Clinical trial NCT01852292: 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
Official title: Double Blind, Placebo Controlled Study Assessing the Efficacy of Buparlisib (BKM120) Plus Paclitaxel Versus Placebo Plus Paclitaxel in Patients With Platinum Pre-treated Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: platinum pre-treated recurrent or metastatic
Head and neck squamous cell carcinoma
recurrent
metastatic
BKM120
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-05-13
Enrollment: 157
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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);

Primary outcomes:
measure: Progression Free Survival (PFS) Per Investigator Assessment
timeFrame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
measure: Overall Response Rate (ORR) as Per Local Radiological Assessment
timeFrame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
measure: Time to Response (TTR) as Per Local Radiological Assessment
timeFrame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
measure: Disease Control Rate (DCR) as Per Local Radiological Assessment
timeFrame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
measure: Duration of Response (DoR) as Per Local Investigator
timeFrame: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
measure: Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30
timeFrame: Baseline, every 6 weeks starting from cycle 2 day 15 up to 3.5 years
measure: 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
timeFrame: Baseline, every 6 weeks starting from cycle 2 day 15 up to 3.5 years
measure: Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for AUC0-24 and AUClast
timeFrame: 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
measure: Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Cmax
timeFrame: 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
measure: Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Tmax
timeFrame: 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
measure: Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for CL/F
timeFrame: 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
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute IRB
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington U School of Medicine Center for Clinical Studies SC - BKM120H2201
state: Missouri
city: New York
country: United States
facility: The Mount Sinai Hospital Dept of Oncology
state: New York
city: Chapel Hill
country: United States
facility: University of N.C. at Chapel Hill Lineberger Comp. Cancer Ctr.
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center Univ. Hospitals of Cleveland
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers BKM120H2201
state: Pennsylvania
city: St Leonards
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Saint Herblain cedex
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Nyiregyhaza
country: Hungary
facility: Novartis Investigative Site
city: Nashik
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Dehli
country: India
facility: Novartis Investigative Site
state: New Delhi
city: Jaipur
country: India
facility: Novartis Investigative Site
state: Rajasthan
city: Kolkata
country: India
facility: Novartis Investigative Site
state: West Bengal
city: Kerala
country: India
facility: Novartis Investigative Site
city: Mumbai
country: India
facility: Novartis Investigative Site
city: Dublin 4
country: Ireland
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Palermo
country: Italy
facility: Novartis Investigative Site
state: PA
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Salerno
country: Italy
facility: Novartis Investigative Site
state: SA
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Venezia
country: Italy
facility: Novartis Investigative Site
state: VE
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Koto-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Minato-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho-gu
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Leningrad Region
country: Russian Federation
facility: Novartis Investigative Site
state: Russia
city: Nizhniy Novgorod
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: Genève
country: Switzerland
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
city: Kaohsiung City
country: Taiwan
facility: Novartis Investigative Site
city: Taichung City
country: Taiwan
facility: Novartis Investigative Site
city: Songkla
country: Thailand
facility: Novartis Investigative Site
state: Hat Yai
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
state: Scotland
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Soulieres D, Faivre S, Mesia R, Remenar E, Li SH, Karpenko A, Dechaphunkul A, Ochsenreither S, Kiss LA, Lin JC, Nagarkar R, Tamas L, Kim SB, Erfan J, Alyasova A, Kasper S, Barone C, Turri S, Chakravartty A, Chol M, Aimone P, Hirawat S, Licitra L. Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Oncol. 2017 Mar;18(3):323-335. doi: 10.1016/S1470-2045(17)30064-5. Epub 2017 Jan 26.