Lung Cancer
Conditions
Keywords
recurrent non-small cell lung cancer, stage IV non-small cell lung cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with imatinib mesylate may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine together with imatinib mesylate works in treating patients with recurrent or metastatic non-small cell lung cancer.
Detailed description
OBJECTIVES: Primary * Evaluate the response rate in patients with recurrent or metastatic non-small cell lung cancer treated with gemcitabine hydrochloride and imatinib mesylate. Secondary * Assess time to progression in patients treated with this regimen. * Assess overall survival and 1-year survival of patients treated with this regimen. * Assess the toxicity of this regimen in these patients. OUTLINE: This is a multicenter, nonrandomized, uncontrolled, open-label study. Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.
Interventions
DRUGgemcitabine hydrochloride
1000 mg/m2 given intravenously at a FDR of 10 mg/m2/min on Days 3 and 10, every 21 days.
DRUGimatinib mesylate
400 mg/day orally, given Days 1-5 and 8-12 every 21 days
Sponsors
National Cancer Institute (NCI)
Novartis
Rutgers, The State University of New Jersey
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 confirmed non-small cell cancer * Recurrent disease after adjuvant treatment OR progressive disease after 1 prior treatment for recurrent or metastatic disease * Received at least 1 prior chemotherapy regimen and meets the following criteria: * No more than 1 prior chemotherapeutic regimen in the recurrent or metastatic setting * Patients who received prior chemotherapy in the adjuvant setting are eligible when 1 of the following criteria is met: * In first recurrence (after 1 prior regimen) * Received first-line chemotherapy in the recurrent setting after 2 prior regimens * Measurable disease * Must have ≥ 1 measurable target lesion outside prior radiotherapy field OR radiologic confirmation of disease progression within a prior radiotherapy field * No known or untreated brain metastases or carcinomatous meningitis * Clinically stable, treated brain metastases allowed provided it has been \> 7 days since prior steroids PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Life expectancy ≥ 3 months * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST and ALT ≤ 2.5 times ULN * Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study treatment * Able to swallow oral medication * No concurrent medical condition that would preclude study compliance * No history of allergic reaction to compounds of similar chemical or biological composition to gemcitabine hydrochloride or imatinib mesylate * No uncontrolled illness that would preclude study compliance, including any of the following: * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia requiring therapy * Myocardial infarction within the past 6 months * Active infection * No New York Heart Association class III-IV congestive heart failure * No chronic liver disease (i.e., chronic active hepatitis, cirrhosis) * No HIV positivity * No other primary malignancies within the past 5 years, except carcinoma in situ of the cervix or nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) * At least 3 weeks since prior anti-vascular endothelial growth factor therapy and recovered * At least 3 weeks since prior radiotherapy and recovered * More than 28 days since prior and no other concurrent investigational or commercial agents * More than 2 weeks since prior major surgery * No prior gemcitabine hydrochloride or imatinib mesylate for metastatic disease * No prior tyrosine kinase inhibitor, except for gefitinib or erlotinib hydrochloride * No concurrent therapeutic warfarin (prophylactic warfarin therapy ≤ 1 mg daily allowed) * No other concurrent medications that would preclude study compliance * No concurrent chronic systemic corticosteroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Meet Critieria for Response | 2 years | Response is considered Partial Response or Complete Response as 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, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | 2 years | — |
| 1-year Survival | 3 years | Accrual duration is 2 years with an additional year for assessment of 1-year survival. Outcome measure time frame is about 3 years. |
Countries
United States
Participant flow
Recruitment details
Seventeen patients were enrolled from April 2006 through October 2007 at Rutgers Cancer Institute of New Jersey, a comprehensive cancer cancert, and two of its affiliate hospitals within the CINJ Oncology Group.
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine Hydrochloride and Imatinib Mesylate gemcitabine hydrochloride : 1000 mg/m2 given intravenously at a FDR of 10 mg/m2/min on Days 3 and 10, every 21 days.
imatinib mesylate : 400 mg/day orally, given Days 1-5 and 8-12 every 21 days | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | Gemcitabine Hydrochloride and Imatinib Mesylate |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 59.5 years STANDARD_DEVIATION 8.5 |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 17 |
| serious Total, serious adverse events | 10 / 17 |
Outcome results
Primary
Percentage of Patients Who Meet Critieria for Response
Response is considered Partial Response or Complete Response as 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, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time frame: 2 years
Population: Fourteen subjects were evaluable for response. Three subjects were not assessed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine Hydrochloride and Imatinib Mesylate | Percentage of Patients Who Meet Critieria for Response | 0 percentage of patients who responded |
Secondary
1-year Survival
Accrual duration is 2 years with an additional year for assessment of 1-year survival. Outcome measure time frame is about 3 years.
Time frame: 3 years
Population: The study was closed early due to toxicity and insufficient data were collected to analyze this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine Hydrochloride and Imatinib Mesylate | 1-year Survival | 35 percentage of patients |
Secondary
Time to Progression
Time frame: 2 years
Population: The study was closed early due to toxicity and insufficient data were collected to analyze this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gemcitabine Hydrochloride and Imatinib Mesylate | Time to Progression | 2.77 months | Standard Deviation 2.07 |