-SCC<br>Participants with advanced squamous cell carcinoma (SCC) of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 milligram (mg) selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets less than [<] 100*10^9 per litre [/L]), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities. | Drug: Selinexor (KPT-330)<br>* Oral tablet or suspension at 60, 80, 100 or 120 mg per patient-specific body surface area category. Dosing will occur twice weekly in 28-days cycle.<br>* Other names: KPT-330;|
| Experimental: Cohort 2: Lungs-SCC<br>Participants with advanced SCC of lungs, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities. | Drug: Selinexor (KPT-330)<br>* Oral tablet or suspension at 60, 80, 100 or 120 mg per patient-specific body surface area category. Dosing will occur twice weekly in 28-days cycle.<br>* Other names: KPT-330;|
| Experimental: Cohort 3: Esophagus-SCC<br>Participants with advanced SCC of esophagus, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities. | Drug: Selinexor (KPT-330)<br>* Oral tablet or suspension at 60, 80, 100 or 120 mg per patient-specific body surface area category. Dosing will occur twice weekly in 28-days cycle.<br>* Other names: KPT-330;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Control Rate (DCR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | DCR was defined as the best overall response of complete response (CR), partial response (PR), or stable disease (SD). CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Participant response was evaluated by physical examinations and computed tomography (CT)/Magnetic Resonance Imaging (MRI) (or optional positron emission tomography [PET]/CT) and assessed by RECIST 1.1 criteria. | up to 14.6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An adverse event (AE) was defined as any unfavorable sign and unintended sign (including abnormal laboratory finding), symptom, or disease temporarily associated with the use of the study drug, whether or not related to study drug. An SAE was defined as any untoward medical occurrence that occurs at any dose (including after informed consent was signed and prior to dosing) that resulted in death, was life-threatening (participant was at immediate risk of death from event), required in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect, and important medical events. A TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after first dose of treatment through 30 days following last dose of study treatment, or any event considered drug-related by investigator through end of study. | From the first administration of study drug up to 30 days follow-up (up to 14.6 months) | 
| Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | AE:Any unfavorable sign and unintended sign,symptom, or disease temporarily associated with use of study drug, whether or not related to it. SAE:Any untoward medical occurrence that occurs at any dose (after informed consent was signed, prior dosing) that resulted in death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, and important medical events. TEAE:Any AE with onset or worsening of existing condition on or after first dose through 30 days following last dose of study drug, or any event considered drug-related by investigator through end of study. Severity(Grades 1 to 5) of each AE was categorized as either mild=1(transient,does not interfere with daily activities), moderate=2(low level of inconvenience or concern,interfere with daily activities), severe=3(interrupt usual daily activities), life threatening=4 or fatal=5, higher grade reported worst outcome. | From the first administration of study drug up to 30 days follow-up (up to 14.6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous, SCC, Carcinoma, KPT-330, SINE, Selinexor, Karyopharm, Karyopharm Therapeutics, Lung, Head, Neck, Esophageal