Lung Cancer
Conditions
Keywords
bronchoalveolar cell lung cancer, 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 pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well pemetrexed disodium works in treating patients with stage III or stage IV non-small cell lung cancer.
Detailed description
OBJECTIVES: Primary * Assess overall survival of patients with selected stage IIIB or IV bronchoalveolar carcinoma treated with pemetrexed disodium. Secondary * Evaluate the progression-free survival of patients treated with this drug. * Evaluate the response rate (confirmed and unconfirmed, partial and complete) in the subset of patients with measurable disease treated with this drug using standard RECIST criteria and computer assisted image analysis. * Evaluate frequency and severity of toxicities in patients treated with this drug. * Perform molecular correlative studies on patient tissue to investigate potential predictors of efficacy. (This will not be completed as this study was closed due to poor accrual.) OUTLINE: Patients are stratified according to prior treatment with gefitinib or erlotinib (yes vs no). Patients receive pemetrexed disodium intravenous (IV) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 3 years. PROJECTED ACCRUAL: A total of 99 patients will be accrued for this study.
Interventions
DRUGpemetrexed
Pemetrexed 500 mg/m\^2 intravenous (IV) over 10 min every 21 days until any of the following criteria is met: (1) Progression of disease or symptomatic deterioration; (2) Unacceptable toxicity; (3) Treatment delay ≥ 3 weeks, for any reason; (4) The patient may withdraw from the study at any time for any reason; (5) Physician's discretion.
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
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 bronchoalveolar carcinoma (BAC) or BAC variants such as adenocarcinoma with BAC features or BAC with invasive adenocarcinoma * Cytology specimens, such as bronchial brushings, washings, or fine needle aspiration specimens alone are not acceptable for diagnosis * Stage IV disease OR selected stage IIIB (T4 \[secondary to malignant pleural effusion only\], any N, M0) disease * Incompletely resected or unresectable disease * Pleural effusions, ascites, or laboratory parameters cannot be only evidence of disease * Measurable disease or nonmeasurable disease documented by CT scan * No known brain metastases PATIENT CHARACTERISTICS: * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * SGOT and SGPT ≤ 2.5 times ULN ( ≤ 5 times ULN if due to liver metastases) * Alkaline phosphatase ≤ 2.5 times ULN ( ≤ 5 times ULN if due to bone metastases) * Creatinine clearance ≥ 45 mL/min OR creatinine ≤ 1.5 times ULN * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 75,000/mm³ * Zubrod 0-2 * No history of allergic reaction to compounds of similar chemical or biological composition as pemetrexed disodium * Must provide smoking history * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission * Not pregnant or nursing * Fertile patients must use effective contraception * Able to swallow pills PRIOR CONCURRENT THERAPY: * No more than 2 prior systemic therapies (including epidermal growth factor receptor inhibitor) * At least 28 days since prior systemic therapy * Patients treated with prior erlotinib or gefitinib must have shown progression since treatment * No prior pemetrexed disodium * At least 28 days since prior radiotherapy and recovered * Must have measurable or nonmeasurable disease outside previously irradiated area or a new lesion within previously irradiated area * At least 14 days since prior palliative radiotherapy and recovered * At least 28 days since prior thoracic or major surgery and recovered * No concurrent surgery * No other concurrent therapy (hormonal, biologic or radiotherapy) for this disease * No concurrent antiretroviral therapy * Patients should discontinue non-steroidal anti-inflammatory drugs (NSAIDs) with longer half lives (etodolac, ketordac, sulindac, naproxen, naproxen sodium, oxaprozin, nabumetone, diflunisal, salsalate, celecoxib, rofecoxib, valdecoxib, meloxicam, piroxicam) at least 5 days before and for 2 days following pemetrexed treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 0 - 3 years | Measured from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 0 - 3 years | Progression is defined as any one or more of the following: 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline; Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided); Appearance of any new lesion/site; Death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is defined as globabl deterioration of health status requiring discontinuation of treatment without objective evidence of progression. Progression-free survival is measured from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact. |
| Response (Confirmed and Unconfirmed, Complete and Partial) | Assessed at weeks 7 and 13 while on treatment. After off treatment prior to disease progression, disease assessment takes place every 3 months for a maximum of 3 years. | Complete response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Normalization of markers and other abnormal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration. |
| Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Patients were assessed for adverse events 4 weeks after starting treatment. Assessments for adverse events continued after every cycle of treatment (every 3 weeks) for the duration of protocol treatment. | Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed Pemetrexed Disodium 500 mg/m\^2 intravenous (IV) over 10 min every 21 days until any of the following criteria is met: (1) Progression of disease or symptomatic deterioration; (2) Unacceptable toxicity; (3) Treatment delay ≥ 3 weeks, for any reason; (4) The patient may withdraw from the study at any time for any reason; (5) Physician's discretion. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Did not receive protocol treatment | 2 |
| Overall Study | Ineligible | 1 |
| Overall Study | Not protocol specified | 2 |
| Overall Study | Progression/Relapse | 15 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Pemetrexed |
|---|---|
| Age Continuous | 68.2 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Histology Adenocarcinoma w/BAC features | 18 participants |
| Histology Bronchioloalveolar | 6 participants |
| Number of Metastatic Sites Multiple | 7 participants |
| Number of Metastatic Sites None | 5 participants |
| Number of Metastatic Sites Single | 12 participants |
| Prior EGFR-TKI Therapy No | 19 participants |
| Prior EGFR-TKI Therapy Yes | 5 participants |
| Prior Radiation Therapy No | 21 participants |
| Prior Radiation Therapy Yes | 3 participants |
| Prior Surgery No | 13 participants |
| Prior Surgery Yes | 11 participants |
| Prior Systemic Treatment No | 14 participants |
| Prior Systemic Treatment Yes | 10 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 12 Participants |
| Smoking Status Current | 5 participants |
| Smoking Status Former | 16 participants |
| Smoking Status Never | 3 participants |
| Stage IIIB | 0 participants |
| Stage IV | 24 participants |
| Weight Loss Last 6 months 10% to 20% | 1 participants |
| Weight Loss Last 6 months > 20% | 0 participants |
| Weight Loss Last 6 months < 5% | 20 participants |
| Weight Loss Last 6 months 5% to < 10% | 3 participants |
| Zubbrod Performance Status 0 | 12 participants |
| Zubbrod Performance Status 1 | 12 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
Overall Survival
Measured from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time frame: 0 - 3 years
Population: Eligible and analyzable patients were included in this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Premetrexed | Overall Survival | 25 months |
Secondary
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Time frame: Patients were assessed for adverse events 4 weeks after starting treatment. Assessments for adverse events continued after every cycle of treatment (every 3 weeks) for the duration of protocol treatment.
Population: Eligible patients who received any treatment were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | ALT, SGPT (serum glutamic pyruvic transaminase) | 1 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | AST, SGOT | 1 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Diarrhea | 1 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Dyspnea (shortness of breath) | 1 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Fatigue (asthenia, lethargy, malaise) | 3 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Febrile neutropenia | 1 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Glucose, serum-high (hyperglycemia) | 3 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Hemoglobin | 2 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Skin | 1 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus | 1 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Leukocytes (total WBC) | 2 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Lymphopenia | 1 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Neutrophils/granulocytes (ANC/AGC) | 3 Participants |
| Premetrexed | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Platelets | 2 Participants |
Secondary
Progression-free Survival
Progression is defined as any one or more of the following: 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline; Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided); Appearance of any new lesion/site; Death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is defined as globabl deterioration of health status requiring discontinuation of treatment without objective evidence of progression. Progression-free survival is measured from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.
Time frame: 0 - 3 years
Population: Eligible and analyzable patients were included in this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Premetrexed | Progression-free Survival | 6 months |
Secondary
Response (Confirmed and Unconfirmed, Complete and Partial)
Complete response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Normalization of markers and other abnormal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration.
Time frame: Assessed at weeks 7 and 13 while on treatment. After off treatment prior to disease progression, disease assessment takes place every 3 months for a maximum of 3 years.
Population: Eligible and analyzable patients with measurable disease at baseline are included in this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Premetrexed | Response (Confirmed and Unconfirmed, Complete and Partial) | 29 percentage of participants |