Preoperative Chemoradiotherapy vs. Chemotherapy Alone in NSCLC Patients

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00030771
• Other study ID #: SAKK 16/00
• Secondary ID: SWS-SAKK-16/00EU
• Status: Completed
• Phase: Phase 3
• Start date: April 4, 2001
• Est. completion date: September 15, 2023

Study information

• Verified date: January 2024
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 232
• Est. completion date: September 15, 2023
• Est. primary completion date: April 9, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• Chemotherapy
Docetaxel (Taxotere®) 85 mg/m2 1 hour iv infusion d1 Cisplatin 100 mg/m2 1 hour iv infusion d1 Schedule: 3 cycles repeated every 21 days

Radiation:
• Radiotherapy
Radiotherapy (3 weeks after last chemotherapy administration) 44 Gy in 22 fractions concomitant boost technique in 3 weeks

Procedure:
• Surgery
3-4 weeks after termination of radiotherapy

Locations

Country	Name	City	State
Germany	Klinik Loewenstein gGmbH	Löwenstein
Germany	Klinikum der Stadt Mannheim	Mannheim
Serbia	Institut za plucne bolesti	Sremska Kamenica
Serbia	Institute of Oncology	Sremska Kamenica
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Kantonsspital	Baden
Switzerland	Kantonsspital Baden	Baden
Switzerland	Saint Claraspital AG	Basel
Switzerland	Universitaetsspital-Basel	Basel
Switzerland	Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli	Bellinzona
Switzerland	Inselspital Bern	Bern
Switzerland	Kantonsspital Bruderholz	Bruderholz
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	Kantonsspital Freiburg	Freiburg
Switzerland	Hopital Cantonal Universitaire de Geneve	Geneva
Switzerland	Centre Pluridisciplinaire d' Oncologie	Lausanne
Switzerland	Kantonsspital Liestal	Liestal
Switzerland	Kantonsspital Olten	Olten
Switzerland	FMH Onkologie/Haematologie	Rheinfelden
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	Regionalspital	Thun
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	City Hospital Triemli	Zurich
Switzerland	Onkozentrum	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Countries where clinical trial is conducted

Germany,  Serbia,  Switzerland, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival	Time from randomization to relapse/progression/second tumor/death, whichever occurs first (for all randomized patients). If no event is observed, the patients will be censored at the last time they were known to be alive.	1 month after surgery
Secondary	Postoperative mortality assessed	All deaths occurring within 30 days of the thoracic surgery to remove the primary tumor	1 month after surgery
Secondary	Toxicity (hematological, renal and neurological toxicities, nausea and vomiting, weight changes as well as esophageal toxicities)	Assessed according to the NCIC-CTG Expanded Common Toxicity Criteria grading. Special attention shall be given to hematological, renal and neurological toxicities, nausea and vomiting, weight changes as well as esophageal toxicities.	During treatment
Secondary	Complete resection rate after surgery	Assessed according to the NCIC-CTG Expanded Common Toxicity Criteria grading.	1 month after surgery
Secondary	Objective response rate measured after completion of chemoradiotherapy	Response rate will be evaluated according to the; WHO response criteria; TNM classification after surgery.	43 days
Secondary	Operability	Patients who are able to undergo radical resection of their lung cancer after neoadjuvant therapy, as assessed by the thoracic surgeon.	1 month after chemo
Secondary	Overall survival	Calculated from randomization to the date of death from any cause. Patients not experiencing an event will be censored at the last time they were known to be alive.	Life-long follow-up until death of patient (up to 30 years)
Secondary	Failure pattern	Defined as location of first tumor progression or relapse. Failure can be local relapse (area of primary tumor or mediastinum), distant relapse (all others) or the combination thereof.	Life-long follow-up until death of patient (up to 30 years)