Trial Outcomes & Findings for Dose Escalation of Bevacizumab With Ambulatory Blood Pressure Monitoring in Patients With Advanced Non-squamous NSCLC (NCT NCT01063283)

NCT ID: NCT01063283

Last Updated: 2019-11-18

Results Overview

The change for each patient was calculated as mean 24 hour DBP during cycle 2 - mean 24 hour DBP during cycle 1

Recruitment status

COMPLETED

Study phase

Target enrollment

20 participants

Primary outcome timeframe

2 cycles

Results posted on

2019-11-18

Participant Flow

All enrolled patients received one cycle and those who tolerated it and had no evidence of risk for dose escalation were randomized to receive one of two treatment regimens.

Participant milestones

Participant milestones
Measure	All Participants All participants enrolled received Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once during the first cycle.	Group A Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once during first cycle, followed three weeks later by Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg and bevacizumab every 3 weeks for two doses	Group B Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once during first cycle, followed three weeks later by Carboplatin+Pemetrexed+Bevacizumab 15 mg/kg and bevacizumab every 3 weeks for two doses
Cycle 1 STARTED	20	0	0
Cycle 1 COMPLETED	17	0	0
Cycle 1 NOT COMPLETED	3	0	0
Randomized Phase (Cycle 2 and Beyond) STARTED	0	6	11
Randomized Phase (Cycle 2 and Beyond) COMPLETED	0	6	11
Randomized Phase (Cycle 2 and Beyond) NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	All Participants All participants enrolled received Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once during the first cycle.	Group A Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once during first cycle, followed three weeks later by Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg and bevacizumab every 3 weeks for two doses	Group B Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once during first cycle, followed three weeks later by Carboplatin+Pemetrexed+Bevacizumab 15 mg/kg and bevacizumab every 3 weeks for two doses
Cycle 1 Adverse Event	2	0	0
Cycle 1 Technical failure in data collection	1	0	0

Baseline Characteristics

Dose Escalation of Bevacizumab With Ambulatory Blood Pressure Monitoring in Patients With Advanced Non-squamous NSCLC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=6 Participants Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once, followed three weeks later by Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg and bevacizumab every 3 weeks for two doses	Group B n=11 Participants Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once, followed three weeks later by Carboplatin+Pemetrexed+Bevacizumab 15 mg/kg and bevacizumab every 3 weeks for two doses	Total n=17 Participants Total of all reporting groups
Age, Continuous	53 years n=5 Participants	59 years n=7 Participants	57 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized White non-Hispanic	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Black non-Hispanic	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	11 participants n=7 Participants	17 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 cycles

The change for each patient was calculated as mean 24 hour DBP during cycle 2 - mean 24 hour DBP during cycle 1

Outcome measures

Outcome measures
Measure	Group A n=6 Participants Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once, followed three weeks later by Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg and bevacizumab every 3 weeks for two doses	Group B n=11 Participants Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once, followed three weeks later by Carboplatin+Pemetrexed+Bevacizumab 15 mg/kg and bevacizumab every 3 weeks for two doses
Change in 24 Hour Diastolic Blood Pressure (DBP)	3 mmHg Standard Deviation 4	3 mmHg Standard Deviation 10

SECONDARY outcome

Timeframe: 2 years

Percentage of patients with a complete or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Group A n=6 Participants Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once, followed three weeks later by Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg and bevacizumab every 3 weeks for two doses	Group B n=11 Participants Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once, followed three weeks later by Carboplatin+Pemetrexed+Bevacizumab 15 mg/kg and bevacizumab every 3 weeks for two doses
Response Rate	3 Participants	2 Participants

SECONDARY outcome

Timeframe: 2 years

Population: Because the study did not meet its accrual goals, the study team did not proceed to collect this secondary outcome measure. The data were not collected and therefore are not available to report.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Time to progression or death from any cause, whichever comes first

Outcome measures

Outcome data not reported

Adverse Events

Group A

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Group B

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group A n=6 participants at risk Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once, followed three weeks later by Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg and bevacizumab every 3 weeks for two doses	Group B n=11 participants at risk Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once, followed three weeks later by Carboplatin+Pemetrexed+Bevacizumab 15 mg/kg and bevacizumab every 3 weeks for two doses
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Vascular disorders Hypotension	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.

