Squamous Cell Carcinoma
Conditions
Keywords
Squamous, SCC, Carcinoma, KPT-330, SINE, Selinexor, Karyopharm, Karyopharm Therapeutics, Lung, Head, Neck, Esophageal
Brief summary
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
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.
Interventions
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.
Sponsors
Karyopharm Therapeutics Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease Control Rate (DCR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | up to 14.6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the first administration of study drug up to 30 days follow-up (up to 14.6 months) | 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. |
| Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | From the first administration of study drug up to 30 days follow-up (up to 14.6 months) | 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. |
Countries
Canada, United States
Participant flow
Recruitment details
The study was conducted at 14 sites in United States and 1 site in Canada between 22 September 2014 and 10 December 2015.
Pre-assignment details
A total of 45 participants were enrolled and randomized.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Head and Neck-SCC Participants with advanced SCC of head and neck, 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. | 33 |
| Cohort 2: Lungs-SCC 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. | 4 |
| Cohort 3: Esophagus-SCC 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. | 1 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event (AE) | 1 | 0 | 0 |
| Overall Study | Death | 16 | 2 | 1 |
| Overall Study | Disease progression | 11 | 2 | 0 |
| Overall Study | Other | 5 | 0 | 0 |
| Overall Study | Participant discontinued study therapy | 2 | 0 | 0 |
| Overall Study | Participant withdrew informed consent | 2 | 1 | 2 |
Baseline characteristics
| Characteristic | Cohort 3: Esophagus-SCC | Total | Cohort 1: Head and Neck-SCC | Cohort 2: Lungs-SCC |
|---|---|---|---|---|
| Age, Continuous | 51.0 years | 59.1 years STANDARD_DEVIATION 9.91 | 58.5 years STANDARD_DEVIATION 10.05 | 66.3 years STANDARD_DEVIATION 6.34 |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other-unspecified | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 1 Participants | 35 Participants | 30 Participants | 4 Participants |
| Sex: Female, Male Female | 0 Participants | 4 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 34 Participants | 30 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 16 / 37 | 2 / 5 | 1 / 3 |
| other Total, other adverse events | 35 / 37 | 5 / 5 | 3 / 3 |
| serious Total, serious adverse events | 18 / 37 | 2 / 5 | 3 / 3 |
Outcome results
Primary
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.
Time frame: up to 14.6 months
Population: Analysis performed on mITT population that included all participants who received at least 1 dose of study drug, and had at least 1 post baseline efficacy assessment. Participants who discontinued prior to first post baseline efficacy assessment were included if discontinuation was due to disease progression, study drug related toxicity, or death.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Head and Neck-SCC | Percentage of Participants With Disease Control Rate (DCR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 21.2 percentage of participants |
| Cohort 2: Lungs-SCC | Percentage of Participants With Disease Control Rate (DCR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 0.0 percentage of participants |
| Cohort 3: Esophagus-SCC | Percentage of Participants With Disease Control Rate (DCR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 0.0 percentage of participants |
Secondary
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.
Time frame: From the first administration of study drug up to 30 days follow-up (up to 14.6 months)
Population: Analysis was performed on safety population that included all participants who had received any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Head and Neck-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Life Threatening (Grade 4) | 3 Participants |
| Cohort 1: Head and Neck-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Severe (Grade 3) | 21 Participants |
| Cohort 1: Head and Neck-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Mild (Grade 1) | 3 Participants |
| Cohort 1: Head and Neck-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Moderate (Grade 2) | 9 Participants |
| Cohort 1: Head and Neck-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Fatal (Grade 5) | 1 Participants |
| Cohort 2: Lungs-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Severe (Grade 3) | 4 Participants |
| Cohort 2: Lungs-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Mild (Grade 1) | 0 Participants |
| Cohort 2: Lungs-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Moderate (Grade 2) | 1 Participants |
| Cohort 2: Lungs-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Life Threatening (Grade 4) | 0 Participants |
| Cohort 2: Lungs-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Fatal (Grade 5) | 0 Participants |
| Cohort 3: Esophagus-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Fatal (Grade 5) | 0 Participants |
| Cohort 3: Esophagus-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Life Threatening (Grade 4) | 0 Participants |
| Cohort 3: Esophagus-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Mild (Grade 1) | 0 Participants |
| Cohort 3: Esophagus-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Severe (Grade 3) | 3 Participants |
| Cohort 3: Esophagus-SCC | Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale | Moderate (Grade 2) | 0 Participants |
Secondary
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.
Time frame: From the first administration of study drug up to 30 days follow-up (up to 14.6 months)
Population: Analysis was performed on safety population that included all participants who had received any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Head and Neck-SCC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 37 Participants |
| Cohort 1: Head and Neck-SCC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 18 Participants |
| Cohort 2: Lungs-SCC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 5 Participants |
| Cohort 2: Lungs-SCC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 2 Participants |
| Cohort 3: Esophagus-SCC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 3 Participants |
| Cohort 3: Esophagus-SCC | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 3 Participants |