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

Phase 2TerminatedNCT01852292

Novartis Pharmaceuticals157 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

157

Conditions

Head and Neck Squamous Cell Carcinoma

Interventions

BuparlisibDRUG

Buparlisib comes in gelatin capsules and is taken orally at a dose of 100 mg/day.

Buparlisib matching PlaceboDRUG

Buparlisib matching placebo comes in gelatin capsules and is taken orally at a dose of 100 mg/day.

PaclitaxelDRUG

Paclitaxel is an intravenous infusion that is given once every week in 80 mg/m\^2.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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);

Locations (58)

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

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

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).

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Highlands Oncology Group

Fayetteville, Arkansas, United States

Dana Farber Cancer Institute IRB

Boston, Massachusetts, United States

Washington U School of Medicine Center for Clinical Studies SC - BKM120H2201

St Louis, Missouri, United States

The Mount Sinai Hospital Dept of Oncology

New York, New York, United States

University of N.C. at Chapel Hill Lineberger Comp. Cancer Ctr.

Chapel Hill, North Carolina, United States

University Hospitals Case Medical Center Univ. Hospitals of Cleveland

Cleveland, Ohio, United States

UPMC Cancer Centers BKM120H2201

Pittsburgh, Pennsylvania, United States

Novartis Investigative Site

St Leonards, New South Wales, Australia

Novartis Investigative Site

Hamilton, Ontario, Canada

Novartis Investigative Site

Montreal, Quebec, Canada

...and 48 more locations

Time frame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

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

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

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

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

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

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

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

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