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

• ClinicalTrials.gov Identifier: NCT01852292
• Recruitment Status: Terminated
• First Posted: May 13, 2013
• Results First Posted: June 26, 2018
• Last Update Posted: July 24, 2018
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Head and Neck Squamous Cell Carcinoma
• Interventions: Drug: Buparlisib; Drug: Buparlisib matching Placebo; Drug: Paclitaxel
• Enrollment: 157

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

Arm/Group Title	Buparlisib + Weekly Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and weekly paclitaxel.	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and weekly paclitaxel.
Period Title: Overall Study
Started	79	79
Completed	0 [1]	0 [1]
Not Completed	79	79
Reason Not Completed
Untreated - did not receive study drug	3	1
Death	9	8
Patient/guardian decision	8	4
Adverse Event	8	11
Physician Decision	6	2
Protocol Violation	2	0
Non-compliance with study treatment	1	0
Study terminated by Sponsor	0	1
Progressive disease	42	52
[1] Completed = participants who were ongoing and did not discontinue study treatment per protocol

Baseline Characteristics

Arm/Group Title		Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel	Total
Arm/Group Description		Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	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.	Total of all reporting groups
Overall Number of Baseline Participants		79	79	158
Baseline Analysis Population Description		The Full analysis set (FAS) includes all patients who were randomized to study treatment.
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	79 participants	79 participants	158 participants
		58.0 (9.44)	58.2 (9.44)	58.1 (9.41)
		[1] Measure Analysis Population Description: The Full analysis set (FAS) includes all patients who were randomized to study treatment.
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	79 participants	79 participants	158 participants
	Female	14 17.7%	11 13.9%	25 15.8%
	Male	65 82.3%	68 86.1%	133 84.2%
		[1] Measure Analysis Population Description: The Full analysis set (FAS) includes all patients who were randomized to study treatment.
Race/Ethnicity, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	79 participants	79 participants	158 participants
Hispanic or Latino		3 3.8%	0 0.0%	3 1.9%
East Asian		12 15.2%	9 11.4%	21 13.3%
Southeast Asian		4 5.1%	9 11.4%	13 8.2%
South Asian		6 7.6%	5 6.3%	11 7.0%
Russian		7 8.9%	4 5.1%	11 7.0%
Mixed ethnicity		1 1.3%	2 2.5%	3 1.9%
Not reported		13 16.5%	10 12.7%	23 14.6%
Unknown		3 3.8%	6 7.6%	9 5.7%
Other		30 38.0%	34 43.0%	64 40.5%
		[1] Measure Analysis Population Description: The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Per Investigator Assessment
Description	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

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description:	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	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.
Overall Number of Participants Analyzed	79	79
Median (95% Confidence Interval); Unit of Measure: months
	4.63; (3.52 to 5.32)	3.45; (2.17 to 3.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Buparlisib + Paclitaxel, Buparlisib Matching Placebo + Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Double Criteria for PFS
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.646
	Confidence Interval	(2-Sided) 95%; 0.44 to 0.94
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Survival (OS)
Description	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

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description:	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	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.
Overall Number of Participants Analyzed	79	79
Median (95% Confidence Interval); Unit of Measure: months
	10.41; (7.29 to 12.78)	6.54; (5.26 to 8.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Buparlisib + Paclitaxel, Buparlisib Matching Placebo + Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Double criteria for OS
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.49 to 1.04
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Response Rate (ORR) as Per Local Radiological Assessment
Description	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

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description:	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	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.
Overall Number of Participants Analyzed	79	79
Median (95% Confidence Interval); Unit of Measure: Percentage of participants
	39.2; (28.4 to 50.9)	13.9; (7.2 to 23.5)

4. Secondary Outcome

Title	Time to Response (TTR) as Per Local Radiological Assessment
Description	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

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description:	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	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.
Overall Number of Participants Analyzed	79	79
Median (Full Range); Unit of Measure: months
	1.02; (0.8 to 9.2)	0.99; (0.8 to 5.1)

