Clinical trial NCT00323869: Phase II Bevacizumab, Gemcitabine and Carboplatin in Newly Diagnosed Non-Small Cell Lung Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Non-small Cell Lung Cancer (NSCLC)
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
name: Genentech, Inc.
First posted: 2006-05-10
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: 18 months
Secondary outcomes:
measure: Response Rate (CR + PR + SD)
timeFrame: 6 weeks
measure: Overall Survival (OS)
timeFrame: 36 months
measure: Partial Response (PR)
timeFrame: 6 weeks
measure: Complete Response (CR)
timeFrame: 6 weeks
measure: Stable Disease (SD)
timeFrame: 6 weeks
measure: Time-to-First Event
timeFrame: 18 months
measure: Overall Survival (OS) at 12 Months
timeFrame: 12 months
measure: Overall Survival (OS) at 24 Months
timeFrame: 24 months
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: VA Palo Alto Healthcare System
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Heather A Wakelee, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clement-Duchene C, Krupitskaya Y, Ganjoo K, Lavori P, McMillan A, Kumar A, Zhao G, Padda S, Zhou L, Pedro-Salcedo MS, Colevas AD, Wakelee HA. A phase II first-line study of gemcitabine, carboplatin, and bevacizumab in advanced stage nonsquamous non-small cell lung cancer. J Thorac Oncol. 2010 Nov;5(11):1821-5. doi: 10.1097/JTO.0b013e3181f1d23c.