Preoperative Chemoradiotherapy vs. Chemotherapy Alone in NSCLC Patients

NCT ID: NCT00030771

Last Updated: 2024-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 232 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-04-04
• Study Completion Date: 2023-09-15

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.

Conditions

Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Neoadjuvant Chemoradiotherapy + Chemotherapy + Surgery

Group Type: ACTIVE_COMPARATOR

Chemotherapy

Intervention Type: DRUG

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

Radiotherapy

Intervention Type: RADIATION

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

Surgery

Intervention Type: PROCEDURE

3-4 weeks after termination of radiotherapy

Arm B

Neoadjuvant Chemotherapy + Surgery

Group Type: ACTIVE_COMPARATOR

Chemotherapy

Intervention Type: DRUG

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

Surgery

Intervention Type: PROCEDURE

3-4 weeks after termination of radiotherapy

Interventions

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

Intervention Type: DRUG

Radiotherapy

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

Intervention Type: RADIATION

Surgery

3-4 weeks after termination of radiotherapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Miklos Pless, MD

Role: STUDY_CHAIR

Kantonsspital Winterthur KSW

Hans-Beat Ris, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Vaudois

Diana Naehrig, MD

Role: PRINCIPAL_INVESTIGATOR

Universitaetsspital-Basel

Roger Stupp, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Vaudoise

Locations

Klinik Loewenstein gGmbH

Löwenstein, , Germany

Klinikum der Stadt Mannheim

Mannheim, , Germany

Institut za plucne bolesti

Kamenitz, , Serbia

Institute of Oncology

Kamenitz, , Serbia

Kantonsspital Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Kantonsspital

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

Fribourg, , 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

Sankt Gallen, , Switzerland

Regionalspital

Thun, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Onkozentrum

Zurich, , Switzerland

City Hospital Triemli

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Germany; Serbia; Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 19086609 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26275735 (View on PubMed)

Other Identifiers

SWS-SAKK-16/00

Identifier Type: OTHER

Identifier Source: secondary_id

EU-20138

Identifier Type: -

Identifier Source: secondary_id

SAKK 16/00

Identifier Type: -

Identifier Source: org_study_id