5. Secondary Outcome

Title	Disease Control Rate (DCR) as Per Local Radiological Assessment
Description	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

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description:	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	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.
Overall Number of Participants Analyzed	79	79
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	72.2; (60.9 to 81.7)	69.6; (58.2 to 79.5)

6. Secondary Outcome

Title	Duration of Response (DoR) as Per Local Investigator
Description	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

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description:	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	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.
Overall Number of Participants Analyzed	79	79
Median (Full Range); Unit of Measure: months
	3.06; (2.1 to 9.6)	4.17; (2.7 to 5.6)

7. Secondary Outcome

Title	Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30
Description	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

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description:	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	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.
Overall Number of Participants Analyzed	79	79
Median (95% Confidence Interval); Unit of Measure: months
	3.0; (1.6 to 4.9)	3.5; (2.1 to 4.3)

8. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description:	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	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.
Overall Number of Participants Analyzed	79	79
Median (95% Confidence Interval); Unit of Measure: Months
Pain Subscale	5.8; (4.2 to 7.3)	5.3; (3.2 to 6.8)
Speech problems	5.6; (4.1 to 6.9)	4.2; (2.2 to 5.4)
Swallowing	5.1; (3.7 to 7.2)	4.6; (2.8 to 6.7)
Sense Problems	5.1; (3.1 to 7.3)	4.6; (2.9 to 6.5)

9. Secondary Outcome

Title	Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for AUC0-24 and AUClast
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title		Buparlisib + Paclitaxel
Arm/Group Description:		Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Overall Number of Participants Analyzed		79
Median (Full Range); Unit of Measure: ng*hr/mL
AUC0-24 (n = 4)	Number Analyzed	4 participants
		25628.56; (13651.75 to 33375.10)
AUClast (n = 4)	Number Analyzed	4 participants
		25734.33; (13651.75 to 33306.37)

10. Secondary Outcome

Title	Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Cmax
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Buparlisib + Paclitaxel
Arm/Group Description:	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Overall Number of Participants Analyzed	79
Median (Full Range); Unit of Measure: ng/mL
	1775.00; (834.00 to 2180.00)

11. Secondary Outcome

Title	Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Tmax
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Buparlisib + Paclitaxel
Arm/Group Description:	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Overall Number of Participants Analyzed	79
Median (Full Range); Unit of Measure: hour (hr)
	2.42; (1.00 to 4.00)

12. Secondary Outcome

Title	Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for CL/F
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Buparlisib + Paclitaxel
Arm/Group Description:	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Overall Number of Participants Analyzed	79
Median (Full Range); Unit of Measure: L/hr
	4.14; (3.00 to 7.33)

