Trial Outcomes & Findings for Phase II Bevacizumab, Gemcitabine and Carboplatin in Newly Diagnosed Non-Small Cell Lung Cancer (NCT NCT00323869)

NCT ID: NCT00323869

Last Updated: 2016-09-07

Results Overview

Median progression-free survival (PFS) was assessed as the time to disease progression; toxicity requiring treatment discontinuation; or death.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 48 participants
• Primary outcome timeframe: 18 months
• Results posted on: 2016-09-07

Participant Flow

Participant milestones

Measure	Bevacizumab + Carboplatin + Gemcitabine Bevacizumab in combination with carboplatin and gemcitabine Bevacizumab was administered 15 mg/kg IV on day 1 of each 3-week cycle (once per cycle) for up to 6 cycles in combination with chemotherapy, then continuing until evidence of progressive disease or significant treatment-related toxicity Gemcitabine, administered 1000 mg/m2 IV on days 1 and 8 of each 3-week cycle (twice per cycle) for up to 6 cycles Carboplatin, administered IV at area under the curve (AUC) of 5, every 3 weeks on day 1 of each 3-week cycle (once per cycle) for up to 6 cycles Carboplatin was administered before gemcitabine infusion. Bevacizumab was administered 1 hour after end of all chemotherapy infusions. Bevacizumab: Murine humanized anti-vascular endothelial growth factor A (VEGF-A) monoclonal antibody Gemcitabine: Nucleoside analog Carboplatin: Alkylating agent
Overall Study STARTED	48
Overall Study Treatment Initiation	47
Overall Study COMPLETED	47
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

Bevacizumab + Carboplatin + Gemcitabine Bevacizumab in combination with carboplatin and gemcitabine Bevacizumab was administered 15 mg/kg IV on day 1 of each 3-week cycle (once per cycle) for up to 6 cycles in combination with chemotherapy, then continuing until evidence of progressive disease or significant treatment-related toxicity Gemcitabine, administered 1000 mg/m2 IV on days 1 and 8 of each 3-week cycle (twice per cycle) for up to 6 cycles Carboplatin, administered IV at area under the curve (AUC) of 5, every 3 weeks on day 1 of each 3-week cycle (once per cycle) for up to 6 cycles Carboplatin was administered before gemcitabine infusion. Bevacizumab was administered 1 hour after end of all chemotherapy infusions. Bevacizumab: Murine humanized anti-vascular endothelial growth factor A (VEGF-A) monoclonal antibody Gemcitabine: Nucleoside analog Carboplatin: Alkylating agent

Overall Study Death

1

Baseline Characteristics

Phase II Bevacizumab, Gemcitabine and Carboplatin in Newly Diagnosed Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Bevacizumab + Carboplatin + Gemcitabine n=47 Participants Treatment provided in 3-week cycles: * 15 mg/kg bevacizumab Day 1 of each cycle * 1000 mg/m2 gemcitabine Days 1 and 8 of each cycle * Carboplatin (AUC of 5 every 3 weeks)
Age, Continuous	59 years n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) performance status ECOG 0	3 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) performance status ECOG 1	44 participants n=5 Participants
Smoking Status Never a smoker	19 participants n=5 Participants
Smoking Status Has stopped smoking (ex-smoker)	7 participants n=5 Participants
Smoking Status Currently a smoker	21 participants n=5 Participants
Non-small Cell Lung Cancer (NSCLC) Histology Adenocarcinoma	30 participants n=5 Participants
Non-small Cell Lung Cancer (NSCLC) Histology Bronchioloalveolar carcinoma (BAC)	4 participants n=5 Participants
Non-small Cell Lung Cancer (NSCLC) Histology NSCLC not otherwise specified	13 participants n=5 Participants
Non-small Cell Lung Cancer Stage NSCLC Stage III-B	8 participants n=5 Participants
Non-small Cell Lung Cancer Stage NSCLC Stage IV	39 participants n=5 Participants

PRIMARY outcome

Timeframe: 18 months

Population: Includes all subjects who initiated treatment

Median progression-free survival (PFS) was assessed as the time to disease progression; toxicity requiring treatment discontinuation; or death.

