Trial of Erlotinib and BKM120 in Patients With Advanced Non Small Cell Lung Cancer Previously Sensitive to Erlotinib

• ClinicalTrials.gov Identifier: NCT01487265
• Recruitment Status: Completed
• First Posted: December 7, 2011
• Results First Posted: December 13, 2017
• Last Update Posted: March 6, 2019
• Sponsor: SCRI Development Innovations, LLC
• Collaborator: Novartis
• Information provided by (Responsible Party): SCRI Development Innovations, LLC

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non Small Cell Lung Cancer
• Intervention: Drug: BKM120 and Erlotinib
• Enrollment: 37

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Erlotinib + BKM120
Arm/Group Description	BKM120, administered 80 mg by mouth (PO) daily during the first week of Cycle 1, then escalated to 100 mg PO daily. Erlotinib, administered 100 mg PO daily. Each cycle is 28 days.
Period Title: Overall Study
Started	37
Completed	0
Not Completed	37
Reason Not Completed
Adverse Event	8
Withdrawal by Subject	5
Disease Progression	21
Death	2
Still on Treatment	1

Baseline Characteristics

Arm/Group Title		Erlotinib + BKM120
Arm/Group Description		BKM120, administered 80 mg by mouth (PO) daily during the first week of Cycle 1, then escalated to 100 mg PO daily. Erlotinib, administered 100 mg PO daily. Each cycle is 28 days.
Overall Number of Baseline Participants		37
Baseline Analysis Population Description		Patients that have received at least one dose of study treatment
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	37 participants
		69; (42 to 85)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	37 participants
	Female	22
	Male	15
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	37 participants
		37 100.0%
Smoking Status; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	37 participants
	Never smoker	19 51.4%
	Current smoker	2 5.4%
	Former smoker	16 43.2%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival at 3 Months
Description	Percentage of patients who are alive and progression-free at 3 months (APF3) from first treatment.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Patients that were treated with at least one dose of study treatment

Arm/Group Title	Erlotinib + BKM120
Arm/Group Description:	BKM120, administered 80 mg by mouth (PO) daily during the first week of Cycle 1, then escalated to 100 mg PO daily. Erlotinib, administered 100 mg PO daily. Each cycle is 28 days.
Overall Number of Participants Analyzed	37
Measure Type: Number; Unit of Measure: percentage of participants
	50.4

2. Secondary Outcome

Title	Overall Survival
Description	Defined as the time from first treatment until death from any cause.
Time Frame	every 3 months after study treatment, projected 24 months

Outcome Measure Data

Analysis Population Description

Patients that received at least one dose of study treatment

Arm/Group Title	Erlotinib + BKM120
Arm/Group Description:	BKM120, administered 80 mg by mouth (PO) daily during the first week of Cycle 1, then escalated to 100 mg PO daily. Erlotinib, administered 100 mg PO daily. Each cycle is 28 days.
Overall Number of Participants Analyzed	37
Median (95% Confidence Interval); Unit of Measure: months
	12.2; (7.2 to 33.3)

3. Secondary Outcome

Title	Duration of Response
Description	Defined as the time from complete or partial response (CR or PR) until objective tumor progression. Tumor measurements will be obtained using CT scans of chest, abdomen and pelvis and assessed per RECIST v 1.1. Complete response (CR) is defined as a disappearance of all lesions; partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking the baseline sum LD as reference. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for progressive disease, taking as reference the smallest (nadir) sum LD since start of treatment.
Time Frame	every 8 weeks for 12 months, then every 12 weeks thereafter, estimated 18 months

Outcome Measure Data

Analysis Population Description

Of 37 participates that received study treatment, only two participants met the minimum criteria to be included (one censored, and the remaining one analyzed for duration of response)

Arm/Group Title	Erlotinib + BKM120
Arm/Group Description:	BKM120, administered 80 mg by mouth (PO) daily during the first week of Cycle 1, then escalated to 100 mg PO daily. Erlotinib, administered 100 mg PO daily. Each cycle is 28 days.
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: months
	3.2