Adverse Events

Time Frame	Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3.5 years.
Adverse Event Reporting Description	AEs, SAEs based on Safety Set: all pts who received at least 1 dose of study trtmnt & had at least 1 post-baseline safety assessment. Pts analyzed according to study trtmnt actually received, defined as trtmnt pt received on 1st day of study trtmnt
Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	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.
All-Cause Mortality
	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	16/76 (21.05%)	17/78 (21.79%)
Serious Adverse Events
	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	43/76 (56.58%)	37/78 (47.44%)
Blood and lymphatic system disorders
Anaemia † 1	3/76 (3.95%)	3/78 (3.85%)
Febrile neutropenia † 1	1/76 (1.32%)	1/78 (1.28%)
Leukopenia † 1	1/76 (1.32%)	0/78 (0.00%)
Neutropenia † 1	2/76 (2.63%)	0/78 (0.00%)
Thrombocytopenia † 1	1/76 (1.32%)	0/78 (0.00%)
Cardiac disorders
Cardiac arrest † 1	1/76 (1.32%)	1/78 (1.28%)
Sinus bradycardia † 1	0/76 (0.00%)	1/78 (1.28%)
Endocrine disorders
Hypercalcaemia of malignancy † 1	0/76 (0.00%)	1/78 (1.28%)
Eye disorders
Blindness † 1	0/76 (0.00%)	1/78 (1.28%)
Gastrointestinal disorders
Abdominal pain † 1	2/76 (2.63%)	1/78 (1.28%)
Aorto-oesophageal fistula † 1	1/76 (1.32%)	0/78 (0.00%)
Diarrhoea † 1	4/76 (5.26%)	0/78 (0.00%)
Dysphagia † 1	2/76 (2.63%)	3/78 (3.85%)
Gastrointestinal haemorrhage † 1	1/76 (1.32%)	0/78 (0.00%)
Mouth haemorrhage † 1	0/76 (0.00%)	2/78 (2.56%)
Nausea † 1	1/76 (1.32%)	0/78 (0.00%)
Oesophageal obstruction † 1	0/76 (0.00%)	1/78 (1.28%)
Oesophagitis † 1	1/76 (1.32%)	0/78 (0.00%)
Oral cavity fistula † 1	1/76 (1.32%)	0/78 (0.00%)
Stomatitis † 1	1/76 (1.32%)	0/78 (0.00%)
Upper gastrointestinal haemorrhage † 1	1/76 (1.32%)	0/78 (0.00%)
Vomiting † 1	2/76 (2.63%)	0/78 (0.00%)
General disorders
Asthenia † 1	2/76 (2.63%)	2/78 (2.56%)
Face oedema † 1	0/76 (0.00%)	2/78 (2.56%)
Fatigue † 1	1/76 (1.32%)	4/78 (5.13%)
General physical health deterioration † 1	3/76 (3.95%)	0/78 (0.00%)
Non-cardiac chest pain † 1	1/76 (1.32%)	2/78 (2.56%)
Pain † 1	0/76 (0.00%)	1/78 (1.28%)
Pyrexia † 1	0/76 (0.00%)	2/78 (2.56%)
Systemic inflammatory response syndrome † 1	0/76 (0.00%)	1/78 (1.28%)
Hepatobiliary disorders
Hepatic failure † 1	1/76 (1.32%)	0/78 (0.00%)
Jaundice † 1	1/76 (1.32%)	0/78 (0.00%)
Infections and infestations
Anal abscess † 1	2/76 (2.63%)	0/78 (0.00%)
Bronchitis † 1	1/76 (1.32%)	2/78 (2.56%)
Candida sepsis † 1	1/76 (1.32%)	0/78 (0.00%)
Chest wall abscess † 1	0/76 (0.00%)	1/78 (1.28%)
Clostridium difficile colitis † 1	1/76 (1.32%)	0/78 (0.00%)
Erysipelas † 1	0/76 (0.00%)	1/78 (1.28%)
