Clinical trial NCT00030771: Preoperative Chemoradiotherapy vs. Chemotherapy Alone in NSCLC Patients
Official title: Preoperative Chemoradiotherapy vs. Chemotherapy Alone in Non-small Cell Lung Cancer (NSCLC) Patients With Mediastinal Lymph Node Metastases (Stage IIIA, N2): A Randomized Prospective Phase III Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: squamous cell lung cancer
large cell lung cancer
stage IIIA non-small cell lung cancer
adenosquamous cell lung cancer
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2003-01-27
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as docetaxel and cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving chemotherapy with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known if chemotherapy plus radiation therapy is more effective than chemotherapy alone before surgery in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying docetaxel and cisplatin with or without radiation therapy to see how well they work when given before surgery in treating patients with stage IIIA non-small cell lung cancer that has spread to lymph nodes in the chest.

Detailed description: The main objective of this trial is to compare feasibility and efficacy of sequential neoadjuvant chemoradiotherapy with 44 Gy concomitant boost to neoadjuvant chemotherapy alone.

Secondary objectives are to assess the value of PET in predicting pathological response and eventfree survival in stage IIIA NSCLC, and a health economic analysis of the two regimens. Further to compare the amount of serum DNA in patients with stage IIIA, pN2 NSCLC before chemotherapy, before surgery and at the second follow-up visit (i.e. four months after surgery or treatment failure for patients who can not be operated) in patients randomized into the trial SAKK 16/00 and to correlate the DNA variation with tumor response, remission duration and overall survival.

OUTLINE: This is a prospective randomized phase III trial. Patients are stratified according to mediastinal bulk (5 cm or more vs less than 5 cm), weight loss in the past 6 months (5% or more vs less than 5%), and participating center. Patients are randomized to 1 of 2 treatment arms.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed non-small cell lung cancer

  * Squamous, adenosquamous, large cell, or poorly differentiated
* Stage IIIA (T1-3, N2, M0)

  * N2 disease confirmed by 1 of the following:

    * Mediastinoscopy
    * Bronchoscopy with fine-needle aspiration or esophagoscopy

      * All N3 lymph nodes must be negative by positron-emission tomography (PET) AND CT scan (\< 1 cm in the largest diameter)
    * PET scan

      * Both the primary tumor and at least 1 N2 lymph node must be positive in PET scan
      * At least 1 of the PET scan positive N2 lymph nodes is positive in the CT scan (\> 1 cm in the largest diameter)
      * All N3 lymph nodes negative in PET scan

PATIENT CHARACTERISTICS:

Age:

* 18 to 75

Performance status:

* WHO 0-1

Life expectancy:

* Not specified

Hematopoietic:

* WBC at least 4,000/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin normal
* AST/ALT no greater than 1.5 times upper limit of normal (ULN)
* Alkaline phosphatase no greater than 2.5 times ULN

Renal:

* Creatinine clearance greater than 60 mL/min

Cardiovascular:

* Cardiac function normal
* No unstable cardiac disease requiring treatment
* No congestive heart failure
* No angina pectoris even if medically controlled
* No significant arrhythmia
* No myocardial infarction in the past 3 months

Pulmonary:

* Lung function appropriate

Neurologic:

* No history of significant neurologic or psychiatric disorders
* No psychotic disorders
* No dementia
* No seizures

Other:

* No other prior or concurrent malignancies except nonmelanoma skin cancer, adequately treated carcinoma in situ of the cervix, or any other neoplastic disease with a disease-free interval ≥ 5 years
* No active uncontrolled infection
* No uncontrolled diabetes mellitus
* No gastric ulcers
* No pre-existing peripheral neuropathy greater than grade 1
* No contraindications to corticosteroids
* No other serious underlying medical condition that would preclude study participation
* No socioeconomic or geographic condition that would preclude study participation
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior cytostatic chemotherapy

Endocrine therapy:

* No concurrent prednisone except for treatment of acute hypersensitivity reactions or chronic low-dose treatment initiated more than 6 months prior to study entry (i.e., no greater than 20 mg methylprednisolone or equivalent)

Radiotherapy:

* No prior radiotherapy to chest

Surgery:

* Not specified

Other:

* At least 30 days since participation in another clinical study
* No other concurrent experimental drugs

Primary outcomes:
measure: Event-free survival
timeFrame: 1 month after surgery
Secondary outcomes:
measure: Postoperative mortality assessed
timeFrame: 1 month after surgery
measure: Toxicity (hematological, renal and neurological toxicities, nausea and vomiting, weight changes as well as esophageal toxicities)
timeFrame: During treatment
measure: Complete resection rate after surgery
timeFrame: 1 month after surgery
measure: Objective response rate measured after completion of chemoradiotherapy
timeFrame: 43 days
measure: Operability
timeFrame: 1 month after chemo
measure: Overall survival
timeFrame: Life-long follow-up until death of patient (up to 30 years)
measure: Failure pattern
timeFrame: Life-long follow-up until death of patient (up to 30 years)
Other outcomes:
Locations:
city: Löwenstein
country: Germany
facility: Klinik Loewenstein gGmbH
city: Mannheim
country: Germany
facility: Klinikum der Stadt Mannheim
city: Sremska Kamenica
country: Serbia
facility: Institut za plucne bolesti
city: Sremska Kamenica
country: Serbia
facility: Institute of Oncology
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Baden
country: Switzerland
facility: Kantonsspital
city: Basel
country: Switzerland
facility: Saint Claraspital AG
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Bruderholz
country: Switzerland
facility: Kantonsspital Bruderholz
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Freiburg
country: Switzerland
facility: Kantonsspital Freiburg
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Lausanne
country: Switzerland
facility: Centre Pluridisciplinaire d' Oncologie
city: Liestal
country: Switzerland
facility: Kantonsspital Liestal
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: Rheinfelden
country: Switzerland
facility: FMH Onkologie/Haematologie
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thun
country: Switzerland
facility: Regionalspital
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zurich
country: Switzerland
facility: Onkozentrum
city: Zurich
country: Switzerland
facility: City Hospital Triemli
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Kantonsspital Winterthur KSW
name: Miklos Pless, MD
role: STUDY_CHAIR
affiliation: Centre Hospitalier Universitaire Vaudois
name: Hans-Beat Ris, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitaetsspital-Basel
name: Diana Naehrig, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Universitaire Vaudoise
name: Roger Stupp, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tieu BH, Sanborn RE, Thomas CR Jr. Neoadjuvant therapy for resectable non-small cell lung cancer with mediastinal lymph node involvement. Thorac Surg Clin. 2008 Nov;18(4):403-15. doi: 10.1016/j.thorsurg.2008.07.004.
citation: Pless M, Stupp R, Ris HB, Stahel RA, Weder W, Thierstein S, Gerard MA, Xyrafas A, Fruh M, Cathomas R, Zippelius A, Roth A, Bijelovic M, Ochsenbein A, Meier UR, Mamot C, Rauch D, Gautschi O, Betticher DC, Mirimanoff RO, Peters S; SAKK Lung Cancer Project Group. Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. Lancet. 2015 Sep 12;386(9998):1049-56. doi: 10.1016/S0140-6736(15)60294-X. Epub 2015 Aug 11.