Outcome measures

Measure	Bevacizumab + Carboplatin + Gemcitabine n=47 Participants Treatment provided in 3-week cycles: * 15 mg/kg bevacizumab Day 1 of each cycle * 1000 mg/m2 gemcitabine Days 1 and 8 of each cycle * Carboplatin (AUC of 5 every 3 weeks)
Progression-free Survival (PFS)	8.7 months Interval 7.8 to 17.9

SECONDARY outcome

Timeframe: 6 weeks

Population: Includes all subjects who initiated treatment

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions, by computed tomography (CT); bone scan; positron emission tomography (PET) scan; and/or magnetic resonance imaging (MRI) as necessary to assess diseasE

Response determined as the number of subjects with any clinical response (CR + PR + SD) per RECIST criteria.

• Complete Response (CR) = disappearance of all target lesions
• Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions
• Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, or appearance of new cancer lesions
• Stable Disease (SD): No significant effect, does not meet criteria for PR or PD.

Outcome measures

Measure	Bevacizumab + Carboplatin + Gemcitabine n=47 Participants Treatment provided in 3-week cycles: * 15 mg/kg bevacizumab Day 1 of each cycle * 1000 mg/m2 gemcitabine Days 1 and 8 of each cycle * Carboplatin (AUC of 5 every 3 weeks)
Response Rate (CR + PR + SD)	41 participants

SECONDARY outcome

Timeframe: 36 months

Population: Includes all subjects who initiated treatment

To evaluate the safety of the combination regimen.

Outcome measures

Measure	Bevacizumab + Carboplatin + Gemcitabine n=47 Participants Treatment provided in 3-week cycles: * 15 mg/kg bevacizumab Day 1 of each cycle * 1000 mg/m2 gemcitabine Days 1 and 8 of each cycle * Carboplatin (AUC of 5 every 3 weeks)
Overall Survival (OS)	12.8 months Interval 10.0 to 16.5

SECONDARY outcome

Timeframe: 6 weeks

Population: Includes all subjects who initiated treatment

Number of subjects with PR per RECIST criteria

Outcome measures

Measure	Bevacizumab + Carboplatin + Gemcitabine n=47 Participants Treatment provided in 3-week cycles: * 15 mg/kg bevacizumab Day 1 of each cycle * 1000 mg/m2 gemcitabine Days 1 and 8 of each cycle * Carboplatin (AUC of 5 every 3 weeks)
Partial Response (PR)	7 participants

SECONDARY outcome

Timeframe: 6 weeks

Population: Includes all subjects who initiated treatment

Number of subjects with CR per RECIST criteria

Outcome measures

Measure	Bevacizumab + Carboplatin + Gemcitabine n=47 Participants Treatment provided in 3-week cycles: * 15 mg/kg bevacizumab Day 1 of each cycle * 1000 mg/m2 gemcitabine Days 1 and 8 of each cycle * Carboplatin (AUC of 5 every 3 weeks)
Complete Response (CR)	0 participants

SECONDARY outcome

Timeframe: 6 weeks

Population: Includes all subjects who initiated treatment

Number of subjects with SD per RECIST criteria

Outcome measures

Measure	Bevacizumab + Carboplatin + Gemcitabine n=47 Participants Treatment provided in 3-week cycles: * 15 mg/kg bevacizumab Day 1 of each cycle * 1000 mg/m2 gemcitabine Days 1 and 8 of each cycle * Carboplatin (AUC of 5 every 3 weeks)
Stable Disease (SD)	34 participants

SECONDARY outcome

Timeframe: 18 months

Population: Includes all subjects who initiated treatment

Median time-to-first event, with events defined as disease progression, death, or toxicity requiring drug discontinuation

Outcome measures

Measure	Bevacizumab + Carboplatin + Gemcitabine n=47 Participants Treatment provided in 3-week cycles: * 15 mg/kg bevacizumab Day 1 of each cycle * 1000 mg/m2 gemcitabine Days 1 and 8 of each cycle * Carboplatin (AUC of 5 every 3 weeks)
Time-to-First Event	6.4 months Interval 4.8 to 7.9

