Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
platinum pre-treated recurrent or metastatic, Head and neck squamous cell carcinoma, recurrent, metastatic, BKM120
Brief summary
Phase II Study of efficacy and safety of buparlisib (BKM120) plus paclitaxel versus placebo plus paclitaxel in recurrent or metastatic Head and Neck cancer previously pre-treated with a platinum therapy.The primary endpoint was PFS and the key secondary endpoint was Overall Survival.
Interventions
DRUGBuparlisib
Buparlisib comes in gelatin capsules and is taken orally at a dose of 100 mg/day.
Buparlisib matching placebo comes in gelatin capsules and is taken orally at a dose of 100 mg/day.
DRUGPaclitaxel
Paclitaxel is an intravenous infusion that is given once every week in 80 mg/m\^2.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has histologically/cytologically-confirmed HNSCC. * Patient has archival or fresh tumor tissue for the analysis of PI3K-related biomarkers. One tumor block (preferred) or a minimum of 12 unstained slides to be provided. Enrollment in the study is contingent on confirmation of an adequate amount of tumor tissue. * Patients with recurrent or metastatic disease resistant to platinum-based chemotherapy (defined as progression while on platinum-based chemotherapy given in the recurrent/metastatic setting). Pretreatment with cetuximab is allowed * Measurable disease as determined by per RECIST criteria v1.1. If the only site of measurable disease is a previously irradiated lesion, documented progression of disease and a 4 week period since radiotherapy completion is required * Adequate bone marrow function and organ function * ECOG Performance Status ≤ 1
Exclusion criteria
* Patient has received previous treatment with any AKT, mTOR inhibitors or PI3K pathway inhibitors; * Patient treated with more than one prior chemotherapy regimen for recurrent/metastatic disease * Patient has symptomatic CNS metastases. Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ≥ 28 days prior to the start of study treatment (including radiotherapy and/or surgery) and must have stable low dose of corticosteroid therapy; * Patient has not recovered to ≤ grade 1 (except alopecia) from related side effects of any prior antineoplastic therapy * Patient has any of the following cardiac abnormalities:symptomatic congestive heart failure, history of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy, Left Ventricular Ejection Fraction (LVEF) \<50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO); myocardial infarction ≤ 6 months prior to enrolment, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, symptomatic pericarditis, QTcF \> 480 msec on the screening ECG (using the QTcF formula);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Per Investigator Assessment | 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years | PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression per RECIST v. 1.1 or death due to any cause. If a patient has not progressed or died at the analysis cut-off date or when the patient receives further anti-neoplastic therapy, PFS was censored on the date of the last adequate tumor assessment before the earlier of the cut-off date or start of the further anti-neoplastic therapy date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) as Per Local Radiological Assessment | 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years | ORR: percentage of patients with best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1. CR is defined as disappearance of all target lesions and any pathological lymph nodes must have a short axis of \<10 mm and the disappearance of all non-target lesions). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm). |
| Time to Response (TTR) as Per Local Radiological Assessment | 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years | TTR is the time from date of randomization until first documented response (CR or PR, which has to be confirmed subsequently) according to RECIST v1.1. CR is defined as disappearance of all target lesions and any pathological lymph nodes must have a short axis of \<10 mm and the disappearance of all non-target lesions). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm). |
| Disease Control Rate (DCR) as Per Local Radiological Assessment | 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years | DCR is the percentage of patients with a best overall response of CR, PR or stable disease (SD), according to RECIST v1.1. CR is defined as disappearance of all target lesions & any pathological lymph nodes must have a short axis of \<10 mm & the disappearance of all non-target lesions). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm). SD is defined as neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm\^2. |
| Duration of Response (DoR) as Per Local Investigator | 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years | DoR is the time from the date of the first documented response (CR or PR, which had to be confirmed subsequently) to the date of the first radiologically documented disease progression or death due to disease according to RECIST v1.1 . |
| Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 | Baseline, every 6 weeks starting from cycle 2 day 15 up to 3.5 years | A summary of EORTC-QLQ-C30 scores by time window. Time to deterioration is the number of days between the date of randomization and the date of the assessment at which definitive deterioration is seen. Definitive Deterioration in global health status and symptoms was defined as a decrease in the subscale score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study. If a patient had not had an event prior to analysis cut-off or start of another anticancer therapy, time to deterioration was censored at the date of the last quality of life (QoL) evaluation. |
| Overall Survival (OS) | 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years | Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last contact. |
| Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for AUC0-24 and AUClast | Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15 | To Characterize PK of buparlisib given in combination with paclitaxel for AUC0-24 (area under plasma concentration-time curve from time 0 to end of dosing interval of 24 hours) & AUClast (AUC from time 0 to last measurable concentration sampling time). |
| Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Cmax | Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15 | To characterize the pharmacokinetics of buparlisib given in combination with paclitaxel for Cmax. |
| Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Tmax | Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15 | To characterize the pharmacokinetics of buparlisib given in combination with paclitaxel for Tmax. |
| Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for CL/F | Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15 | To characterize the pharmacokinetics of buparlisib given in combination with paclitaxel for CL/F. |
| Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35 | Baseline, every 6 weeks starting from cycle 2 day 15 up to 3.5 years | A summary of EORTC-QLQ-HN35 scores by time window. Time to deterioration is the number of days between the date of randomization and the date of the assessment at which definitive deterioration is seen. Definitive Deterioration in global health status and symptoms was defined as an increase in the subscale score of at least 10% compared to baseline, with no later decrease above this threshold observed during the course of the study. If a patient had not had an event prior to analysis cut-off or start of another anticancer therapy, time to deterioration was censored at the date of the last quality of life (QoL) evaluation. |
Countries
Australia, Canada, France, Germany, Hungary, India, Ireland, Italy, Japan, Poland, Russia, South Korea, Spain, Switzerland, Taiwan, Thailand, United Kingdom, United States
Participant flow
Recruitment details
Planned: 150; Analyzed: 158. Patients were randomized to receive treatment with buparlisib 100 mg daily (n=79) or placebo (n=79) in combination with paclitaxel.
Pre-assignment details
158 patients randomized in a 1:1 ratio to treatment with buparlisib plus paclitaxel or placebo plus paclitaxel; stratification: number of prior lines of treatment in the recurrent/metastatic setting (1 vs.2) & region of Investigator site (North America vs. Rest of the World). In this study, Not Completed = Discontinued study treatment per Protocol
Participants by arm
| Arm | Count |
|---|---|
| Buparlisib + Paclitaxel Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m\^2 weekly. | 79 |
| Buparlisib Matching Placebo + Paclitaxel Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m\^2 weekly. | 79 |
| Total | 158 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 11 |
| Overall Study | Death | 9 | 8 |
| Overall Study | Non-compliance with study treatment | 1 | 0 |
| Overall Study | Patient/guardian decision | 8 | 4 |
| Overall Study | Physician Decision | 6 | 2 |
| Overall Study | Progressive disease | 42 | 52 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Study terminated by Sponsor | 0 | 1 |
| Overall Study | Untreated - did not receive study drug | 3 | 1 |
Baseline characteristics
| Characteristic | Buparlisib + Paclitaxel | Buparlisib Matching Placebo + Paclitaxel | Total |
|---|---|---|---|
| Age, Continuous | 58.0 Years STANDARD_DEVIATION 9.44 | 58.2 Years STANDARD_DEVIATION 9.44 | 58.1 Years STANDARD_DEVIATION 9.41 |
| Race/Ethnicity, Customized East Asian | 12 Participants | 9 Participants | 21 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Mixed ethnicity | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Not reported | 13 Participants | 10 Participants | 23 Participants |
| Race/Ethnicity, Customized Other | 30 Participants | 34 Participants | 64 Participants |
| Race/Ethnicity, Customized Russian | 7 Participants | 4 Participants | 11 Participants |
| Race/Ethnicity, Customized South Asian | 6 Participants | 5 Participants | 11 Participants |
| Race/Ethnicity, Customized Southeast Asian | 4 Participants | 9 Participants | 13 Participants |
| Race/Ethnicity, Customized Unknown | 3 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Female | 14 Participants | 11 Participants | 25 Participants |
| Sex: Female, Male Male | 65 Participants | 68 Participants | 133 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 76 | 17 / 78 |
| other Total, other adverse events | 76 / 76 | 75 / 78 |
| serious Total, serious adverse events | 43 / 76 | 37 / 78 |
Outcome results
Primary
Progression Free Survival (PFS) Per Investigator Assessment
PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression per RECIST v. 1.1 or death due to any cause. If a patient has not progressed or died at the analysis cut-off date or when the patient receives further anti-neoplastic therapy, PFS was censored on the date of the last adequate tumor assessment before the earlier of the cut-off date or start of the further anti-neoplastic therapy date.
Time frame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
Population: The Full analysis set (FAS) includes all patients who were randomized to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Buparlisib + Paclitaxel | Progression Free Survival (PFS) Per Investigator Assessment | 4.63 months |
| Buparlisib Matching Placebo + Paclitaxel | Progression Free Survival (PFS) Per Investigator Assessment | 3.45 months |
95% CI: [0.44, 0.94]
Secondary
Disease Control Rate (DCR) as Per Local Radiological Assessment
DCR is the percentage of patients with a best overall response of CR, PR or stable disease (SD), according to RECIST v1.1. CR is defined as disappearance of all target lesions & any pathological lymph nodes must have a short axis of \<10 mm & the disappearance of all non-target lesions). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm). SD is defined as neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm\^2.
Time frame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
Population: The Full analysis set (FAS) includes all patients who were randomized to study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buparlisib + Paclitaxel | Disease Control Rate (DCR) as Per Local Radiological Assessment | 72.2 Percentage of participants |
| Buparlisib Matching Placebo + Paclitaxel | Disease Control Rate (DCR) as Per Local Radiological Assessment | 69.6 Percentage of participants |
Secondary
Duration of Response (DoR) as Per Local Investigator
DoR is the time from the date of the first documented response (CR or PR, which had to be confirmed subsequently) to the date of the first radiologically documented disease progression or death due to disease according to RECIST v1.1 .
Time frame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
Population: The Full analysis set (FAS) includes all patients who were randomized to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Buparlisib + Paclitaxel | Duration of Response (DoR) as Per Local Investigator | 3.06 months |
| Buparlisib Matching Placebo + Paclitaxel | Duration of Response (DoR) as Per Local Investigator | 4.17 months |
Secondary
Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30
A summary of EORTC-QLQ-C30 scores by time window. Time to deterioration is the number of days between the date of randomization and the date of the assessment at which definitive deterioration is seen. Definitive Deterioration in global health status and symptoms was defined as a decrease in the subscale score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study. If a patient had not had an event prior to analysis cut-off or start of another anticancer therapy, time to deterioration was censored at the date of the last quality of life (QoL) evaluation.
Time frame: Baseline, every 6 weeks starting from cycle 2 day 15 up to 3.5 years
Population: The Full analysis set (FAS) includes all patients who were randomized to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Buparlisib + Paclitaxel | Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 | 3.0 months |
| Buparlisib Matching Placebo + Paclitaxel | Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 | 3.5 months |
Secondary
Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35
A summary of EORTC-QLQ-HN35 scores by time window. Time to deterioration is the number of days between the date of randomization and the date of the assessment at which definitive deterioration is seen. Definitive Deterioration in global health status and symptoms was defined as an increase in the subscale score of at least 10% compared to baseline, with no later decrease above this threshold observed during the course of the study. If a patient had not had an event prior to analysis cut-off or start of another anticancer therapy, time to deterioration was censored at the date of the last quality of life (QoL) evaluation.
Time frame: Baseline, every 6 weeks starting from cycle 2 day 15 up to 3.5 years
Population: The Full analysis set (FAS) includes all patients who were randomized to study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Buparlisib + Paclitaxel | Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35 | Pain Subscale | 5.8 Months |
| Buparlisib + Paclitaxel | Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35 | Speech problems | 5.6 Months |
| Buparlisib + Paclitaxel | Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35 | Swallowing | 5.1 Months |
| Buparlisib + Paclitaxel | Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35 | Sense Problems | 5.1 Months |
| Buparlisib Matching Placebo + Paclitaxel | Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35 | Sense Problems | 4.6 Months |
| Buparlisib Matching Placebo + Paclitaxel | Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35 | Pain Subscale | 5.3 Months |
| Buparlisib Matching Placebo + Paclitaxel | Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35 | Swallowing | 4.6 Months |
| Buparlisib Matching Placebo + Paclitaxel | Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35 | Speech problems | 4.2 Months |
Secondary
Overall Response Rate (ORR) as Per Local Radiological Assessment
ORR: percentage of patients with best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1. CR is defined as disappearance of all target lesions and any pathological lymph nodes must have a short axis of \<10 mm and the disappearance of all non-target lesions). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm).
