Non-Small Cell Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer
Brief summary
In a previous phase II study, patients with pathological stage IIIb (without pleural effusion) NSCLC were treated with concurrent cisplatin and etoposide plus thoracic radiotherapy followed by 3 cycles of consolidation therapy with docetaxel. Docetaxel was selected based upon a survival benefit in patients with recurrent NSCLC. This trial will evaluate the role of consolidation therapy with docetaxel in patients with unresectable stage III disease. The purpose of the trial is to evaluate survival and toxicities of the regimens employed.
Detailed description
OUTLINE: This is a multi-center study. * Cisplatin 50 mg/m2 d1, 8, 29, 36 * Etoposide 50 mg/m2/day d1-5, 29-33 * Radiation 5940 cGy (180 cGy/day) Patients with CR, PR, SD Randomized to either:Docetaxel75 mg/m2 q3wk X 3 cycles or Observation Only Performance Status: ECOG 0 or 1 Life Expectancy: Not specified Hematopoietic: * ANC \> 1,500/mm3 * Platelet count \> 100,000/mm3 * Hemoglobin \> 8 g/dl. PRBC transfusions will be allowed to increase hemoglobin to \>8 g/dl Hepatic: * Serum bilirubin \< institutional upper limit of normal (ULN) * AST \< 2.5 X the upper limits of normal if alkaline phosphatase is \< ULN, or alkaline phosphatase may be up to 4 X ULN if AST are \< ULN Renal: * Serum creatinine of \< 2 mg/dl or calculated creatinine clearance \> 50 cc/min Cardiovascular: * No clinically significant history of cardiac disease, (i.e. uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the past year, or cardiac ventricular arrhythmias requiring medication). Pulmonary: * Pre-registration FEV1 \> 1 liters by spirometry within 42 days prior to study treatment.
Interventions
DRUGCisplatin
Cisplatin 50 mg/m2 day 1, 8, 29, 36
DRUGEtoposide
Etoposide 50 mg/m2, days 1-5, 29-33
RADIATIONRadiation
Radiation 5940 cGy (180 cGy/day)
DRUGDocetaxel
docetaxel 75mg/m2 q3wk x 3 cycles
Sponsors
Sanofi
Walther Cancer Institute
Nasser Hanna, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic or cytologic evidence of NSCLCUnresectable Stage IIIA (N2) OR Stage IIIB NSCLC. * Unresectable Stage IIIA will be defined by the following criteria: * N2 mediastinal lymph nodes must be multiple and/or bulky on CT scan such that in the opinion of the treating investigator, the patient is not a candidate for surgical resection * N2 disease must be documented by biopsy, FDG-PET scan imaging, or by CT if nodes are \> 2 cm on CT scan * Stage IIIb patients must have N3 or T4 status. N3 status must be documented by one of the following criteria: * Contralateral (to the primary tumor) mediastinal lymph node, supraclavicular or scalene lymph nodes proven by biopsy, FDG-PET scan imaging, or by CT if nodes are \> 2 cm on CT scan. * Patients with positive supraclavicular or scalene lymph nodes must not have disease extending up into the cervical region. * All patients must have measurable or evaluable disease documented by CT, MRI, X-ray or physical exam within 28 days prior to study treatment. * Negative pregnancy test Eligibility for Consolidation Therapy * Following completion of induction chemoradiotherapy patients without local progression of disease or distant metastases will then be randomized to receive consolidation therapy with docetaxel or observation. Patients will be stratified and randomized based on stage IIIa vs IIIb disease at baseline, CR vs. non-CR following induction chemoradiation, and ECOG PS 0 or 1 vs. 2. * Patients must have completed chemoradiotherapy per protocol and at least 4 weeks but no more than 8 weeks must have elapsed from the last day of induction therapy (the last day of radiation) to be eligible for randomization to consolidation with docetaxel or observation. * Patients must have undergone re-staging tests according to the study calendar and determined to have no evidence of disease progression to be eligible for randomization to consolidation with docetaxel or observation. * Patients must have an ANC \> 1,500/mm3, platelet count \> 100,000/ mm3, and hemoglobin \> 8 g/dl obtained within 14 days prior to registration for randomization to consolidation with docetaxel or observation. * Patients must have adequate hepatic function as defined by a serum bilirubin \< institutional upper limit of normal (ULN) and an AST and/or ALT \< 2.5 X the upper limits of normal if alkaline phosphatase is \< ULN, or alkaline phosphatase may be up to 4 X ULN if transaminases are \< ULN within 14 days prior to registration for randomization to consolidation with docetaxel or observation.