4. Secondary Outcome

Title	Objective Response Rate
Description	Defined as the percentage of complete and partial responses (CR + PR) among all patients. Complete response (CR) is defined as a disappearance of all lesions; partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking the baseline sum LD as reference. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for progressive disease, taking as reference the smallest (nadir) sum LD since start of treatment.
Time Frame	every 8 weeks for 12 months, then every 12 weeks thereafter, estimated 18 months

Outcome Measure Data

Analysis Population Description

patients that received at least one dose of study treatment

Arm/Group Title	Erlotinib + BKM120
Arm/Group Description:	BKM120, administered 80 mg by mouth (PO) daily during the first week of Cycle 1, then escalated to 100 mg PO daily. Erlotinib, administered 100 mg PO daily. Each cycle is 28 days.
Overall Number of Participants Analyzed	37
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	5.4; (0.7 to 18.2)

5. Secondary Outcome

Title	Number of Participants With Serious and Non-serious Adverse Events as a Measure of Safety.
Description	Adverse events will be graded using CTCAE v4.3. and will be collected until 30 days after the discontinuation of study treatment for each participant. A non-serious adverse event is any untoward medical occurrence. A serious adverse event (SAE) is an event that meets one or more of the following: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; requires intervention to prevent permanent impairment or damage. Specific AE and SAE terms are provided in the Adverse event module.
Time Frame	Every 2 weeks for 8 weeks, then every 8 weeks thereafter, estimated 24 months

Outcome Measure Data

Analysis Population Description

Patients that received at least one dose of study treatment

Arm/Group Title	Erlotinib + BKM120
Arm/Group Description:	BKM120, administered 80 mg by mouth (PO) daily during the first week of Cycle 1, then escalated to 100 mg PO daily. Erlotinib, administered 100 mg PO daily. Each cycle is 28 days.
Overall Number of Participants Analyzed	37
Measure Type: Number; Unit of Measure: participants
Adverse Events (all grades)	37
Serious Adverse Events	13

