Lung Cancer
Conditions
Keywords
stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer, squamous cell lung cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase II trial is studying how well paclitaxel albumin-stabilized nanoparticle formulation given together with carboplatin works in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer.
Detailed description
OBJECTIVES: Primary * To determine the response rate, in terms of overall response rate (complete response and partial response), of paclitaxel albumin-stabilized nanoparticle formulation and carboplatin in patients with stage IIIB-IV or recurrent non-small cell lung cancer who are ineligible for treatment with bevacizumab. Secondary * To evaluate safety of this regimen in these patients. * To describe the overall survival of these patients. * To describe progression-free survival of these patients. Tertiary Objectives * To explore, in a pilot fashion, the activity of this regimen using predictive biomarkers including serum SPARC levels, methylation of SPARC in primary tumor samples and serum, Ras mutations, ERCC1 and SPARC immunohistochemistry, and serum miRNA expression profiles. OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and carboplatin IV over 1-2 hours on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Paraffin-embedded tissue blocks or unstained slides and blood samples are collected for correlative studies. Samples are analyzed for serum SPARC by ELISA, Ras mutations, ERCC1 AND SPARC by immunohistochemistry, and serum miRNA expression profiling. After completion of study treatment, patients are followed periodically.
Interventions
DRUGcarboplatin
DRUGpaclitaxel albumin-stabilized nanoparticle formulation
GENETICprotein expression analysis
OTHERimmunoenzyme technique
OTHERimmunohistochemistry staining method
OTHERlaboratory biomarker analysis
Sponsors
National Comprehensive Cancer Network
Celgene Corporation
Greg Otterson
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed advanced non-small cell lung cancer (NSCLC) meeting 1 of the following criteria: * Stage IIIB disease with malignant pleural effusion * Stage IV disease * Recurrent disease * Squamous cell histology allowed * Not eligible for curative treatment or treatment with bevacizumab * Measurable disease according to RECIST * Tumor (paraffin blocks or slides) must be available for correlative biomarker studies * No uncontrolled brain metastases (or leptomeningeal disease) * Controlled brain metastases allowed * Able to receive appropriate therapeutic radiotherapy * Able to taper off all steroids without symptoms suggestive of increased intracranial pressure (nausea, vomiting, focal neurologic symptoms) for at least 7 days PATIENT CHARACTERISTICS: * ECOG (Eastern Cooperative Oncology Group) performance status 0-2 * ANC (absolute neutrophil count) ≥ 1.5 x 10\^9/L * Platelets ≥ 100 x 10\^9/L * Hemoglobin ≥ 9.0 g/L * Total bilirubin ≤ 1.5 mg/dL * AST (aspartate aminotransferase) and ALT (alanine aminotransferase) \< 2.5 times upper limit of normal * Creatinine ≤ 1.5 mg/dL OR creatinine clearance \> 50 mg/mL * No known HIV or hepatitis B or C * Not pregnant * Negative pregnancy test * Thrombotic or embolic event within the past 6 months allowed, provided adequately controlled with therapeutic anticoagulation * Hemoptysis allowed, provided it is not life threatening or requires palliative procedures (e.g., endobronchial therapy or radiotherapy) * No cardiac disease, including any of the following: * NYHA (New York Heart Association) class III-IV congestive heart failure * Unstable angina (angina symptoms at rest) * New onset angina (began within the past 3 months) * Myocardial infarction within the past 6 months * No uncontrolled hypertension, defined as systolic blood pressure (BP) \> 150 mm Hg or diastolic BP \> 90 mm Hg despite optimal medical management * No peripheral neuropathy ≥ grade 2 * No active clinically serious infection \> CTCAE grade 2 * No serious non-healing wound, ulcer, or bone fracture * No significant traumatic injury within the past 4 weeks * No evidence or history of bleeding diathesis or coagulopathy * No prior malignancy, except for adequately treated basal cell skin cancer, carcinoma in situ of the cervix, or other cancer for which the patient has been disease-free for 2 years * Stage I (T1c) prostate cancer adequately treated 2 years prior to diagnosis of NSCLC allowed, however metastatic prostate cancer currently