Time frame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
Population: The Full analysis set (FAS) includes all patients who were randomized to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Buparlisib + Paclitaxel | Overall Response Rate (ORR) as Per Local Radiological Assessment | 39.2 Percentage of participants |
| Buparlisib Matching Placebo + Paclitaxel | Overall Response Rate (ORR) as Per Local Radiological Assessment | 13.9 Percentage of participants |
Secondary
Overall Survival (OS)
Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last contact.
Time frame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
Population: The Full analysis set (FAS) includes all patients who were randomized to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Buparlisib + Paclitaxel | Overall Survival (OS) | 10.41 months |
| Buparlisib Matching Placebo + Paclitaxel | Overall Survival (OS) | 6.54 months |
95% CI: [0.49, 1.04]
Secondary
Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for AUC0-24 and AUClast
To Characterize PK of buparlisib given in combination with paclitaxel for AUC0-24 (area under plasma concentration-time curve from time 0 to end of dosing interval of 24 hours) & AUClast (AUC from time 0 to last measurable concentration sampling time).
Time frame: Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15
Population: Full Sampling Pharmacokinetic Analysis Set (FPAS): All pts in PAS who received planned dose of buparlisib every day for last consecutive 7 days before full PK profile assessment on C1D15, didn't vomit within 4 hours of buparlisib dosing, had at least 1 dose of paclitaxel before collection of PK sample for PK profile \& had evaluable full PK profile
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Buparlisib + Paclitaxel | Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for AUC0-24 and AUClast | AUC0-24 (n = 4) | 25628.56 ng*hr/mL |
| Buparlisib + Paclitaxel | Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for AUC0-24 and AUClast | AUClast (n = 4) | 25734.33 ng*hr/mL |
Secondary
Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for CL/F
To characterize the pharmacokinetics of buparlisib given in combination with paclitaxel for CL/F.
Time frame: Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15
Population: Full Sampling Pharmacokinetic Analysis Set (FPAS): All pts in PAS who received planned dose of buparlisib every day for last consecutive 7 days before full PK profile assessment on C1D15, didn't vomit within 4 hours of buparlisib dosing, had at least 1 dose of paclitaxel before collection of PK sample for PK profile \& had evaluable full PK profile
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Buparlisib + Paclitaxel | Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for CL/F | 4.14 L/hr |
Secondary
Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Cmax
To characterize the pharmacokinetics of buparlisib given in combination with paclitaxel for Cmax.
Time frame: Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15
Population: Full Sampling Pharmacokinetic Analysis Set (FPAS): All pts in PAS who received planned dose of buparlisib every day for last consecutive 7 days before full PK profile assessment on C1D15, didn't vomit within 4 hours of buparlisib dosing, had at least 1 dose of paclitaxel before collection of PK sample for PK profile \& had evaluable full PK profile
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Buparlisib + Paclitaxel | Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Cmax | 1775.00 ng/mL |
Secondary
Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Tmax
To characterize the pharmacokinetics of buparlisib given in combination with paclitaxel for Tmax.
Time frame: Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15
Population: Full Sampling Pharmacokinetic Analysis Set (FPAS): All pts in PAS who received planned dose of buparlisib every day for last consecutive 7 days before full PK profile assessment on C1D15, didn't vomit within 4 hours of buparlisib dosing, had at least 1 dose of paclitaxel before collection of PK sample for PK profile \& had evaluable full PK profile
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Buparlisib + Paclitaxel | Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Tmax | 2.42 hour (hr) |
Secondary
Time to Response (TTR) as Per Local Radiological Assessment
TTR is the time from date of randomization until first documented response (CR or PR, which has to be confirmed subsequently) according to RECIST v1.1. CR is defined as disappearance of all target lesions and any pathological lymph nodes must have a short axis of \<10 mm and the disappearance of all non-target lesions). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm).
Time frame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
Population: The Full analysis set (FAS) includes all patients who were randomized to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Buparlisib + Paclitaxel | Time to Response (TTR) as Per Local Radiological Assessment | 1.02 months |
| Buparlisib Matching Placebo + Paclitaxel | Time to Response (TTR) as Per Local Radiological Assessment | 0.99 months |