SECONDARY outcome

Timeframe: 12 months

Population: Includes all subjects who initiated treatment

Number of subjects surviving 1 year after treatment initiation

Outcome measures

Measure	Bevacizumab + Carboplatin + Gemcitabine n=47 Participants Treatment provided in 3-week cycles: * 15 mg/kg bevacizumab Day 1 of each cycle * 1000 mg/m2 gemcitabine Days 1 and 8 of each cycle * Carboplatin (AUC of 5 every 3 weeks)
Overall Survival (OS) at 12 Months	27 participants

SECONDARY outcome

Timeframe: 24 months

Population: Includes all subjects who initiated treatment

Number of subjects surviving 2 years after treatment initiation

Outcome measures

Measure	Bevacizumab + Carboplatin + Gemcitabine n=47 Participants Treatment provided in 3-week cycles: * 15 mg/kg bevacizumab Day 1 of each cycle * 1000 mg/m2 gemcitabine Days 1 and 8 of each cycle * Carboplatin (AUC of 5 every 3 weeks)
Overall Survival (OS) at 24 Months	5 participants

Adverse Events

Bevacizumab + Carboplatin + Gemcitabine

Serious events: 28 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bevacizumab + Carboplatin + Gemcitabine n=47 participants at risk Treatment provided in 3-week cycles: * 15 mg/kg bevacizumab Day 1 of each cycle * 1000 mg/m2 gemcitabine Days 1 and 8 of each cycle * Carboplatin (AUC of 5 every 3 weeks)
Blood and lymphatic system disorders Anemia	4.3% 2/47 • Number of events 2 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Blood and lymphatic system disorders Neutropenia	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Nervous system disorders Confusion	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Respiratory, thoracic and mediastinal disorders Pneumonia	4.3% 2/47 • Number of events 2 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Blood and lymphatic system disorders Thrombocytopenia	8.5% 4/47 • Number of events 4 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Respiratory, thoracic and mediastinal disorders Hemoptysis	4.3% 2/47 • Number of events 2 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
General disorders Death	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Respiratory, thoracic and mediastinal disorders Dyspnea	6.4% 3/47 • Number of events 3 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Blood and lymphatic system disorders Hemorrahage	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Blood and lymphatic system disorders Platetes	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Blood and lymphatic system disorders Hypotension	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Blood and lymphatic system disorders Leukocytes	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Metabolism and nutrition disorders Hyponatreamia due to SIADH	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
General disorders Pain	6.4% 3/47 • Number of events 3 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Respiratory, thoracic and mediastinal disorders Cough	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Metabolism and nutrition disorders Bilirubin	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Blood and lymphatic system disorders Hematoma	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary Respiratory Distress	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks

Other adverse events

Measure	Bevacizumab + Carboplatin + Gemcitabine n=47 participants at risk Treatment provided in 3-week cycles: * 15 mg/kg bevacizumab Day 1 of each cycle * 1000 mg/m2 gemcitabine Days 1 and 8 of each cycle * Carboplatin (AUC of 5 every 3 weeks)
Blood and lymphatic system disorders Neutropenia	8.5% 4/47 • Number of events 6 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Blood and lymphatic system disorders Thrombocytopenia	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Blood and lymphatic system disorders Anemia	4.3% 2/47 • Number of events 2 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Nervous system disorders Confusion	4.3% 2/47 • Number of events 2 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Blood and lymphatic system disorders Leukocytes	6.4% 3/47 • Number of events 3 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Metabolism and nutrition disorders Transaminitis	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Cardiac disorders Pain	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Blood and lymphatic system disorders Neutrophilis/Granolocytes	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Infections and infestations Infection	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks
Blood and lymphatic system disorders Creatinine	2.1% 1/47 • Number of events 1 • 6 weeks All assessments were taken after every two cycles. Evaluations were taken the first 6 weeks, then every 3 weeks

Additional Information

Heather A Wakelee, MD, Associate Professor of Medicine (Oncology)

Stanford University Medical Center

Phone: 650-498-6000

Email: hwakelee@stanford.edu

Results disclosure agreements

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