Exclusion criteria
* No prior chemotherapy or radiotherapy for lung cancer. * No unintended weight loss \> 5% body weight in the preceding 3 months prior to study treatment will not be eligible for this trial. * No symptomatic peripheral neuropathy prior to entry onto the study. Peripheral neuropathy must be \< Grade 1 to be eligible. * No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years. * No history of allergic reactions to drugs utilizing the vehicle polysorbate 80 (docetaxel) and polysorbate 80 + polyethylene glycol (etoposide). * If the patient has hearing loss at pre-study, performance of an audiogram is recommended (not mandatory) to document baseline hearing status in the event of possible further hearing loss due to cisplatin administration. * No current breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Participants were measured from treatment initiation to death | A comparison of overall survival following cisplatin/etoposide/radiotherapy between the consolidation docetaxel and observation arms was analyzed using Kaplan-Meier analysis. Median survival time and a log rank test were used to analyze the hypothesized improvement in overall survival. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Participants were monitored from treatment initiation until disease progression per RECIST or death | A comparison of progression free survival following cisplatin/etoposide/radiotherapy between the consolidation docetaxel and observation arms was analyzed using Kaplan-Meier analysis. Median PFS time and a log rank test were used to analyze the hypothesized improvement in progression free survival. Progression is defined by RECIST as a 20% increase in the sum of longest diameters of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) or by the appearance of a new lesion. |
Countries
United States
Participant flow
Pre-assignment details
77 patients who started the pre-randomization arm were not randomized due to the following reasons: toxicities, disease progression, ineligibility, patient decision, death, physician decision, and other miscellaneous reasons. Only patients who were randomized to consolidation therapy or observation are included in the study analysis.
Participants by arm
| Arm | Count |
|---|---|
| Pre-Randomization Prior to randomization patients received Cisplatin 50 mg/m\^2 days 1,8,29,36 + Etoposide 50 mg/m\^2 days 1-5, 29-33 + Radiation 5940 cGy (180 cGy/day). Patients with CR, PR or SD with manageable toxicity were randomized to either Docetaxel arm or Observation only arm.
Cisplatin: Cisplatin 50 mg/m2 day 1, 8, 29, 36
Etoposide: Etoposide 50 mg/m2, days 1-5, 29-33
Radiation: Radiation 5940 cGy (180 cGy/day) | 243 |
| Total | 243 |
Baseline characteristics
| Characteristic | Pre-Randomization |
|---|---|
| Age, Continuous | 63.0 years STANDARD_DEVIATION 9.5 |
| Percentage of participants with Stage IIIa vs IIIb disease at baseline | 41.15 percentage |
| Region of Enrollment United States | 243 participants |
| Sex: Female, Male Female | 82 Participants |
| Sex: Female, Male Male | 161 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 63 / 77 | 73 / 84 | 79 / 82 |
| serious Total, serious adverse events | 44 / 77 | 43 / 84 | 29 / 82 |
Outcome results
Primary
Overall Survival
A comparison of overall survival following cisplatin/etoposide/radiotherapy between the consolidation docetaxel and observation arms was analyzed using Kaplan-Meier analysis. Median survival time and a log rank test were used to analyze the hypothesized improvement in overall survival.
Time frame: Participants were measured from treatment initiation to death
Population: The analysis cohort for the results reported below are based on a planned interim DSMB evaluation conducted in 2006. This evaluation concluded that further accrual was futile and the study should be terminated. The 203 subjects included in this analysis had data sufficiently mature at the time of the DSMB analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Consolidation Docetaxel | Overall Survival | 21.5 Months |
| Observation Only | Overall Survival | 24.1 Months |
p-value: 0.883Log Rank
Secondary
Progression Free Survival
A comparison of progression free survival following cisplatin/etoposide/radiotherapy between the consolidation docetaxel and observation arms was analyzed using Kaplan-Meier analysis. Median PFS time and a log rank test were used to analyze the hypothesized improvement in progression free survival. Progression is defined by RECIST as a 20% increase in the sum of longest diameters of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) or by the appearance of a new lesion.
Time frame: Participants were monitored from treatment initiation until disease progression per RECIST or death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Consolidation Docetaxel | Progression Free Survival | 12.3 months |
| Observation Only | Progression Free Survival | 12.9 months |