Herpes zoster † 1	1/76 (1.32%)	0/78 (0.00%)
Lower respiratory tract infection † 1	0/76 (0.00%)	1/78 (1.28%)
Lung abscess † 1	1/76 (1.32%)	1/78 (1.28%)
Lung infection † 1	2/76 (2.63%)	0/78 (0.00%)
Pneumonia † 1	6/76 (7.89%)	6/78 (7.69%)
Post procedural infection † 1	1/76 (1.32%)	0/78 (0.00%)
Pulmonary tuberculosis † 1	1/76 (1.32%)	0/78 (0.00%)
Respiratory tract infection † 1	1/76 (1.32%)	0/78 (0.00%)
Sepsis † 1	0/76 (0.00%)	1/78 (1.28%)
Septic shock † 1	3/76 (3.95%)	1/78 (1.28%)
Urinary tract infection † 1	1/76 (1.32%)	0/78 (0.00%)
Wound infection † 1	2/76 (2.63%)	0/78 (0.00%)
Injury, poisoning and procedural complications
Femur fracture † 1	0/76 (0.00%)	1/78 (1.28%)
Post procedural discharge † 1	1/76 (1.32%)	0/78 (0.00%)
Post procedural fistula † 1	0/76 (0.00%)	1/78 (1.28%)
Post procedural haemorrhage † 1	0/76 (0.00%)	1/78 (1.28%)
Spinal compression fracture † 1	0/76 (0.00%)	1/78 (1.28%)
Investigations
Blood creatinine increased † 1	1/76 (1.32%)	0/78 (0.00%)
Neutrophil count decreased † 1	1/76 (1.32%)	0/78 (0.00%)
Metabolism and nutrition disorders
Cachexia † 1	1/76 (1.32%)	3/78 (3.85%)
Decreased appetite † 1	3/76 (3.95%)	2/78 (2.56%)
Dehydration † 1	2/76 (2.63%)	1/78 (1.28%)
Hypercalcaemia † 1	1/76 (1.32%)	1/78 (1.28%)
Hyperglycaemia † 1	3/76 (3.95%)	0/78 (0.00%)
Hypocalcaemia † 1	1/76 (1.32%)	0/78 (0.00%)
Hypoglycaemia † 1	1/76 (1.32%)	0/78 (0.00%)
Hypokalaemia † 1	1/76 (1.32%)	2/78 (2.56%)
Hypomagnesaemia † 1	1/76 (1.32%)	0/78 (0.00%)
Musculoskeletal and connective tissue disorders
Spinal pain † 1	1/76 (1.32%)	0/78 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † 1	0/76 (0.00%)	1/78 (1.28%)
Malignant neoplasm progression † 1	0/76 (0.00%)	1/78 (1.28%)
Tumour haemorrhage † 1	3/76 (3.95%)	5/78 (6.41%)
Tumour invasion † 1	0/76 (0.00%)	1/78 (1.28%)
Nervous system disorders
Dizziness † 1	0/76 (0.00%)	1/78 (1.28%)
Hypoaesthesia † 1	1/76 (1.32%)	0/78 (0.00%)
Intracranial pressure increased † 1	0/76 (0.00%)	1/78 (1.28%)
Ischaemic cerebral infarction † 1	1/76 (1.32%)	0/78 (0.00%)
Neuralgia † 1	1/76 (1.32%)	0/78 (0.00%)
Paraplegia † 1	1/76 (1.32%)	0/78 (0.00%)
Somnolence † 1	1/76 (1.32%)	0/78 (0.00%)
Spinal cord compression † 1	1/76 (1.32%)	0/78 (0.00%)
Syncope † 1	1/76 (1.32%)	2/78 (2.56%)
Product Issues
Device connection issue † 1	1/76 (1.32%)	0/78 (0.00%)
Psychiatric disorders
Acute psychosis † 1	0/76 (0.00%)	1/78 (1.28%)
Aggression † 1	1/76 (1.32%)	0/78 (0.00%)
Completed suicide † 1	1/76 (1.32%)	0/78 (0.00%)
Mental status changes † 1	1/76 (1.32%)	0/78 (0.00%)
Renal and urinary disorders
Renal failure † 1	1/76 (1.32%)	0/78 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	0/76 (0.00%)	2/78 (2.56%)
Dyspnoea † 1	2/76 (2.63%)	2/78 (2.56%)
