A Multi-center Phase II Randomized Study of Customized Neoadjuvant Therapy Versus Standard Chemotherapy in Non-small Cell Lung Cancer (NSLC) Patients With Resectable Stage IIIA (N2) Disease (CONTEST-TRIAL)
- Subjects will be stratified by histology and biological markers (ERCC1, RRM1, TS, EGFR
mutation). Randomization will be centralized at the coordinating centre site. Patients will
receive chemotherapy with cisplatin + docetaxel or customized therapy for 3 cycles (60 days
with gefitinib) before surgery.
Every 4 months for 3 years and then every 6 months for 2 years following surgery, subjects
will be assessed by the investigator for adverse events related to study drug, documentation
of post study therapies received, DFS, and survival.
- Periodic evaluations of the trial data will be conducted by an independent data monitoring
committee to ensure subject safety and the validity and scientific merit of the study.
Assuming that the study is not stopped at the planned futility analyses or for safety
reasons, the final analysis will take place after the targeted number of events
(pathological complete response) is reached, which is estimated to take place 24 months post
- The pathological complete response (pCR)in the two groups will be computed in the ITT
populations and compared by means of the chi-square test without continuity correction. For
exploratory purposes, a multivariate logistic regression model will be fitted to the data,
with the pCR as the response variable and treatment (standard/ experimental) and
histo/molecular subgroup as covariate. The heterogeneity of the relative efficacy of the
tailored approach in the various subgroups (=subgroup analysis) will be evaluated by
including in the model the appropriate set of treatment-by-subgroup interaction terms, using
the standard likelihood ratio test. Time-to-event analyses (DFS and OS) will use standard
Kaplan-Meier estimators (with the Log-rank test) and semi-parametric PH regression models.
Safety will be summarized based on adverse events, vital signs and laboratory assessments. A
group sequential design is used to compare the Overall Survival in the two study arms.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Pathologic Complete Response
Francesco Grossi, MD
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Italy: Ethics Committee
CONTEST TRIAL RF-2009-1530324