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

Phase II Trial of Bevacizumab in Combination With Gemcitabine and Carboplatin in Patients With Newly Diagnosed Non-Small Cell Lung Cancer (Excluding Squamous Cell Carcinoma)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00323869

Enrollment

Registered

2006-05-10

Start date

2006-06-30

Completion date

2013-10-31

Last updated

2016-09-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lung Cancer, Non-small Cell Lung Cancer (NSCLC)

Brief summary

A multi-center study of bevacizumab in combination with gemcitabine and carboplatin as treatment for newly-diagnosed advanced non-small cell lung cancer (NSCLC).

Detailed description

This is a open-label, phase 2, single-arm, multi-center study of bevacizumab combined with gemcitabine and carboplatin. This treatment is for newly-diagnosed advanced non-small cell lung cancer (NSCLC), excluding squamous cell carcinoma. All subjects will receive 15 mg/kg bevacizumab every 3 weeks cycle, 1000 mg/m² of gemcitabine on day 1 and 8 every 3 weeks cycle and carboplatin (AUC= 5 ) every 3 weeks. Carboplasm will be administered 1 hour prior to the gemcitabine infusion, bevacizumab will be administered 1 hour following chemotherapy infusion. Subjects will receive a maximum of 6 cycles of chemotherapy, but treatment with bevacizumab may continue as long as patients have no evidence of progressive disease and no significant treatment-related toxicities.

Interventions

DRUGBevacizumab

Murine humanized anti-vascular endothelial growth factor A (VEGF-A) monoclonal antibody

DRUGGemcitabine

Nucleoside analog

DRUGCarboplatin

Alkylating agent

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

: * Age 18 or higher * Life expectancy of at least 3 months * ECOG Performance status 0 to 1 * Advanced stage non-small cell lung cancer, NSCLC, Stage IIIB with malignant pleural effusion or Stage 4, excluding squamous cell histology, with measurable or evaluable disease * No prior systemic therapy for advanced NSCLC (prior therapy for early stage disease with one regimen is acceptable if it was completed at least 6 months prior to study entry) * Palliative radiotherapy to painful bony metastases is permitted prior to study entry if completed prior to initiation of study treatment, and there are no residual sequelae of therapy such as bone marrow suppression * Willingness to use appropriate contraception to avoid pregnancy during the study * Leukocytes ≥ 3,000/µL * Absolute neutrophil count ≥ 1,500/ µL * Platelets ≥ 100,000/ µL * Total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal * Creatinine: Within normal institutional limits * Creatinine clearance ≥ 60 mL/min/1.73 m² for patients with creatinine levels above institutional normal * Ability to sign informed consent

Exclusion criteria

* Prior systemic treatment for advanced NSCLC (one prior regimen of up to 4 cycles of neoadjuvant or adjuvant therapy for early stage disease will be allowed, if completed at least 6 months prior to study entry) * Known brain metastases * Prior treatment with bevacizumab * History of allergic reactions * Sensitivity attributed to compounds of similar chemical or biologic composition to bevacizumab * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in any other experimental drug study * Concomitant chemotherapy, radiotherapy, or investigational agents * Evidence of bleeding diathesis * Coagulopathy * Use of anti-coagulant agents including warfarin, heparin, aspirin, NSAIDs * Pregnant * Lactating * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study * Minor surgical procedures within 7 days prior to day 0 * Fine needle aspirations within 7 days prior to day 0 * Core biopsies within 7 days prior to day 0 * Urine protein: creatinine ratio ≥ 1.0 at screening * History of abdominal fistula within 6 months prior to Day 0 * Gastrointestinal perforation within 6 months prior to Day 0 * Intra-abdominal abscess within 6 months prior to Day 0 * Serious, non-healing wound * Ulcer * Bone fracture * Lung carcinoma of squamous cell histology * Any histology in close proximity to a major vessel * Significant cavitation as assessed by treating investigator in consultation with an attending radiologist * History of hemoptysis (bright red blood of 1/2 teaspoon or more) * Blood pressure of \> 150/100 mmHg * Unstable angina * New York Heart Association (NYHA) Grade 2 or greater congestive heart failure * History of myocardial infarction within 6 months * History of stroke within 6 months * Clinically significant peripheral vascular disease * Psychiatric illness/social situations that would limit compliance with study requirements * Another active malignancy except for non-melanoma skin cancers * Inability to comply with study and/or follow-up procedures

Design outcomes

Primary

Measure	Time frame	Description
Progression-free Survival (PFS)	18 months	Median progression-free survival (PFS) was assessed as the time to disease progression; toxicity requiring treatment discontinuation; or death.

Secondary

Measure	Time frame	Description
Overall Survival (OS)	36 months	To evaluate the safety of the combination regimen.
Partial Response (PR)	6 weeks	Number of subjects with PR per RECIST criteria
Complete Response (CR)	6 weeks	Number of subjects with CR per RECIST criteria
Response Rate (CR + PR + SD)	6 weeks	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.
Time-to-First Event	18 months	Median time-to-first event, with events defined as disease progression, death, or toxicity requiring drug discontinuation
Overall Survival (OS) at 12 Months	12 months	Number of subjects surviving 1 year after treatment initiation
Overall Survival (OS) at 24 Months	24 months	Number of subjects surviving 2 years after treatment initiation
Stable Disease (SD)	6 weeks	Number of subjects with SD per RECIST criteria

Countries

United States

Participant flow

Participants by arm

Arm	Count
Bevacizumab + Carboplatin + Gemcitabine 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)	47
Total	47

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	1

Baseline characteristics

Characteristic	Bevacizumab + Carboplatin + Gemcitabine
Age, Continuous	59 years
Eastern Cooperative Oncology Group (ECOG) performance status ECOG 0	3 participants
Eastern Cooperative Oncology Group (ECOG) performance status ECOG 1	44 participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants
Non-small Cell Lung Cancer (NSCLC) Histology Adenocarcinoma	30 participants
Non-small Cell Lung Cancer (NSCLC) Histology Bronchioloalveolar carcinoma (BAC)	4 participants
Non-small Cell Lung Cancer (NSCLC) Histology NSCLC not otherwise specified	13 participants
Non-small Cell Lung Cancer Stage NSCLC Stage III-B	8 participants
Non-small Cell Lung Cancer Stage NSCLC Stage IV	39 participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants
Race (NIH/OMB) Asian	10 Participants
Race (NIH/OMB) Black or African American	3 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants
Race (NIH/OMB) White	29 Participants
Sex: Female, Male Female	25 Participants
Sex: Female, Male Male	22 Participants
Smoking Status Currently a smoker	21 participants
Smoking Status Has stopped smoking (ex-smoker)	7 participants
Smoking Status Never a smoker	19 participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	17 / 47
serious Total, serious adverse events	28 / 47

Outcome results

Primary

Progression-free Survival (PFS)

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

Time frame: 18 months