Non-small Cell Lung Cancer
Conditions
Keywords
NSCLC, Abraxane, Carboplatin, Bevacizumab, Avastin
Brief summary
The purpose of this research study is to learn more about whether the combination of drugs carboplatin, Abraxane and Avastin helps treat non-small cell lung cancer (NSCLC). One of the standard treatments for advanced NSCLC is the combination of the drugs carboplatin, paclitaxel and Avastin. Paclitaxel can be associated with severe side effects that may make the treatment difficult to tolerate. Some of these side effects are caused by the solution used to dissolve paclitaxel before it can be administered. Abraxane is a different form of paclitaxel that does not need to be dissolved by this solution. Abraxane is approved for the treatment of breast cancer but is not approved to treat NSCLC. We will also be trying to learn more about how the drug Avastin may work to treat cancer.
Detailed description
* Participants will receive a single dose of Avastin 2 weeks before they are scheduled to start the combination of carboplatin, Abraxane and Avastin. Before the dose of Avastin is given, a perfusion CT scan and blood work will be performed. The perfusion CT scan and blood draw will be repeated 12 days after teh Avastin dose (2 days before beginning study treatment). * The combination of carboplatin, Abraxane and Avastin will be given in 3 week cycles and all drugs will be given as infusions. On day 1, Avastin, Abraxane and carboplatin wil be given. On Day 8 and 15, Abraxane will be given. Participants can receive up to 6 cycles of carboplatin, Abraxane and Avastin if their disease does not get worse and they do not experience intolerable side effects. * The following assessment procedures will be performed on day 1 of each cycle: physical exam; routine urine test (every other cycle); Performance status assessment. Routine blood tests will be performed on days 1, 8 and 15. * Additional procedures performed after cycles 2 and 4 and at 6 months after beginning study treatment are as follows: CT scan, PET scan, perfusion CT and blood work. * After 6 cycles of carboplatin, Abraxane and Avastin, participants will receive Avastin alone for three weeks. Participants can continue to receive Avastin as long as they do not experience unacceptable side effects.
Interventions
DRUGcarboplatin
Given by infusion on day 1 of each 3 week cycle for a maximum of 6 cycles
DRUGNab-paclitaxel
Given by infusion once weekly (days 1, 8 and 15) of each three week cycle for a maximum of 6 cycles
DRUGBevacizumab
IV infusion
Sponsors
Dana-Farber Cancer Institute
Celgene Corporation
Genentech, Inc.
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of non-small cell lung carcinoma of non-squamous histology * AJCC stage IIIB or Stage IV * Measurable disease by RECIST criteria, and must have at least one target lesion 1cm or greater in diameter for optimal perfusion CT scanning * No prior chemotherapy treatment or VEGF inhibitor treatment, although prior treatment with EGFR inhibitors will be allowed * 18 years of age or older * Adequate bone marrow, renal and liver function as outlined in the protocol
Exclusion criteria
* Life expectancy of less than 12 weeks * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study * Inadequately controlled hypertension * Any prior history of hypertensive crisis or hypertensive encephalopathy * NYHA Grade II or greater congestive heart failure * History of myocardial infarction or unstable angina within 6 months prior to study enrollment * History of stroke, transient ischemic attack within 6 months prior to study enrollment * Symptomatic CNS metastases or newly diagnosed CNS metastases that have not yet been definitively treated with radiation and/or surgery. Note that patients with a history of CNS metastases or cord compression are allowed if they have been definitively treated and are clinically stable. Maintenance steroids are allowed. Two weeks need to elapse from the completion of radiation, or 4 weeks from surgery, before starting avastin. Patients do have to remain clinically asymptomatic. * Significant vascular disease * Symptomatic peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major medical surgical procedure during the course of the study * Minor surgical procedure, excluding FNA, core biopsy or placement of a vascular access device, within 7 days prior to study enrollment * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment * Serious, non-healing wound, ulcer, or bone fracture * Proteinuria at screening * Pregnant or lactating * Lung carcinoma of squamous cell histology * History of hemoptysis within 3 months prior to study enrollment * Current, on-going treatment with full-dose warfarin or its equivalent at the onset of treatment * Current or recent (within 10 days of enrollment) use of aspirin or chronic use of other NSAIDs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6-month Progression Free Survival Rate | 6 Months | Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate to Carboplatin, Abraxane and Avastin | 3 years | Objective response rate to carboplatin, Abraxane and Avastin according to Response Evaluation Criteria in Solid Tumors \[Version 1.0\] |
| 6 Month Survival Rate | 6 months | The percentage of participants surviving at least six months after baseline |
| Overall Survival | 3 years | The median overall survival in months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy carboplatin: Given by infusion on day 1 of each 3 week cycle for a maximum of 6 cycles
Abraxane: Given by infusion once weekly (days 1, 8 and 15) of each three week cycle for a maximum of 6 cycles
Bevacizumab | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Chemotherapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants |
| Age, Continuous | 64 years |
| Region of Enrollment United States | 36 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 36 |
| other Total, other adverse events | 36 / 36 |
| serious Total, serious adverse events | 7 / 36 |
Outcome results
Primary
6-month Progression Free Survival Rate
Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: 6 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy | 6-month Progression Free Survival Rate | 74 percentage of participants |
Secondary
6 Month Survival Rate
The percentage of participants surviving at least six months after baseline
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy | 6 Month Survival Rate | 83 percentage of participants surviving |
Secondary
Objective Response Rate to Carboplatin, Abraxane and Avastin
Objective response rate to carboplatin, Abraxane and Avastin according to Response Evaluation Criteria in Solid Tumors \[Version 1.0\]
Time frame: 3 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chemotherapy | Objective Response Rate to Carboplatin, Abraxane and Avastin | Partial Response | 13 Participants |
| Chemotherapy | Objective Response Rate to Carboplatin, Abraxane and Avastin | Stable Disease | 13 Participants |
| Chemotherapy | Objective Response Rate to Carboplatin, Abraxane and Avastin | Progressive Disease | 2 Participants |
| Chemotherapy | Objective Response Rate to Carboplatin, Abraxane and Avastin | Not Evaluable for Response | 8 Participants |
Secondary
Overall Survival
The median overall survival in months
Time frame: 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy | Overall Survival | 13.7 Months |