Carcinoma, Non-Small-Cell Lung, Lung Cancer
Conditions
Brief summary
The purpose of this study is to assess how well this particular combination of chemotherapy, radiation and surgery works to help people with locally advanced lung cancer, how well PET scans indicates whether someone has responded to chemotherapy and radiation, and gene expression patterns related to outcomes in patients with locally advanced lung cancer who receive this treatment regimen.
Interventions
DRUGDocetaxel
20 mg/m2, 75 mg/m2 infusion
DRUGCarboplatin
AUC of 2 and 6 infusion
PROCEDURERadiation therapy
NEOADJUVANT RADIOTHERAPY Radiation therapy will be concurrent with the chemotherapy. Radiation therapy will begin within 24 hours of chemotherapy. CONSOLIDATION RADIOTHERAPY Patients with positive surgical margins or incomplete resection (tumor shaved from spine or great vessels) will receive an additional boost of radiotherapy 3 to 6 weeks after surgery. This will be a 16 Gy boost given with concurrent weekly chemotherapy as during the neoadjuvant period.
PROCEDURESurgical resection
All patients will be taken to surgical excision, unless they have developed a condition other than progressive disease, which would make surgery unsafe.
Sponsors
Aventis Pharmaceuticals
Stanford University
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 confirmed stage IIIA or IIIB NSCLC * Patients must have measurable disease * No previous chemotherapy, radiation therapy or other systemic therapy for their NSCLC. * Age\>18 years * Life expectancy \>12 months * ECOG performance status 0-1 * Normal organ and marrow function * Medically fit for surgery at time of enrollment. * Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study. Women must have a negative pregnancy test prior to enrollment. * Ability to understand and willingness to sign the consent form.
Exclusion criteria
* Previous chemotherapy, radiation therapy or any other systemic treatment for their NSCLC. * Patients receiving any other investigational agents. * Known metastatic disease (brain or any other site) * History of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 or with allergic reactions to compounds of similar chemical composition to carboplatin or other agents used in the study. * Peripheral neuropathy \>grade 1 * Uncontrolled concurrent illness * Pregnant women * Weight loss\>10% in the past 3 months before diagnosis. * Hyperglycemia - exclusion from PET analysis * HIV positive patients receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with docetaxel and carboplatin or other agents administered during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2 Year Overall Survival After a Combination of Chemotherapy, Radiation and Surgery in Stage III NSCLC Patients Following the Protocol Therapy. | Two years | Patients were analyzed for 2 year overall survival after receiving trimodality (chemotherapy/radiation/surgery) therapy for stage III NSCLC. Patients had a chest x-ray and a doctor visit with a physical examination every 3 months after completion of all therapy for 3 years then every 6 months for 3 years to look for evidence of recurrent disease and to follow survival. Thoracic computed tomography (CT) scans were obtained at 6, 12, 18 months after completion of all therapy and then yearly for 3 years or as clinically indicated to evaluate for relapse. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Standard Uptake Value (SUVmax) on Positron Emission Tomography (PET) Scans Pre and Post Chemotherapy and Radiation in This Trial and Ability to Predict Surgical Resection Rate, Progression-free Survival and 2 Year Overall Survival | baseline, 5 weeks after combined chemo-radiation | The change in standardized uptake values (SUV)max on PET scans obtained pre- and after 5 weeks of combined chemo-radiation for patients enrolled on the trial were evaluated for ability to predict outcomes including complete resection at time of surgery (3-6 weeks after completion of the chemo-radiation), progression-free survival and 2 year overall survival. The mean SUVmax pre chemoradiation minus the mean SUVmax post-radiation is reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Analysis of Relation of Gene Expression Patterns to Outcomes in Patients With Locally Advanced Lung Cancer Who Receive This Treatment Regimen | Specimen collected at time of surgery | This analysis of gene expression patterns related to outcomes in patients with locally advanced lung cancer who received this treatment regimen was not performed due to lack of funding. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Group 1 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 24 |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 13 |
| serious Total, serious adverse events | 8 / 13 |
Outcome results
Primary
2 Year Overall Survival After a Combination of Chemotherapy, Radiation and Surgery in Stage III NSCLC Patients Following the Protocol Therapy.
Patients were analyzed for 2 year overall survival after receiving trimodality (chemotherapy/radiation/surgery) therapy for stage III NSCLC. Patients had a chest x-ray and a doctor visit with a physical examination every 3 months after completion of all therapy for 3 years then every 6 months for 3 years to look for evidence of recurrent disease and to follow survival. Thoracic computed tomography (CT) scans were obtained at 6, 12, 18 months after completion of all therapy and then yearly for 3 years or as clinically indicated to evaluate for relapse.
Time frame: Two years
Population: All patients alive and not censored at 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel / Carboplatin / XRT + Surgical Resection | 2 Year Overall Survival After a Combination of Chemotherapy, Radiation and Surgery in Stage III NSCLC Patients Following the Protocol Therapy. | 7 participants |
Comparison: 2-year overall survival (OS) Our null hypothesis was a probability of survival at 2 years of 0.30. The study was powered at 80% (with α 5% two-tailed) to detect a probability of survival at 2 years of 0.55. This would require 30 patients assuming accrual over 2 years with 1 year of additional follow-up. The probability of survival at 2 years of 0.55 is based on previous studies of neoadjuvant approaches with reported 2 year survival in the 40-60% range.95% CI: [0.36, 0.9]
Secondary
Change in Standard Uptake Value (SUVmax) on Positron Emission Tomography (PET) Scans Pre and Post Chemotherapy and Radiation in This Trial and Ability to Predict Surgical Resection Rate, Progression-free Survival and 2 Year Overall Survival
The change in standardized uptake values (SUV)max on PET scans obtained pre- and after 5 weeks of combined chemo-radiation for patients enrolled on the trial were evaluated for ability to predict outcomes including complete resection at time of surgery (3-6 weeks after completion of the chemo-radiation), progression-free survival and 2 year overall survival. The mean SUVmax pre chemoradiation minus the mean SUVmax post-radiation is reported.
Time frame: baseline, 5 weeks after combined chemo-radiation
Population: All enrolled patients were analyzed in the published manuscript
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Docetaxel / Carboplatin / XRT + Surgical Resection | Change in Standard Uptake Value (SUVmax) on Positron Emission Tomography (PET) Scans Pre and Post Chemotherapy and Radiation in This Trial and Ability to Predict Surgical Resection Rate, Progression-free Survival and 2 Year Overall Survival | 5.7 standardized uptake value (SUV)max | Standard Deviation 5.3 |
Other Pre-specified
Exploratory Analysis of Relation of Gene Expression Patterns to Outcomes in Patients With Locally Advanced Lung Cancer Who Receive This Treatment Regimen
This analysis of gene expression patterns related to outcomes in patients with locally advanced lung cancer who received this treatment regimen was not performed due to lack of funding.
Time frame: Specimen collected at time of surgery
Population: Plan was to analyze all patients with adequate tissue for this analysis, but was not done. We did not have sufficient funds for this analysis.