Know Cancer

forgot password

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)

Phase 2
18 Years
Open (Enrolling)
Non Small Cell Lung Cancer

Thank you

Trial Information

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
study initiation.

- 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.

Inclusion Criteria:

- Provision of a signed and dated written informed consent document prior to any study
specific procedures.

- Age ≥18 years, male or female.

- Histologically confirmed NSCLC.

- Specimen tumor tissue obtained from mediastinoscopy

- ECOG Performance status (PS) 0-1.

- Stage IIIA(N2) patients with technical operable disease limited to T1a,b, T2a,b N2
M0; T3 (>7 cm) N2 M0.

- Medically fit for resection by lobectomy or pneumonectomy.

- Radiologically measurable disease (RECIST v1.1 criteria).

- Prior surgery for NSCLC if resected ≥5 years.

- No prior chemotherapy, targeted-therapy, investigational therapy or radiation for

- No uncontrolled medical problems.

- No superior vena cava syndrome.

- Peripheral neuropathy must be ≤ grade 1.

- Acceptable hematologic and chemistry parameters.

- Creatinine clearance >50 ml/min.

- Female patients or their partners must be surgically sterile or be postmenopausal, or
agree to use effective contraception while in trial treatment and for 3 months

- Female patients with reproductive potential must have a negative pregnancy test
(serum or urine) within 72 hours prior to starting treatment.

- Patients who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures including patient reported measures.

Exclusion Criteria:

- Any evidence of mixed histology including elements of small cell or carcinoid lung

- Stage IIIA patients limited to T3 N1 M0; T3 (invasion) N2 M0; T4 N0, N1 M0.

- Any clinically significant GI abnormalities, which may impair intake, transit or
absorption of gefitinib, such as the inability to take oral medication.

- Current enrollment in another therapeutic clinical trial.

- Any psychiatric or cognitive disorder that would limit the understanding or rendering
of informed consent and/or compromise compliance with the requirements of this study.

- Past medical history of interstitial lung disease, drug-induced interstitial disease,
radiation pneumonitis which required steroid treatment or any evidence of clinically
active interstitial lung disease

- Pre-existing idiopathic pulmonary fibrosis evidence by computerized tomography (CT)
scan at baseline.

- Uncontrolled or significant CV disease, including: myocardial infarction within 12
months; uncontrolled angina within 6 months; congestive heart failure within 6
months; diagnosed or suspected congenital long QT syndrome;

- Any history of clinically significant ventricular arrhythmias (such as ventricular
tachycardia, ventricular fibrillation, or Torsades de pointes);

- Prolonged QTc interval on pre entry ECG.

- Any history of second or third degree heart block (may be eligible if currently have
a pacemaker);

- Heart rate <50/minute on baseline ECG;

- Uncontrolled hypertension.

- Evidence of prior malignancy (other than non melanoma skin cancer or in situ cervical
cancer, or localized and presumed cured prostate cancer with PSA < ULN) within the
last 3 years.

- Other severe acute or chronic medical condition that may increase the risk associated
with trial participation or may interfere with the interpretation of trial results
and, in the judgment of the investigator.

- Patients in whom corticosteroid premedication was contraindicated.

- HIV-positive patients on active treatment.

- Medications are prohibited at baseline and prior to randomization if they affect the
pharmacokinetics of gefitinib, cisplatin, docetaxel, gemcitabine, vinorelbine and
pemetrexed or if they are mainly metabolized by CYP3A4.

- Patients who are otherwise eligible can be enrolled only if drug substitution is
performed with acceptable clinical outcome prior to enrollment: known severe
hypersensitivity to gefitinib or other chemotherapeutic agents or any of the
excipients of the products.

- Pregnancy or breast-feeding.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pathologic Complete Response

Outcome Time Frame:

30 days

Safety Issue:


Principal Investigator

Francesco Grossi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy


Italy: Ethics Committee

Study ID:

CONTEST TRIAL RF-2009-1530324



Start Date:

July 2012

Completion Date:

December 2014

Related Keywords:

  • Non Small Cell Lung Cancer
  • NSCL
  • biomarkers
  • Customized Neoadjuvant Therapy
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms