Malignant Pleural Effusion, Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
Conditions
Brief summary
This phase II trial is studying how well giving imatinib mesylate together with paclitaxel works in treating older patients with stage IIIB or stage IV non-small cell lung cancer. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imatinib mesylate together with paclitaxel may kill more tumor cells
Detailed description
PRIMARY OBJECTIVES: I. To estimate the clinical efficacy of the combination of weekly paclitaxel and intermittent imatinib in elderly patients with advanced non-small cell lung cancer. SECONDARY OBJECTIVES: I. To evaluate the safety profile of the combination of weekly paclitaxel and intermittent imatinib in elderly patients with advanced non-small cell lung cancer. II. To collect paraffin tissue blocks for a companion project evaluating the expression of platelet derived growth factor (PDGF) by original tumor specimens, and its relationship to response rate and survival. OUTLINE: Patients receive paclitaxel intravenously (IV) on days 3, 10, and 17 and imatinib mesylate orally (PO) once daily (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. After completion of study treatment, patients are followed up periodically.
Interventions
DRUGimatinib mesylate
Given PO
DRUGpaclitaxel
Given IV
Sponsors
National Cancer Institute (NCI)
University of Washington
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
* Histologic or cytologic diagnosis of non-small cell lung cancer * At least one site of measurable disease, as defined by the modified RECIST criteria * 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 * Total bilirubin \< 1.25 x upper limit of normal (ULN) * Baseline absolute neutrophil count \>= 1500/uL * Baseline platelet count \>= 100,000/uL * ECOG Performance Status 0, 1 or 2 at the time of informed consent * 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 * AST and ALT =\< 2.5 x ULN * Creatinine =\< 1.5 x ULN
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 * The administration of any other anticancer agents including chemotherapy and biologic agents is NOT permitted * The use of other concurrent investigational drugs is not allowed * Participants in this study must avoid grapefruit juice or other grapefruit-containing products for the duration of treatment with imatinib
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (Complete and Partial Responses) as Assessed by RECIST Criteria | Baseline, Week 4 of courses 2, 4 and 6 | 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; Overall Response (OR) = CR + PR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Tumor Progression | Baseline and every 2 months post treatment until the date of first documented tumor progression or date of death from any cause, whichever came first, assessed 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 | Every 3 months for 5 years | — |
Countries
United States
Participant flow
Recruitment details
Patients that were aged 70 years and above that had never received treatment for metastatic NSCLC were approached for study participation.
Participants by arm
| Arm | Count |
|---|---|
| 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.
imatinib mesylate: Given PO
paclitaxel: Given IV
immunohistochemistry staining method: Optional correlative studies | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | Treatment (Enzyme Inhibitor, Chemotherapy) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 34 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 75 years |
| 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 | 26 / 34 |
| serious Total, serious adverse events | 14 / 34 |
Outcome results
Primary
Overall Response Rate (Complete and Partial Responses) as Assessed by RECIST Criteria
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; Overall Response (OR) = CR + PR
Time frame: Baseline, Week 4 of courses 2, 4 and 6
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Enzyme Inhibitor, Chemotherapy) | Overall Response Rate (Complete and Partial Responses) as Assessed by RECIST Criteria | 11 Participants |
Secondary
Overall Survival
Time frame: Every 3 months for 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Enzyme Inhibitor, Chemotherapy) | Overall Survival | 7.3 months |
Secondary
Time to Tumor Progression
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: Baseline and every 2 months post treatment until the date of first documented tumor progression or date of death from any cause, whichever came first, assessed up to 5 years.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Enzyme Inhibitor, Chemotherapy) | Time to Tumor Progression | 3.6 months |