Other adverse events

Additional Information

Michael Maitland, MD, PhD

Inova

Phone: 571-472-4724

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Group A n=6 participants at risk Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once, followed three weeks later by Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg and bevacizumab every 3 weeks for two doses	Group B n=11 participants at risk Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once, followed three weeks later by Carboplatin+Pemetrexed+Bevacizumab 15 mg/kg and bevacizumab every 3 weeks for two doses
Gastrointestinal disorders GERD	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Skin and subcutaneous tissue disorders Intermittent periorbital edema	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Infections and infestations Sinus infection	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Infections and infestations Thrush	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Infections and infestations otitis externa	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	18.2% 2/11 • 6 months Other adverse events grade 2 or higher are reported.
Cardiac disorders heart murmur	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Infections and infestations Hepatitis	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Blood and lymphatic system disorders Anemia	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Skin and subcutaneous tissue disorders Alopecia	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	27.3% 3/11 • 6 months Other adverse events grade 2 or higher are reported.
General disorders Chest pain	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Gastrointestinal disorders Constipation	33.3% 2/6 • 6 months Other adverse events grade 2 or higher are reported.	18.2% 2/11 • 6 months Other adverse events grade 2 or higher are reported.
Metabolism and nutrition disorders Dehydration	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	18.2% 2/11 • 6 months Other adverse events grade 2 or higher are reported.
General disorders Diaphoresis	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	0.00% 0/11 • 6 months Other adverse events grade 2 or higher are reported.
Nervous system disorders Dysgeusia	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	0.00% 0/11 • 6 months Other adverse events grade 2 or higher are reported.
Vascular disorders Hypertension	33.3% 2/6 • 6 months Other adverse events grade 2 or higher are reported.	36.4% 4/11 • 6 months Other adverse events grade 2 or higher are reported.
Investigations Alanine aminotransferase increased	33.3% 2/6 • 6 months Other adverse events grade 2 or higher are reported.	0.00% 0/11 • 6 months Other adverse events grade 2 or higher are reported.
Investigations Aspartate aminotransferase increased	33.3% 2/6 • 6 months Other adverse events grade 2 or higher are reported.	0.00% 0/11 • 6 months Other adverse events grade 2 or higher are reported.
Eye disorders Retinal tear	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	0.00% 0/11 • 6 months Other adverse events grade 2 or higher are reported.
Gastrointestinal disorders Dyspepsia	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	0.00% 0/11 • 6 months Other adverse events grade 2 or higher are reported.
General disorders pain	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	36.4% 4/11 • 6 months Other adverse events grade 2 or higher are reported.
Gastrointestinal disorders Oral pain	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	0.00% 0/11 • 6 months Other adverse events grade 2 or higher are reported.
Gastrointestinal disorders Vomiting	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Gastrointestinal disorders Nausea	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	18.2% 2/11 • 6 months Other adverse events grade 2 or higher are reported.
Renal and urinary disorders Proteinuria	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	0.00% 0/11 • 6 months Other adverse events grade 2 or higher are reported.
General disorders Swollen feet	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	0.00% 0/11 • 6 months Other adverse events grade 2 or higher are reported.
Investigations Platelet count decreased	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	0.00% 0/11 • 6 months Other adverse events grade 2 or higher are reported.
Respiratory, thoracic and mediastinal disorders Upper respiratory symptoms	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	0.00% 0/11 • 6 months Other adverse events grade 2 or higher are reported.
Investigations Neutrophil count decreased	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	36.4% 4/11 • 6 months Other adverse events grade 2 or higher are reported.
Respiratory, thoracic and mediastinal disorders Mucositis	16.7% 1/6 • 6 months Other adverse events grade 2 or higher are reported.	0.00% 0/11 • 6 months Other adverse events grade 2 or higher are reported.
Investigations white blood cell decreased	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
General disorders Fatigue	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	18.2% 2/11 • 6 months Other adverse events grade 2 or higher are reported.
Metabolism and nutrition disorders Anorexia	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	18.2% 2/11 • 6 months Other adverse events grade 2 or higher are reported.
Psychiatric disorders Anxiety	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Psychiatric disorders Depression	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Gastrointestinal disorders Diarrhea	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	18.2% 2/11 • 6 months Other adverse events grade 2 or higher are reported.
Ear and labyrinth disorders Vertigo	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Infections and infestations urinary tract infection	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Nervous system disorders Headache	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Psychiatric disorders Insomnia	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Nervous system disorders Stroke	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Vascular disorders Thromboembolic event	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	18.2% 2/11 • 6 months Other adverse events grade 2 or higher are reported.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	18.2% 2/11 • 6 months Other adverse events grade 2 or higher are reported.
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	9.1% 1/11 • 6 months Other adverse events grade 2 or higher are reported.
Investigations Creatinine increased	0.00% 0/6 • 6 months Other adverse events grade 2 or higher are reported.	27.3% 3/11 • 6 months Other adverse events grade 2 or higher are reported.