Lung Cancer
Conditions
Keywords
stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as vinflunine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and help kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Giving vinflunine together with cetuximab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving vinflunine together with cetuximab works as second-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer.
Detailed description
OBJECTIVES: Primary * Estimate the objective response rate in patients receiving vinflunine and cetuximab as second-line therapy for stage IIIB or IV non-small cell lung cancer. Secondary * Determine the progression-free survival of patients treated with this regimen. * Determine the safety of this regimen in these patients. * Determine the overall survival of patients treated with this regimen. * Determine the duration of overall response in these patients. OUTLINE: This is a multicenter study. Patients receive vinflunine IV over 15-20 minutes on day 1 and cetuximab IV over 60-120 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may receive additional courses beyond 4 courses at the discretion of the principal investigator. After completion of study therapy, patients are followed periodically for 6 months.
Interventions
BIOLOGICALcetuximab
400 mg/m² week 1,then 250 mg/m² weekly
DRUGvinflunine
Vinflunine 320 mg/m² every 21 days
Sponsors
Bristol-Myers Squibb
UNC Lineberger Comprehensive Cancer Center
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
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) meeting 1 of the following criteria: * Unresectable stage IIIB disease with pleural effusion or pericardial effusion * Stage IIIB disease that was treated with chemotherapy alone as first-line therapy * Stage IV disease * Must have documented progression of disease after receiving one cytotoxic chemotherapy regimen for metastatic disease * At least one lesion that is bidimensionally measurable by CT scan or MRI * Must have evaluable disease outside the radiation field * New lesions that develop within the radiation field are allowed * Measurable disease status as defined by RECIST criteria * Brain metastases allowed provided they have been previously treated and are controlled PATIENT CHARACTERISTICS: Inclusion criteria: * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Absolute neutrophil count (ANC) \> 1,000/mm³ * Hemoglobin \> 8.0 g/dL * Platelet count \> 75,000/mm³ * Creatinine \< 2.0 times upper limit of normal (ULN) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 times ULN * Total bilirubin \< 2.5 times ULN * Prior malignancy allowed provided the patient's life expectancy is best defined by the diagnosis of NSCLC * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for up to 4 weeks after completion of study therapy
Exclusion criteria
* Peripheral neuropathy ≥ 2 * Severe allergic reaction to prior vinca alkaloid treatment * Active or uncontrolled infection * Significant history of uncontrolled cardiac disease, including any of the following: * Uncontrolled hypertension * Unstable angina * Myocardial infarction within the past 6 months * Uncontrolled congestive heart failure * Cardiomyopathy with decreased ejection fraction * Severe reaction to prior monoclonal antibody therapy PRIOR CONCURRENT THERAPY: Inclusion criteria: * See Disease Characteristics * Prior oral tyrosine kinase inhibitor therapy (e.g. gefitinib or erlotinib) allowed * Not considered cytotoxic therapy for study eligibility purposes if given alone as first-line therapy * At least 1 week since prior radiotherapy * At least 21 days since prior and no other concurrent chemotherapy * Prior adjuvant therapy allowed provided patient received one cytotoxic chemotherapy regimen as treatment for metastatic disease * Prior bevacizumab allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Tumor Response Rate as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Sum of Partial Responses (PR) and Complete Responses (CR). | Baseline, after cycle 2, within 2 weeks of completing cycle 4 | Per 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. Measurable lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 10mm with spiral CT scan or nonmeasurable, but evaluable. Evaluable is nonmeasurable disease that includes ascites, malignant pleural/pericardial effusion, bone lesions, or marrow involvement. |
Secondary
| Measure | Time frame |
|---|---|
| Duration of Response | After cycle 4 |
| Overall Survival | Every 30 days |
| Progression-free Survival | after cycle 2, within 2 weeks of completing cycle 4 |
Countries
United States
Participant flow
Pre-assignment details
18 patients were enrolled, 2 patients were consented but not enrolled. 1 patient withdrew and 1 patient was taken off the study due to decline in performance status.
Participants by arm
| Arm | Count |
|---|---|
| Vinflunine + Cetuximab Patients may receive more than 4 cycles of therapy if they continue to demonstrate response to therapy, have limited toxicity, and if the treating physician determines that they are deriving clinical benefit from the treatment. The decision of continuing therapy beyond 4 cycles must be discussed with the principal investigator.
cetuximab: 400 mg/m² week 1,then 250 mg/m² weekly
vinflunine: Vinflunine 320 mg/m² every 21 days | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
Baseline characteristics
| Characteristic | Vinflunine + Cetuximab |
|---|---|
| Age, Continuous | 60.5 years |
| Number of Participants who had a score of 0-1 in the The Eastern Cooperative Oncology Group (ECOG) | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 16 |
| other Total, other adverse events | 15 / 16 |
| serious Total, serious adverse events | 8 / 16 |
Outcome results
Primary
Overall Tumor Response Rate as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Sum of Partial Responses (PR) and Complete Responses (CR).
Per 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. Measurable lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 10mm with spiral CT scan or nonmeasurable, but evaluable. Evaluable is nonmeasurable disease that includes ascites, malignant pleural/pericardial effusion, bone lesions, or marrow involvement.
Time frame: Baseline, after cycle 2, within 2 weeks of completing cycle 4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vinflunine + Cetuximab | Overall Tumor Response Rate as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Sum of Partial Responses (PR) and Complete Responses (CR). | 3 Participants |
Secondary
Duration of Response
Time frame: After cycle 4
Population: Data not collected due to early study termination.
Secondary
Overall Survival
Time frame: Every 30 days
Population: Data not collected due to early study termination.
Secondary
Progression-free Survival
Time frame: after cycle 2, within 2 weeks of completing cycle 4
Population: Data not collected due to early study termination.