Trial Outcomes & Findings for Safety and Efficacy of BKM120 in Patients With Metastatic Non-small Cell Lung Cancer (NCT NCT01297491)

NCT ID: NCT01297491

Last Updated: 2016-03-11

Results Overview

PFS rate was defined as the percentage of participants who were progression free at 12 weeks. Participants were considered as a "success" for PFS rate evaluated at 12 weeks if they presented an overall response at their 2nd post-baseline tumor assessment.The enrollment into the study in either histology group would stop for futility if a PFS rate \<50% at 12 weeks was observed. No statistical analysis was planned for this primary outcome. The results of the primary objective was based on the data from the interim analysis that took place at the cut off dates: 10-Apr-2013 for non-squamous and 08-Jan-2014 for squamous group.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

Week 12

Results posted on

2016-03-11

Participant Flow

Participant milestones

Participant milestones
Measure
Squamous BKM120 100mg qd
Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease.
Non-Squamous BKM120 100mg qd
Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
Overall Study
STARTED
30
33
Overall Study
COMPLETED
0
0
Overall Study
NOT COMPLETED
30
33

Reasons for withdrawal

Reasons for withdrawal
Measure
Squamous BKM120 100mg qd
Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease.
Non-Squamous BKM120 100mg qd
Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
Overall Study
Adverse Event
11
6
Overall Study
Physician Decision
3
2
Overall Study
Progressive disease
11
20
Overall Study
Patient/Guardian decision
3
4
Overall Study
Death
2
1

Baseline Characteristics

Safety and Efficacy of BKM120 in Patients With Metastatic Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Squamous BKM120 100mg qd
n=30 Participants
Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease.
Non-Squamous BKM120 100mg qd
n=33 Participants
Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
Total
n=63 Participants
Total of all reporting groups
Age, Customized
< 65 years
12 Participants
n=5 Participants
19 Participants
n=7 Participants
31 Participants
n=5 Participants
Age, Customized
>= 65 years
18 Participants
n=5 Participants
14 Participants
n=7 Participants
32 Participants
n=5 Participants
Sex: Female, Male
Female
9 Participants
n=5 Participants
14 Participants
n=7 Participants
23 Participants
n=5 Participants
Sex: Female, Male
Male
21 Participants
n=5 Participants
19 Participants
n=7 Participants
40 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Week 12

Population: Analysis set Stage 1 includes all patients who were enrolled during Stage 1 after meeting eligibility criteria and who have received at least one dose of study drug.

PFS rate was defined as the percentage of participants who were progression free at 12 weeks. Participants were considered as a "success" for PFS rate evaluated at 12 weeks if they presented an overall response at their 2nd post-baseline tumor assessment.The enrollment into the study in either histology group would stop for futility if a PFS rate \<50% at 12 weeks was observed. No statistical analysis was planned for this primary outcome. The results of the primary objective was based on the data from the interim analysis that took place at the cut off dates: 10-Apr-2013 for non-squamous and 08-Jan-2014 for squamous group.

Outcome measures

Outcome measures
Measure
Squamous BKM120 100mg qd
n=30 Participants
Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease.
Non-Squamous BKM120 100mg qd
n=30 Participants
Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
Progression Free Survival (PFS) Rate as Per Investigator Local Review Measured Using RECIST 1.1 of Patients at Week 12
23.3 Percentage of participants
Interval 9.9 to 42.3
20.0 Percentage of participants
Interval 7.7 to 38.6

SECONDARY outcome

Timeframe: Every 8 weeks up to 24 months

Population: Analysis set Stage 1 includes all patients who were enrolled during Stage 1 after meeting eligibility criteria and who have received at least one dose of study drug.

OS was defined as the time from start of study drug (Stage 1) until death from any cause. If a patient was not known to have died, survival was censored at the date of last contact.

Outcome measures

Outcome measures
Measure
Squamous BKM120 100mg qd
n=30 Participants
Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease.
Non-Squamous BKM120 100mg qd
n=33 Participants
Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
Overall Survival (OS) Using Kaplan-Meier Estimates
7.98 Months
Interval 5.95 to 10.09
7.20 Months
Interval 4.01 to 9.92

SECONDARY outcome

Timeframe: Every 6 weeks up to 24 months

Population: Analysis set Stage 1 includes all patients who were enrolled during Stage 1 after meeting eligibility criteria and who have received at least one dose of study drug.

ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR). Complete response was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Partial response was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Analyses of response rates were performed based on investigators' assessments (as per RECIST 1.1 criteria). ORR included all patients with and without measurable disease at baseline.

