Lung Cancer
Conditions
Keywords
stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer, large cell lung cancer, squamous cell lung cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Erlotinib may make tumor cells more sensitive to radiation therapy. Giving carboplatin and paclitaxel albumin-stabilized nanoparticle formulation together with radiation therapy and erlotinib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving carboplatin and paclitaxel albumin-stabilized nanoparticle formulation together with radiation therapy and erlotinib works in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery.
Detailed description
OBJECTIVES: Primary * To determine the activity of induction chemotherapy comprising carboplatin and paclitaxel albumin-stabilized nanoparticle formulation followed by concurrent thoracic radiotherapy and erlotinib hydrochloride in patients with poor-risk, unresectable stage IIIA or IIIB non-small cell lung cancer. Secondary * To determine the response rate and progression-free survival of these patients. OUTLINE: Patients receive induction chemotherapy comprising paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patient with rapid disease progression outside of the chest after induction therapy are removed from study. Patients with intrathoracic disease progression within the potential radiation field may continue protocol therapy at the discretion of the Study Chair. Patients with no disease progression outside the planned radiation field (either regional or distant) proceed to concurrent erlotinib hydrochloride and radiotherapy. Beginning on day 43 (week 7), patients receive oral erlotinib hydrochloride once daily. Patients also undergo concurrent radiotherapy 5 days a week for up to 7 weeks (33 fractions) in the absence of rapid disease progression outside of the chest or unacceptable toxicity. After completion of study therapy, patients are followed every 3 months for 1 year, and then every 6 months for up to 2 years
Interventions
DRUGcarboplatin
DRUGerlotinib hydrochloride
DRUGpaclitaxel albumin-stabilized nanoparticle formulation
RADIATIONradiation therapy
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
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 or cytologically confirmed non-small cell lung cancer (NSCLC), including any of the following histologies: * Squamous cell carcinoma * Adenocarcinoma (including bronchoalveolar cell) * Large cell anaplastic carcinoma (including giant and clear cell carcinomas) * Must meet the following criteria: * T1-3 with N2 and selected N3\* * T4 with N0, N1, N2 and selected N3\* * M0 (no M1 patients) NOTE: \*Patients with contralateral mediastinal disease (i.e., N3) are eligible, provided all gross disease can be encompassed within the radiation boost field in accordance with the homogeneity criteria. Patients with ipsilateral scalene or supraclavicular disease are also eligible. Patients with contralateral hilar or supraclavicular node involvement are not eligible. * Must have measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan * Nonmeasurable lesions include the following: * Bone lesions * Leptomeningeal disease * Ascites * Pleural or pericardial effusion * Abdominal masses that are not confirmed and followed by imaging techniques * Cystic lesions * Tumor lesions situated in a previously irradiated area * Patients must be considered unresectable or inoperable AND be deemed candidates for combined modality therapy by a medical oncologist and a radiation oncologist * Considered to be poor-risk with NCI CTC performance status (PS) 2 OR PS 0-1 and ≥ 10% weight loss within the past 3 months * Patients with tumors adjacent to a vertebral body are eligible, provided all gross disease can be encompassed within the radiation boost field in accordance with the homogeneity criteria * Pleural effusions meeting the following criteria allowed: * Effusion is transudate, cytologically negative, and non-bloody * Effusion can be seen on the chest CT scan but not on the chest x-ray AND is too small to tap * Effusion appears only after a thoracotomy or other invasive thoracic procedure was attempted PATIENT CHARACTERISTICS: * See Disease Characteristics * Granulocytes ≥ 1,500/μL * Platelet count ≥ 100,000/μL * Creatinine ≤ 1.5 x upper limit of normal (ULN) * AST \< 2 x ULN * Bilirubin ≤ ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * No prior chemotherapy or radiotherapy for NSCLC * At least 2 weeks since formal exploratory thoracotomy * No concurrent administration of sucralfate suspension and erlotinib hydrochloride * No concurrent intensity-modulated radiotherapy * No concurrent hormones or other chemotherapeutic agents except steroids given for adrenal failure, hormones administered for non-disease-related conditions (e.g., insulin for diabetes), and intermittent use of dexamethasone as an antiemetic * No concurrent palliative radiotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival at 12 Months | At 12 months | Percentage of participants who were alive at 12 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | Duration of study (up to 2 years) | Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: * Complete Response (CR): disappearance of all target lesions; * Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; * Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; * Stable Disease (SD): small changes that do not meet above criteria. Response rate is reported as the percentage of participants who achieved each response. |
| Progression-free Survival | Duration of study (up to 2 years) | Progression free survival (PFS) is defined as the time from registration to disease progression or death of any cause, which ever comes first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. |
Countries
United States
Participant flow
Recruitment details
Between March 2008 and October 2011, 78 participants were recruited to this study.
Pre-assignment details
Three participants did not receive any protocol treatment and were excluded from all analyses.
Participants by arm
| Arm | Count |
|---|---|
| Paclitaxel + Carboplatin + Radiation + Erlotinib Patients receive paclitaxel 100 mg/m\^2 IV over 30 minutes on days 1 and 8 and carboplatin AUC=5 IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses.
Beginning on day 43 (week 7), patients receive oral erlotinib hydrochloride 150 mg once daily. Patients also undergo concurrent radiotherapy 200 cGy/day, 5 days a week for up to 7 weeks (33 fractions), total dose of 6600 cGy. | 75 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Progression | 4 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Paclitaxel + Carboplatin + Radiation + Erlotinib |
|---|---|
| Age, Continuous | 68 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 69 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 20 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 | 0 Participants |
| Race (NIH/OMB) White | 53 Participants |
| Region of Enrollment United States | 75 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 71 / 75 |
| serious Total, serious adverse events | 19 / 75 |
Outcome results
Primary
Overall Survival at 12 Months
Percentage of participants who were alive at 12 months.
Time frame: At 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel + Carboplatin + Radiation + Erlotinib | Overall Survival at 12 Months | 57 percentage of participants |
Secondary
Progression-free Survival
Progression free survival (PFS) is defined as the time from registration to disease progression or death of any cause, which ever comes first. The median PFS with 95% CI was estimated using the Kaplan-Meier method.
Time frame: Duration of study (up to 2 years)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paclitaxel + Carboplatin + Radiation + Erlotinib | Progression-free Survival | 11 months |
Secondary
Response Rate
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: * Complete Response (CR): disappearance of all target lesions; * Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; * Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; * Stable Disease (SD): small changes that do not meet above criteria. Response rate is reported as the percentage of participants who achieved each response.
Time frame: Duration of study (up to 2 years)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paclitaxel + Carboplatin + Radiation + Erlotinib | Response Rate | Complete Response (CR) | 8 percentage of participants |
| Paclitaxel + Carboplatin + Radiation + Erlotinib | Response Rate | Partial Response (PR) | 59 percentage of participants |
| Paclitaxel + Carboplatin + Radiation + Erlotinib | Response Rate | Stable Disease (SD) | 27 percentage of participants |
| Paclitaxel + Carboplatin + Radiation + Erlotinib | Response Rate | Progressive Disease (PD) | 7 percentage of participants |