receiving hormonal therapy or chemotherapy is not allowed * No significant psychiatric illness, in the opinion of the principal investigator, that would prevent adequate informed consent or render therapy unsafe PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Concurrent therapeutic anticoagulation, \> 325 mg acetylsalicylic acid, or chronic non-steroid anti-inflammatory drug use allowed * At least 14 days since prior and no concurrent radiotherapy * More than 4 weeks since prior major surgery or open biopsy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate Defined as Complete or Partial Response as Assessed by RECIST Version 1.0 Criteria. | Up to 5 years | Response rate is overall response rate (CR+PR) as defined by RECIST criteriaPer 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Up to 5 years | 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 |
| Overall Survival | Up to 5 years | Will be analyzed using a Kaplan-Meier methods. |
| Incidence and Intensity of Adverse Events Graded According to NCI CTCAE v. 3.0 | Up to 5 years | The incidence and intensity of adverse events graded according to NCI CTCAE v. 3.0 will be evaluated using descriptive statistics |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled in the trial between September 2008 and December 2011.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Nab-paclitaxel, Carboplatin) Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and carboplatin IV over 1-2 hours on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
carboplatin
paclitaxel albumin-stabilized nanoparticle formulation
protein expression analysis
immunoenzyme technique
immunohistochemistry staining method
laboratory biomarker analysis | 63 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Non evaluable for response | 10 |
Baseline characteristics
| Characteristic | Treatment (Nab-paclitaxel, Carboplatin) |
|---|---|
| Age, Continuous | 63.3 years |
| Region of Enrollment United States | 63 patients |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 63 / 63 |
| serious Total, serious adverse events | 2 / 63 |
Outcome results
Primary
Overall Response Rate Defined as Complete or Partial Response as Assessed by RECIST Version 1.0 Criteria.
Response rate is overall response rate (CR+PR) as defined by RECIST criteriaPer 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.
Time frame: Up to 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Nab-paclitaxel, Carboplatin) | Overall Response Rate Defined as Complete or Partial Response as Assessed by RECIST Version 1.0 Criteria. | Partial Response | 38.1 percentage of patients |
| Treatment (Nab-paclitaxel, Carboplatin) | Overall Response Rate Defined as Complete or Partial Response as Assessed by RECIST Version 1.0 Criteria. | Complete Response | 0 percentage of patients |
Secondary
Incidence and Intensity of Adverse Events Graded According to NCI CTCAE v. 3.0
The incidence and intensity of adverse events graded according to NCI CTCAE v. 3.0 will be evaluated using descriptive statistics
Time frame: Up to 5 years
Population: Grade 3 and 4
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Nab-paclitaxel, Carboplatin) | Incidence and Intensity of Adverse Events Graded According to NCI CTCAE v. 3.0 | Neutropenia | 12 patients |
| Treatment (Nab-paclitaxel, Carboplatin) | Incidence and Intensity of Adverse Events Graded According to NCI CTCAE v. 3.0 | Thrombocytopenia | 7 patients |
| Treatment (Nab-paclitaxel, Carboplatin) | Incidence and Intensity of Adverse Events Graded According to NCI CTCAE v. 3.0 | Leukopenia/lymphopenia | 13 patients |
| Treatment (Nab-paclitaxel, Carboplatin) | Incidence and Intensity of Adverse Events Graded According to NCI CTCAE v. 3.0 | Sensory neuropathy | 19 patients |
| Treatment (Nab-paclitaxel, Carboplatin) | Incidence and Intensity of Adverse Events Graded According to NCI CTCAE v. 3.0 | Anemia | 7 patients |
| Treatment (Nab-paclitaxel, Carboplatin) | Incidence and Intensity of Adverse Events Graded According to NCI CTCAE v. 3.0 | Fatigue | 14 patients |
Secondary
Overall Survival
Will be analyzed using a Kaplan-Meier methods.
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Nab-paclitaxel, Carboplatin) | Overall Survival | 9.7 months |
Secondary
Progression Free Survival
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: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Nab-paclitaxel, Carboplatin) | Progression Free Survival | 5.0 months |