Haemoptysis † 1	1/76 (1.32%)	1/78 (1.28%)
Pneumonia aspiration † 1	1/76 (1.32%)	0/78 (0.00%)
Pneumonitis † 1	1/76 (1.32%)	0/78 (0.00%)
Pneumothorax † 1	1/76 (1.32%)	2/78 (2.56%)
Pulmonary embolism † 1	1/76 (1.32%)	0/78 (0.00%)
Respiratory arrest † 1	1/76 (1.32%)	1/78 (1.28%)
Respiratory failure † 1	1/76 (1.32%)	2/78 (2.56%)
Upper airway obstruction † 1	1/76 (1.32%)	0/78 (0.00%)
Skin and subcutaneous tissue disorders
Erythema † 1	1/76 (1.32%)	0/78 (0.00%)
Vascular disorders
Arterial rupture † 1	1/76 (1.32%)	0/78 (0.00%)
Hypotension † 1	1/76 (1.32%)	1/78 (1.28%)
Phlebitis † 1	1/76 (1.32%)	0/78 (0.00%)
1 Term from vocabulary, MedDRA (19.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	76/76 (100.00%)	75/78 (96.15%)
Blood and lymphatic system disorders
Anaemia † 1	29/76 (38.16%)	32/78 (41.03%)
Leukopenia † 1	7/76 (9.21%)	13/78 (16.67%)
Neutropenia † 1	23/76 (30.26%)	10/78 (12.82%)
Gastrointestinal disorders
Abdominal pain † 1	7/76 (9.21%)	2/78 (2.56%)
Constipation † 1	14/76 (18.42%)	8/78 (10.26%)
Diarrhoea † 1	26/76 (34.21%)	13/78 (16.67%)
Dyspepsia † 1	4/76 (5.26%)	2/78 (2.56%)
Dysphagia † 1	9/76 (11.84%)	5/78 (6.41%)
Nausea † 1	19/76 (25.00%)	13/78 (16.67%)
Odynophagia † 1	4/76 (5.26%)	1/78 (1.28%)
Oral pain † 1	4/76 (5.26%)	1/78 (1.28%)
Stomatitis † 1	23/76 (30.26%)	10/78 (12.82%)
Vomiting † 1	19/76 (25.00%)	11/78 (14.10%)
General disorders
Asthenia † 1	20/76 (26.32%)	15/78 (19.23%)
Face oedema † 1	2/76 (2.63%)	4/78 (5.13%)
Fatigue † 1	31/76 (40.79%)	16/78 (20.51%)
Non-cardiac chest pain † 1	2/76 (2.63%)	4/78 (5.13%)
Oedema peripheral † 1	5/76 (6.58%)	10/78 (12.82%)
Pyrexia † 1	12/76 (15.79%)	16/78 (20.51%)
Infections and infestations
Nasopharyngitis † 1	4/76 (5.26%)	4/78 (5.13%)
Pneumonia † 1	2/76 (2.63%)	6/78 (7.69%)
Respiratory tract infection † 1	5/76 (6.58%)	2/78 (2.56%)
Upper respiratory tract infection † 1	1/76 (1.32%)	4/78 (5.13%)
Investigations
Alanine aminotransferase increased † 1	6/76 (7.89%)	4/78 (5.13%)
Aspartate aminotransferase increased † 1	6/76 (7.89%)	7/78 (8.97%)
Blood alkaline phosphatase increased † 1	6/76 (7.89%)	1/78 (1.28%)
Blood creatinine increased † 1	4/76 (5.26%)	1/78 (1.28%)
Blood glucose increased † 1	3/76 (3.95%)	4/78 (5.13%)
Blood lactate dehydrogenase increased † 1	5/76 (6.58%)	5/78 (6.41%)
Gamma-glutamyltransferase increased † 1	8/76 (10.53%)	7/78 (8.97%)
Neutrophil count decreased † 1	5/76 (6.58%)	4/78 (5.13%)
Weight decreased † 1	19/76 (25.00%)	9/78 (11.54%)
White blood cell count decreased † 1	7/76 (9.21%)	3/78 (3.85%)
Metabolism and nutrition disorders
Decreased appetite † 1	23/76 (30.26%)	14/78 (17.95%)
Hyperglycaemia † 1	47/76 (61.84%)	27/78 (34.62%)
Hyperkalaemia † 1	2/76 (2.63%)	8/78 (10.26%)