Outcome measures

Outcome measures
Measure
Squamous BKM120 100mg qd
n=30 Participants
Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease.
Non-Squamous BKM120 100mg qd
n=33 Participants
Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
Overall Response Rate (ORR) Based on Investigator Assessment
3.3 Percentage of participants
3.0 Percentage of participants

SECONDARY outcome

Timeframe: Every 6 weeks up tp 24 months

Population: Analysis set Stage 1 includes all patients who were enrolled during Stage 1 after meeting eligibility criteria and who have received at least one dose of study drug.

DCR defined as the percentage of participants with best overall response of CR or PR or stable disease (SD). Complete response was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Partial response was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Analyses of response rates were performed based on investigators' assessments (as per RECIST 1.1 criteria). DCR included all participants with and without measurable disease at baseline.

Outcome measures

Outcome measures
Measure
Squamous BKM120 100mg qd
n=30 Participants
Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease.
Non-Squamous BKM120 100mg qd
n=33 Participants
Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
Disease Control Rate (DCR)
46.7 Percentage of participants
45.5 Percentage of participants

SECONDARY outcome

Timeframe: Every 6 weeks up to 24 months

Population: Analysis set Stage 1 includes all patients who were enrolled during Stage 1 after meeting eligibility criteria and who have received at least 1 dose of study drug. 1 partial response was observed as best overall response (BOR) for 1 patient in the squamous group. Also,1 patient experienced partial response as BOR in the non-squamous group.

TTR for a participant was defined as the time from the first treatment date to the date of first documented confirmed CR or PR evaluation. The date of event was defined as the date of response that was first determined and not using the date the response was confirmed.

Outcome measures

Outcome measures
Measure
Squamous BKM120 100mg qd
n=30 Participants
Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease.
Non-Squamous BKM120 100mg qd
n=33 Participants
Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
Time to Response (TTR)
41 Days
42 Days

SECONDARY outcome

Timeframe: Every 6 weeks up to 24 months

Population: Analysis set Stage 1 includes all patients who were enrolled during Stage 1 after meeting eligibility criteria and who have received at least 1 dose of study drug. 1 partial response was observed as best overall response (BOR) for 1 patient in the squamous group. Also,1 patient experienced partial response as BOR in the non-squamous group.

DoR was defined as the elapsed time between the date of first documented CR or PR response (not the date of confirmed response) and the following date of event defined as the first documented progression or death due to underlying cancer.

Outcome measures

Outcome measures
Measure
Squamous BKM120 100mg qd
n=30 Participants
Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease.
Non-Squamous BKM120 100mg qd
n=33 Participants
Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
Duration of Response (DoR)
73 Days
85 Days

Adverse Events

Squamous BKM120 100 mg qd

Serious events: 16 serious events
Other events: 29 other events
Deaths: 0 deaths

Non-Squamous BKM120 100 mg qd

Serious events: 15 serious events
Other events: 32 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Squamous BKM120 100 mg qd
n=30 participants at risk
Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease.
Non-Squamous BKM120 100 mg qd
n=33 participants at risk
Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
Blood and lymphatic system disorders
Anaemia
3.3%
1/30
0.00%
0/33
Cardiac disorders
Cardiac failure
3.3%
1/30
0.00%
0/33
Cardiac disorders
Cardiogenic shock
0.00%
0/30
3.0%
1/33
Cardiac disorders
Myocardial infarction
3.3%
1/30
0.00%
0/33
Cardiac disorders
Supraventricular tachycardia
3.3%
1/30
0.00%
0/33
Eye disorders
Blepharitis
0.00%
0/30
3.0%
1/33
Gastrointestinal disorders
Diarrhoea
0.00%
0/30
3.0%
1/33
Gastrointestinal disorders
Enteritis
0.00%
0/30
3.0%
1/33
Gastrointestinal disorders
Ileus
3.3%
1/30
0.00%
0/33
General disorders
Asthenia
3.3%
1/30
0.00%
0/33
General disorders
Fatigue
0.00%
0/30
3.0%
1/33
General disorders
General physical health deterioration
13.3%
4/30
0.00%
0/33
General disorders
Local swelling
3.3%
1/30
0.00%
0/33
Hepatobiliary disorders
Hepatitis toxic
0.00%
0/30
3.0%
1/33
Infections and infestations
Escherichia sepsis
3.3%
1/30
0.00%
0/33
Infections and infestations
Lower respiratory tract infection
0.00%
0/30
3.0%
1/33
Infections and infestations
Lung abscess
0.00%
0/30
3.0%
1/33
Infections and infestations
Lung infection
3.3%
1/30
0.00%
0/33
Infections and infestations
Pneumonia
10.0%
3/30
3.0%
1/33
Infections and infestations
Sepsis
3.3%
1/30
0.00%
0/33
Infections and infestations
Urinary tract infection
0.00%
0/30
3.0%
1/33
Infections and infestations
Urinary tract infection pseudomonal
3.3%
1/30
0.00%
0/33
Investigations
Alanine aminotransferase increased
3.3%
1/30
0.00%
0/33
Investigations
Aspartate aminotransferase increased
3.3%
1/30
0.00%
0/33
Metabolism and nutrition disorders
Dehydration
6.7%
2/30
0.00%
0/33
Metabolism and nutrition disorders
Hyperglycaemia
6.7%
2/30
9.1%
3/33
Metabolism and nutrition disorders
Hyponatraemia
3.3%
1/30
0.00%
0/33
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
3.3%
1/30
0.00%
0/33
Musculoskeletal and connective tissue disorders
Pain in extremity
3.3%
1/30
0.00%
0/33
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
3.3%
1/30
0.00%
0/33
Nervous system disorders
Cerebral ischaemia
0.00%
0/30
3.0%
1/33
Nervous system disorders
Dizziness
3.3%
1/30
0.00%
0/33
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
3.3%
1/30
0.00%
0/33
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
3.3%
1/30
0.00%
0/33
Respiratory, thoracic and mediastinal disorders
Dyspnoea
3.3%
1/30
9.1%
3/33
Respiratory, thoracic and mediastinal disorders
Epistaxis
0.00%
0/30
3.0%
1/33
Respiratory, thoracic and mediastinal disorders
Haemoptysis
3.3%
1/30
3.0%
1/33
Respiratory, thoracic and mediastinal disorders
Hypoxia
3.3%
1/30
0.00%
0/33
Respiratory, thoracic and mediastinal disorders
Pneumonitis
3.3%
1/30
0.00%
0/33
Respiratory, thoracic and mediastinal disorders
Respiratory failure
0.00%
0/30
9.1%
3/33
Skin and subcutaneous tissue disorders
Dermatitis allergic
3.3%
1/30
0.00%
0/33
Skin and subcutaneous tissue disorders
Rash
3.3%
1/30
3.0%
1/33
Skin and subcutaneous tissue disorders
Rash macular
0.00%
0/30
3.0%
1/33
Vascular disorders
Thrombosis
0.00%
0/30
3.0%
1/33

