Lung Cancer
Conditions
Keywords
recurrent small cell lung cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Some tumors become resistant to chemotherapy drugs. Giving interferon alfa and isotretinoin together with paclitaxel may reduce resistance to the drug and allow the tumor cells to be killed. PURPOSE: This phase II trial is studying how well giving interferon alfa and isotretinoin together with paclitaxel works in treating patients with recurrent small cell lung cancer.
Detailed description
OBJECTIVES: * Determine the frequency and duration of response in patients with recurrent small cell lung cancer treated with interferon alfa, isotretinoin, and paclitaxel. * Determine the toxic effects of this regimen in these patients. * Determine the duration of survival in patients treated with this regimen. * Correlate the levels of bcl-2 in peripheral blood monocytes with response and survival in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive interferon alfa subcutaneously and oral isotretinoin on days 1 and 2 and paclitaxel IV over 1 hour on day 2 of weeks 1-6. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 1 year. PROJECTED ACCRUAL: A total of 37-83 patients will be accrued for this study.
Interventions
BIOLOGICALinterferon alpha
Interferon alpha given subcutaneously, 6 million units per square meter of body surface area on days 1 and 2 of each week for 6 weeks, followed by 2 weeks of rest. Given until disease progression or unacceptable toxicity.
13-cis-retinoic acid given at 1 mg/kg of body weight by mouth on days 1 and 2 of each week for 6 weeks, followed by 2 weeks of rest. Given until disease progression or unacceptable toxicity.
DRUGpaclitaxel
paclitaxel administered intravenously with premedication at 75 mg/m2 of body surface area on day 2 of each week for 6 weeks, followed by 2 weeks of rest. Given until disease progression or unacceptable toxicity.
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
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
* Histologically or cytologically confirmed recurrent small cell lung cancer (SCLC) with clinically confirmed measurable disease * Age 18 and over * ECOG Performance status 0-3 * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Bilirubin no greater than 1.5 mg/dL * AST no greater than 2 times upper limit of normal (ULN) * Creatinine no greater than 1.5 mg/dL * Triglycerides no greater than 1.5 times ULN * Patients must have had prior chemotherapy treatment for SCLC, and toxicities must have resolved to less than or equal to grade 1 * Women of childbearing potential and sexually active males are strongly encouraged to use an accepted and effective method of contraception.
Exclusion criteria
* History of another neoplasm other than SCLC except for non-metastatic, non-melanoma skin cancers, carcinoma in situ of the cervix, or cancer cured by surgery or small field radiotherapy at least 5 years before registration * Pregnant or nursing, with a negative pregnancy test within 2 weeks prior to registration * Severe depression requiring medication * Use of the following drugs within 4 weeks prior to registration: carbamazepine, ethanol, tetracycline, doxycycline, minocycline, topical acne products containing Retin-A, vitamin A, cisplatin, ketoconazole, phenytoin or other antiepileptic drugs * Use of GM-CSF or G-CSF within 4 weeks prior to registration * Prior paclitaxel or interferon therapy * Radiation therapy within 60 days prior to registration * Chemotherapy within 60 days prior to registration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response by RECIST Criteria (v 1.0) | Assessed every 6 weeks | Number of eligible, treated participants in each response category by RECIST criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival | Assessed every 3 months for 1 year then every 6 months | Time from registration to death. |
| Progression-free Survival | Assessed every 6 weeks | Time from registration to documented disease progression (RECIST criteria) or death. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from ECOG member institutions between February 24, 2004 and August 22, 2007. The first patient was accrued on May 26, 2004.
Participants by arm
| Arm | Count |
|---|---|
| IFN 13CRA Paclitaxel Interferon alpha and 13-cis-retinoic acid given on days 1 and 2 and paclitaxel given on day 2 for six weeks of an eight-week cycle until disease progression or unacceptable toxicity | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible | 3 |
Baseline characteristics
| Characteristic | IFN 13CRA Paclitaxel |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Age, Continuous | 60 years |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 34 |
| serious Total, serious adverse events | 21 / 34 |
Outcome results
Primary
Response by RECIST Criteria (v 1.0)
Number of eligible, treated participants in each response category by RECIST criteria
Time frame: Assessed every 6 weeks
Population: Eligible, treated patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IFN 13CRA Paclitaxel | Response by RECIST Criteria (v 1.0) | Partial Response | 3 participants |
| IFN 13CRA Paclitaxel | Response by RECIST Criteria (v 1.0) | Stable Disease | 5 participants |
| IFN 13CRA Paclitaxel | Response by RECIST Criteria (v 1.0) | Progressive Disease | 11 participants |
| IFN 13CRA Paclitaxel | Response by RECIST Criteria (v 1.0) | Unevaluable | 15 participants |
Comparison: The study was designed to have adequate (90%) power to distinguish a true response rate of 50% from a null rate of 35% assuming total accrual of 76 patients in two stages. The design mandated that at least 13 objective responses be observed among 34 patients in the first stage in order to continue to the second stage. These were not observed, so the study stopped after the first stage. 90% exact binomial confidence intervals are provided for the response rate.90% CI: [2.4, 21.3]
Secondary
Progression-free Survival
Time from registration to documented disease progression (RECIST criteria) or death.
Time frame: Assessed every 6 weeks
Population: Eligible, treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IFN 13CRA Paclitaxel | Progression-free Survival | 2.0 months |
Secondary
Survival
Time from registration to death.
Time frame: Assessed every 3 months for 1 year then every 6 months
Population: Eligible, treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IFN 13CRA Paclitaxel | Survival | 6.2 months |