Hypoalbuminaemia † 1	4/76 (5.26%)	3/78 (3.85%)
Hypocalcaemia † 1	5/76 (6.58%)	4/78 (5.13%)
Hypokalaemia † 1	7/76 (9.21%)	3/78 (3.85%)
Hypomagnesaemia † 1	4/76 (5.26%)	6/78 (7.69%)
Hyponatraemia † 1	5/76 (6.58%)	6/78 (7.69%)
Hypophosphataemia † 1	3/76 (3.95%)	5/78 (6.41%)
Musculoskeletal and connective tissue disorders
Back pain † 1	0/76 (0.00%)	6/78 (7.69%)
Muscle spasms † 1	4/76 (5.26%)	3/78 (3.85%)
Muscular weakness † 1	0/76 (0.00%)	5/78 (6.41%)
Musculoskeletal pain † 1	5/76 (6.58%)	2/78 (2.56%)
Myalgia † 1	4/76 (5.26%)	1/78 (1.28%)
Neck pain † 1	6/76 (7.89%)	7/78 (8.97%)
Pain in extremity † 1	1/76 (1.32%)	5/78 (6.41%)
Pain in jaw † 1	5/76 (6.58%)	1/78 (1.28%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain † 1	5/76 (6.58%)	2/78 (2.56%)
Nervous system disorders
Dizziness † 1	6/76 (7.89%)	6/78 (7.69%)
Dysgeusia † 1	4/76 (5.26%)	1/78 (1.28%)
Headache † 1	14/76 (18.42%)	6/78 (7.69%)
Neuropathy peripheral † 1	6/76 (7.89%)	18/78 (23.08%)
Paraesthesia † 1	8/76 (10.53%)	9/78 (11.54%)
Peripheral sensory neuropathy † 1	6/76 (7.89%)	3/78 (3.85%)
Psychiatric disorders
Anxiety † 1	13/76 (17.11%)	9/78 (11.54%)
Depression † 1	13/76 (17.11%)	7/78 (8.97%)
Insomnia † 1	10/76 (13.16%)	6/78 (7.69%)
Mood altered † 1	4/76 (5.26%)	5/78 (6.41%)
Respiratory, thoracic and mediastinal disorders
Catarrh † 1	1/76 (1.32%)	4/78 (5.13%)
Cough † 1	17/76 (22.37%)	18/78 (23.08%)
Dysphonia † 1	3/76 (3.95%)	4/78 (5.13%)
Dyspnoea † 1	8/76 (10.53%)	13/78 (16.67%)
Epistaxis † 1	7/76 (9.21%)	4/78 (5.13%)
Haemoptysis † 1	1/76 (1.32%)	7/78 (8.97%)
Hiccups † 1	5/76 (6.58%)	3/78 (3.85%)
Oropharyngeal pain † 1	5/76 (6.58%)	6/78 (7.69%)
Pneumonitis † 1	4/76 (5.26%)	3/78 (3.85%)
Productive cough † 1	4/76 (5.26%)	3/78 (3.85%)
Skin and subcutaneous tissue disorders
Alopecia † 1	24/76 (31.58%)	15/78 (19.23%)
Dermatitis acneiform † 1	5/76 (6.58%)	1/78 (1.28%)
Dry skin † 1	8/76 (10.53%)	2/78 (2.56%)
Erythema † 1	8/76 (10.53%)	2/78 (2.56%)
Onycholysis † 1	0/76 (0.00%)	4/78 (5.13%)
Palmar-plantar erythrodysaesthesia syndrome † 1	4/76 (5.26%)	0/78 (0.00%)
Pruritus † 1	8/76 (10.53%)	3/78 (3.85%)
Rash † 1	14/76 (18.42%)	11/78 (14.10%)
Rash maculo-papular † 1	5/76 (6.58%)	3/78 (3.85%)
Vascular disorders
Hypertension † 1	11/76 (14.47%)	6/78 (7.69%)
1 Term from vocabulary, MedDRA (19.1); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300
• EMail: novartis.email@novartis.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT01852292
• Other Study ID Numbers: CBKM120H2201; 2013-000744-26 ( EudraCT Number )
• First Submitted: May 8, 2013
• First Posted: May 13, 2013
• Results First Submitted: March 30, 2018
• Results First Posted: June 26, 2018
• Last Update Posted: July 24, 2018