Other adverse events

Other adverse events
Measure
Squamous BKM120 100 mg qd
n=30 participants at risk
Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease.
Non-Squamous BKM120 100 mg qd
n=33 participants at risk
Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease.
Blood and lymphatic system disorders
Anaemia
16.7%
5/30
6.1%
2/33
Blood and lymphatic system disorders
Thrombocytopenia
6.7%
2/30
0.00%
0/33
Cardiac disorders
Sinus tachycardia
6.7%
2/30
0.00%
0/33
Ear and labyrinth disorders
Tinnitus
0.00%
0/30
6.1%
2/33
Eye disorders
Lacrimation increased
6.7%
2/30
3.0%
1/33
Eye disorders
Vision blurred
10.0%
3/30
6.1%
2/33
Gastrointestinal disorders
Abdominal pain upper
10.0%
3/30
3.0%
1/33
Gastrointestinal disorders
Constipation
16.7%
5/30
9.1%
3/33
Gastrointestinal disorders
Diarrhoea
36.7%
11/30
33.3%
11/33
Gastrointestinal disorders
Dry mouth
6.7%
2/30
3.0%
1/33
Gastrointestinal disorders
Dyspepsia
6.7%
2/30
0.00%
0/33
Gastrointestinal disorders
Dysphagia
3.3%
1/30
6.1%
2/33
Gastrointestinal disorders
Nausea
43.3%
13/30
27.3%
9/33
Gastrointestinal disorders
Stomatitis
6.7%
2/30
12.1%
4/33
Gastrointestinal disorders
Vomiting
20.0%
6/30
15.2%
5/33
General disorders
Asthenia
20.0%
6/30
36.4%
12/33
General disorders
Fatigue
36.7%
11/30
18.2%
6/33
General disorders
Hypothermia
0.00%
0/30
6.1%
2/33
General disorders
Non-cardiac chest pain
10.0%
3/30
3.0%
1/33
General disorders
Oedema peripheral
10.0%
3/30
3.0%
1/33
General disorders
Pain
3.3%
1/30
6.1%
2/33
General disorders
Pyrexia
6.7%
2/30
12.1%
4/33
Infections and infestations
Bronchitis
13.3%
4/30
0.00%
0/33
Infections and infestations
Candida infection
6.7%
2/30
0.00%
0/33
Infections and infestations
Conjunctivitis
3.3%
1/30
9.1%
3/33
Infections and infestations
Lower respiratory tract infection
6.7%
2/30
0.00%
0/33
Infections and infestations
Rhinitis
0.00%
0/30
6.1%
2/33
Investigations
Alanine aminotransferase increased
20.0%
6/30
18.2%
6/33
Investigations
Aspartate aminotransferase increased
16.7%
5/30
18.2%
6/33
Investigations
Blood alkaline phosphatase increased
10.0%
3/30
3.0%
1/33
Investigations
Blood creatinine increased
6.7%
2/30
3.0%
1/33
Investigations
Blood glucose increased
6.7%
2/30
3.0%
1/33
Investigations
Blood lactate dehydrogenase increased
6.7%
2/30
6.1%
2/33
Investigations
Blood urea increased
6.7%
2/30
0.00%
0/33
Investigations
Gamma-glutamyltransferase increased
10.0%
3/30
6.1%
2/33
Investigations
Insulin c-peptide increased
0.00%
0/30
6.1%
2/33
Investigations
Transaminases increased
6.7%
2/30
6.1%
2/33
Investigations
Weight decreased
26.7%
8/30
9.1%
3/33
Metabolism and nutrition disorders
Decreased appetite
36.7%
11/30
36.4%
12/33
Metabolism and nutrition disorders
Dehydration
6.7%
2/30
0.00%
0/33
Metabolism and nutrition disorders
Hyperglycaemia
36.7%
11/30
33.3%
11/33
Metabolism and nutrition disorders