Adverse Events

Time Frame	Collected from the date of first treatment until 30 days after the discontinuation of study treatment, approximately months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Erlotinib + BKM120
Arm/Group Description	BKM120, administered 80 mg by mouth (PO) daily during the first week of Cycle 1, then escalated to 100 mg PO daily. Erlotinib, administered 100 mg PO daily. Each cycle is 28 days.
All-Cause Mortality
	Erlotinib + BKM120
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Erlotinib + BKM120
	Affected / at Risk (%)	# Events
Total	13/37 (35.14%)
Blood and lymphatic system disorders
Febrile neutropenia * 1	1/37 (2.70%)	1
Cardiac disorders
Supraventricular tachycardia * 1	1/37 (2.70%)	1
Gastrointestinal disorders
Diarrhoea * 1	2/37 (5.41%)	2
Gastrointestinal haemorrhage * 1	1/37 (2.70%)	1
General disorders
Asthenia * 1	1/37 (2.70%)	1
Disease progression * 1	1/37 (2.70%)	1
Pyrexia * 1	1/37 (2.70%)	1
Infections and infestations
Gastroenteritis * 1	1/37 (2.70%)	1
Pneumonia * 1	2/37 (5.41%)	2
Metabolism and nutrition disorders
Dehydration * 1	1/37 (2.70%)	1
Nervous system disorders
Vasogenic cerebral oedema * 1	1/37 (2.70%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea * 1	1/37 (2.70%)	1
Interstitial lung disease * 1	1/37 (2.70%)	1
Respiratory failure * 1	1/37 (2.70%)	1
Vascular disorders
Deep vein thrombosis * 1	1/37 (2.70%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Erlotinib + BKM120
	Affected / at Risk (%)	# Events
Total	37/37 (100.00%)
Cardiac disorders
Supraventricular Tachycardia † 1	2/37 (5.41%)
Eye disorders
Eye Pain † 1	2/37 (5.41%)
Vision Blurred † 1	2/37 (5.41%)
Gastrointestinal disorders
Diarrhoea † 1	29/37 (78.38%)
Nausea † 1	17/37 (45.95%)
Dyspepsia † 1	7/37 (18.92%)
Vomiting † 1	7/37 (18.92%)
Abdominal Pain † 1	4/37 (10.81%)
Gastrooesophageal Reflux Disease † 1	4/37 (10.81%)
Constipation † 1	3/37 (8.11%)
Dry Mouth † 1	3/37 (8.11%)
Stomatitis † 1	3/37 (8.11%)
General disorders
Fatigue † 1	20/37 (54.05%)
Oedema Peripheral † 1	5/37 (13.51%)
Asthenia † 1	4/37 (10.81%)
Mucosal Inflammation † 1	3/37 (8.11%)
Pain † 1	3/37 (8.11%)
Pyrexia † 1	3/37 (8.11%)
Chest Pain † 1	2/37 (5.41%)
Infections and infestations
Pneumonia † 1	4/37 (10.81%)
Urinary Tract Infection † 1	4/37 (10.81%)
Upper Respiratory Tract Infection † 1	2/37 (5.41%)
Investigations
Weight Decreased † 1	6/37 (16.22%)
Alanine Aminotransferase Increased † 1	3/37 (8.11%)
Metabolism and nutrition disorders
Decreased Appetite † 1	14/37 (37.84%)
Dehydration † 1	9/37 (24.32%)
Hyperglycaemia † 1	9/37 (24.32%)
Hypokalaemia † 1	5/37 (13.51%)
Hypomagnesaemia † 1	3/37 (8.11%)
Hypoalbuminaemia † 1	2/37 (5.41%)
Hypocalcaemia † 1	2/37 (5.41%)
Hyponatraemia † 1	2/37 (5.41%)
Musculoskeletal and connective tissue disorders
Muscle Spasms † 1	3/37 (8.11%)
Back Pain † 1	2/37 (5.41%)
Musculoskeletal Pain † 1	2/37 (5.41%)
Nervous system disorders
Dysgeusia † 1	8/37 (21.62%)
Headache † 1	6/37 (16.22%)
Dizziness † 1	5/37 (13.51%)
Syncope † 1	2/37 (5.41%)
Tremor † 1	2/37 (5.41%)
Psychiatric disorders
Depression † 1	5/37 (13.51%)
Insomnia † 1	5/37 (13.51%)
Anxiety † 1	4/37 (10.81%)
Confusional State † 1	3/37 (8.11%)
Irritability † 1	2/37 (5.41%)
Mood Altered † 1	2/37 (5.41%)
Renal and urinary disorders
Dysuria † 1	2/37 (5.41%)
Pollakiuria † 1	2/37 (5.41%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	8/37 (21.62%)
Dyspnoea † 1	7/37 (18.92%)
Epistaxis † 1	3/37 (8.11%)
Oropharyngeal Pain † 1	3/37 (8.11%)
Dyspnoea Exertional † 1	2/37 (5.41%)
Lower Respiratory Tract Congestion † 1	2/37 (5.41%)
Pleural Effusion † 1	2/37 (5.41%)
Pulmonary Embolism † 1	2/37 (5.41%)
Skin and subcutaneous tissue disorders
Rash † 1	10/37 (27.03%)
Dermatitis Acneiform † 1	7/37 (18.92%)
Dry Skin † 1	6/37 (16.22%)
Pruritus † 1	3/37 (8.11%)
Nail Disorder † 1	2/37 (5.41%)
Rash Maculo-Papular † 1	2/37 (5.41%)
Vascular disorders
Deep Vein Thrombosis † 1	3/37 (8.11%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA

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 sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.

Results Point of Contact

• Name/Title: Charles H. Davis
• Organization: Sarah Cannon Research Institute
• Phone: 615-524-4341
• EMail: charles.davis2@scri-innovations.com

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT01487265
• Other Study ID Numbers: SCRI LUN 214
• First Submitted: December 1, 2011
• First Posted: December 7, 2011
• Results First Submitted: August 17, 2017
• Results First Posted: December 13, 2017
• Last Update Posted: March 6, 2019