Non-small Cell Lung Cancer
Conditions
Keywords
Lung cancer,, Non-small cell lung cancer, NSCLC, Metastatic, Gleevec, elderly
Brief summary
This study will evaluate the clinical efficacy of combining Gleevec (imatinib mesylate), a PDGFR antagonist, with front-line, single-agent paclitaxel in a cohort of elderly patients with advanced, non-small cell lung cancer.
Detailed description
Paclitaxel 90 mg/m2 IV on days 3, 10, 17 Imatinib 600 mg/day, oral administration in 4-day pulses bracketing each paclitaxel infusion (days 1-4; 8-11; 15-18) Cycle length: 28 days Number of cycles: up to 6
Interventions
DRUGImatinib mesylate
Imatinib (Gleevec) 600 mg/day, oral administration in 4-day pulses(days 1-4; 8-11; 15-18) Cycle length: 28 days Number of cycles: up to 6
DRUGPaclitaxel
Paclitaxel 90 mg/m2 IV on days 3, 10, 17 Cycle length: 28 days Number of cycles: up to 6
Sponsors
Fred Hutchinson Cancer Center
Novartis
New Mexico Cancer Research Alliance
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 70 years * Histologic or cytologic diagnosis of non-small cell lung cancer * At least one site of measurable disease, as defined by the modified RECIST criteria (See section 7.6) * Stage IIIB with pleural effusion or Stage IV disease. Includes patients who received surgery alone for early stage disease, now in relapse with advanced disease. Staging is according to the American Joint Committee on Cancer classification scheme, 6th edition.48 * Adequate hepatic, renal and marrow function * Liver function tests: total bilirubin \< 1.25 x upper limit of normal (ULN), AST and ALT \< 2.5 x ULN, Creatinine \< 1.5 x ULN * Baseline absolute neutrophil count \> 1500/μL * Baseline platelet count \> 100,000/μL * ECOG Performance Status 0, 1 or 2 at the time of informed consent. (See Appendix 1) * Written, voluntary consent * Patients with reproductive potential must use an acceptable contraceptive method. Such methods include: 1) Male hormonal contraception; 2) Partner without reproductive potential, including post-menopausal status or history of tubal ligation; 3) Partner with intrauterine device (IUD) or contraceptive vaginal ring; 4) Partner takes oral contraceptive pill, wears contraceptive patch, or has contraceptive implant; 5) Routine use of barrier method, such as condoms or diaphragm, during sexual intercourse.
Exclusion criteria
Uncontrolled brain metastasis. Patients with known brain metastasis must have completed treatment with surgery, radiation or both. In addition, they must be off corticosteroids. * Symptomatic neuropathy (Grade 2 or higher) * Prior chemotherapy for advanced non-small cell lung cancer. (Prior adjuvant, neoadjuvant, or chemoradiotherapy for NSCLC is permitted, provided at least 6 months elapsed prior to documented metastatic recurrence.) * Patient is \< 5 years free of another primary malignancy, except: a) if the other malignancy is basal cell carcinoma or cervical carcinoma in situ or b) if the other primary malignancy is not considered clinically significant and is requiring no active intervention * Prior radiation therapy to \> 25% of bone marrow * Grade III/IV congestive heart failure, as defined by NYHA criteria, or myocardial infarction within 6 months. * Any serious or uncontrolled concomitant disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study. * Patient has known chronic liver disease, e.g. diagnosis of chronic active hepatitis or cirrhosis. * Major surgery two weeks prior to study treatment * Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent * Any condition requiring continuous administration of systemic corticosteroids. * The patient is on therapeutic anti-coagulation with warfarin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 6 months | Response rates according to RECIST criteria (version 1.0) expressed as percentage of evaluable patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 12 Months | Overall survival as measured by the Kaplan-Meier method |
| Progression Free Survival | 12 months | Number of months post treatment without measurable progression according to RECIST criteria (version 1.0) |
| Toxicities | 12 months | Adverse events of grade 3 or higher, according to CTCAE version 3 |
Countries
United States
Participant flow
Recruitment details
Subject screening for this study began effective 08/12/2009 at the UNM Cancer Center. Recruitment was conducted through the outpatient clinic. Patients were recruited until 04/30/2010.
Participants by arm
| Arm | Count |
|---|---|
| Imatinib Mesylate and Paclitaxel Experimental: Treatment (enzyme inhibitor, chemotherapy) Patients receive paclitaxel IV on days 3, 10, and 17 and imatinib mesylate PO QD on days 1-4, 8-11, and 15-18. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | Imatinib Mesylate and Paclitaxel |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 34 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 74.5 years STANDARD_DEVIATION 4.6 |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 34 |
| serious Total, serious adverse events | 4 / 34 |
Outcome results
Primary
Response Rate
Response rates according to RECIST criteria (version 1.0) expressed as percentage of evaluable patients.
Time frame: 6 months
Population: 6 of the enrolled 34 patients were inevaluable for the primary endpoint of Response Rate due to withdrawal or death prior to first response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imatinib Mesylate and Paclitaxel | Response Rate | 32 Percentage of Participants |
Secondary
Overall Survival
Overall survival as measured by the Kaplan-Meier method
Time frame: 12 Months
Population: 6 of the enrolled 34 patients were inevaluable for the primary endpoint of Response Rate due to withdrawal or death prior to first response assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Imatinib Mesylate and Paclitaxel | Overall Survival | 7.3 Months |
Secondary
Progression Free Survival
Number of months post treatment without measurable progression according to RECIST criteria (version 1.0)
Time frame: 12 months
Population: 6 of the enrolled 34 patients were inevaluable for the primary endpoint of Response Rate due to withdrawal or death prior to first response assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Imatinib Mesylate and Paclitaxel | Progression Free Survival | 3.6 Months |
Secondary
Toxicities
Adverse events of grade 3 or higher, according to CTCAE version 3
Time frame: 12 months
Population: All enrolled and treated patients were evaluated for grade 3 or higher toxicities.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imatinib Mesylate and Paclitaxel | Toxicities | 34 Number of events |