Hypokalaemia
3.3%
1/30
6.1%
2/33
Metabolism and nutrition disorders
Hyponatraemia
6.7%
2/30
0.00%
0/33
Musculoskeletal and connective tissue disorders
Back pain
10.0%
3/30
9.1%
3/33
Musculoskeletal and connective tissue disorders
Bone pain
6.7%
2/30
0.00%
0/33
Musculoskeletal and connective tissue disorders
Muscle spasms
3.3%
1/30
6.1%
2/33
Musculoskeletal and connective tissue disorders
Muscular weakness
10.0%
3/30
3.0%
1/33
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
3.3%
1/30
6.1%
2/33
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
6.7%
2/30
6.1%
2/33
Musculoskeletal and connective tissue disorders
Neck pain
6.7%
2/30
0.00%
0/33
Musculoskeletal and connective tissue disorders
Pain in extremity
6.7%
2/30
9.1%
3/33
Nervous system disorders
Dizziness
6.7%
2/30
3.0%
1/33
Nervous system disorders
Dysgeusia
13.3%
4/30
12.1%
4/33
Nervous system disorders
Headache
13.3%
4/30
0.00%
0/33
Nervous system disorders
Memory impairment
6.7%
2/30
0.00%
0/33
Nervous system disorders
Myoclonus
6.7%
2/30
0.00%
0/33
Nervous system disorders
Neuropathy peripheral
3.3%
1/30
6.1%
2/33
Nervous system disorders
Somnolence
3.3%
1/30
6.1%
2/33
Nervous system disorders
Tremor
13.3%
4/30
3.0%
1/33
Psychiatric disorders
Anxiety
10.0%
3/30
24.2%
8/33
Psychiatric disorders
Confusional state
10.0%
3/30
3.0%
1/33
Psychiatric disorders
Depression
13.3%
4/30
33.3%
11/33
Psychiatric disorders
Insomnia
3.3%
1/30
6.1%
2/33
Psychiatric disorders
Mood altered
6.7%
2/30
12.1%
4/33
Renal and urinary disorders
Renal failure acute
6.7%
2/30
0.00%
0/33
Respiratory, thoracic and mediastinal disorders
Cough
20.0%
6/30
18.2%
6/33
Respiratory, thoracic and mediastinal disorders
Dyspnoea
20.0%
6/30
21.2%
7/33
Respiratory, thoracic and mediastinal disorders
Haemoptysis
3.3%
1/30
6.1%
2/33
Respiratory, thoracic and mediastinal disorders
Pneumonitis
10.0%
3/30
0.00%
0/33
Respiratory, thoracic and mediastinal disorders
Productive cough
3.3%
1/30
6.1%
2/33
Skin and subcutaneous tissue disorders
Acne
0.00%
0/30
6.1%
2/33
Skin and subcutaneous tissue disorders
Alopecia
3.3%
1/30
6.1%
2/33
Skin and subcutaneous tissue disorders
Dry skin
13.3%
4/30
15.2%
5/33
Skin and subcutaneous tissue disorders
Erythema
0.00%
0/30
9.1%
3/33
Skin and subcutaneous tissue disorders
Nail disorder
3.3%
1/30
6.1%
2/33
Skin and subcutaneous tissue disorders
Pruritus
36.7%
11/30
12.1%
4/33
Skin and subcutaneous tissue disorders
Rash
26.7%
8/30
18.2%
6/33
Skin and subcutaneous tissue disorders
Skin exfoliation
3.3%
1/30
6.1%
2/33
Vascular disorders
Hypertension
3.3%
1/30
6.1%
2/33
Vascular disorders
Hypotension
0.00%
0/30
6.1%
2/33

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

  • Principal investigator is a sponsor employee 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.
  • Publication restrictions are in place

Restriction type: OTHER