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Preoperative Chemoradiotherapy vs. Chemotherapy Alone in NSCLC Patients

Primary Purpose

Lung Cancer

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Chemotherapy
Radiotherapy
Surgery
Sponsored by
Swiss Group for Clinical Cancer Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring squamous cell lung cancer, large cell lung cancer, stage IIIA non-small cell lung cancer, adenosquamous cell lung cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

Neoadjuvant Chemoradiotherapy + Chemotherapy + Surgery

Neoadjuvant Chemotherapy + Surgery

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Postoperative mortality assessed
All deaths occurring within 30 days of the thoracic surgery to remove the primary tumor
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.
Complete resection rate after surgery
Assessed according to the NCIC-CTG Expanded Common Toxicity Criteria grading.
Objective response rate measured after completion of chemoradiotherapy
Response rate will be evaluated according to the WHO response criteria TNM classification after surgery.
Operability
Patients who are able to undergo radical resection of their lung cancer after neoadjuvant therapy, as assessed by the thoracic surgeon.
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.
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.

Full Information

First Posted
February 14, 2002
Last Updated
January 9, 2023
Sponsor
Swiss Group for Clinical Cancer Research
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1. Study Identification

Unique Protocol Identification Number
NCT00030771
Brief Title
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

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 4, 2001 (Actual)
Primary Completion Date
April 9, 2014 (Actual)
Study Completion Date
December 2037 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swiss Group for Clinical Cancer Research

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
squamous cell lung cancer, large cell lung cancer, stage IIIA non-small cell lung cancer, adenosquamous cell lung cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
232 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Active Comparator
Arm Description
Neoadjuvant Chemoradiotherapy + Chemotherapy + Surgery
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
Neoadjuvant Chemotherapy + Surgery
Intervention Type
Drug
Intervention Name(s)
Chemotherapy
Intervention Description
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
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
Radiotherapy (3 weeks after last chemotherapy administration) 44 Gy in 22 fractions concomitant boost technique in 3 weeks
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Description
3-4 weeks after termination of radiotherapy
Primary Outcome Measure Information:
Title
Event-free survival
Description
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.
Time Frame
1 month after surgery
Secondary Outcome Measure Information:
Title
Postoperative mortality assessed
Description
All deaths occurring within 30 days of the thoracic surgery to remove the primary tumor
Time Frame
1 month after surgery
Title
Toxicity (hematological, renal and neurological toxicities, nausea and vomiting, weight changes as well as esophageal toxicities)
Description
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.
Time Frame
During treatment
Title
Complete resection rate after surgery
Description
Assessed according to the NCIC-CTG Expanded Common Toxicity Criteria grading.
Time Frame
1 month after surgery
Title
Objective response rate measured after completion of chemoradiotherapy
Description
Response rate will be evaluated according to the WHO response criteria TNM classification after surgery.
Time Frame
43 days
Title
Operability
Description
Patients who are able to undergo radical resection of their lung cancer after neoadjuvant therapy, as assessed by the thoracic surgeon.
Time Frame
1 month after chemo
Title
Overall survival
Description
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.
Time Frame
Life-long follow-up until death of patient (up to 30 years)
Title
Failure pattern
Description
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.
Time Frame
Life-long follow-up until death of patient (up to 30 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Miklos Pless, MD
Organizational Affiliation
Kantonsspital Winterthur KSW
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Hans-Beat Ris, MD
Organizational Affiliation
Centre Hospitalier Universitaire Vaudois
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Diana Naehrig, MD
Organizational Affiliation
Universitaetsspital-Basel
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Roger Stupp, MD
Organizational Affiliation
Centre Hospitalier Universitaire Vaudoise
Official's Role
Principal Investigator
Facility Information:
Facility Name
Klinik Loewenstein gGmbH
City
Löwenstein
ZIP/Postal Code
74245
Country
Germany
Facility Name
Klinikum der Stadt Mannheim
City
Mannheim
ZIP/Postal Code
D-68135
Country
Germany
Facility Name
Institut za plucne bolesti
City
Sremska Kamenica
ZIP/Postal Code
21204
Country
Serbia
Facility Name
Institute of Oncology
City
Sremska Kamenica
ZIP/Postal Code
21204
Country
Serbia
Facility Name
Kantonsspital Aarau
City
Aarau
ZIP/Postal Code
CH-5001
Country
Switzerland
Facility Name
Kantonsspital Baden
City
Baden
ZIP/Postal Code
CH-5404
Country
Switzerland
Facility Name
Kantonsspital
City
Baden
ZIP/Postal Code
CH-5404
Country
Switzerland
Facility Name
Saint Claraspital AG
City
Basel
ZIP/Postal Code
CH-4016
Country
Switzerland
Facility Name
Universitaetsspital-Basel
City
Basel
ZIP/Postal Code
CH-4031
Country
Switzerland
Facility Name
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
City
Bellinzona
ZIP/Postal Code
6500
Country
Switzerland
Facility Name
Inselspital Bern
City
Bern
ZIP/Postal Code
CH-3010
Country
Switzerland
Facility Name
Kantonsspital Bruderholz
City
Bruderholz
ZIP/Postal Code
CH-4101
Country
Switzerland
Facility Name
Kantonsspital Graubuenden
City
Chur
ZIP/Postal Code
CH-7000
Country
Switzerland
Facility Name
Kantonsspital Freiburg
City
Freiburg
ZIP/Postal Code
1708
Country
Switzerland
Facility Name
Hopital Cantonal Universitaire de Geneve
City
Geneva
ZIP/Postal Code
CH-1211
Country
Switzerland
Facility Name
Centre Pluridisciplinaire d' Oncologie
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland
Facility Name
Kantonsspital Liestal
City
Liestal
ZIP/Postal Code
CH-4410
Country
Switzerland
Facility Name
Kantonsspital Olten
City
Olten
ZIP/Postal Code
CH-4600
Country
Switzerland
Facility Name
FMH Onkologie/Haematologie
City
Rheinfelden
ZIP/Postal Code
4310
Country
Switzerland
Facility Name
Kantonsspital - St. Gallen
City
St. Gallen
ZIP/Postal Code
CH-9007
Country
Switzerland
Facility Name
Regionalspital
City
Thun
ZIP/Postal Code
3600
Country
Switzerland
Facility Name
Kantonsspital Winterthur
City
Winterthur
ZIP/Postal Code
CH-8400
Country
Switzerland
Facility Name
Onkozentrum
City
Zurich
ZIP/Postal Code
8038
Country
Switzerland
Facility Name
City Hospital Triemli
City
Zurich
ZIP/Postal Code
CH-8063
Country
Switzerland
Facility Name
UniversitaetsSpital Zuerich
City
Zurich
ZIP/Postal Code
CH-8091
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
19086609
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.
Results Reference
background
PubMed Identifier
26275735
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. Erratum In: Lancet. 2015 Sep 12;386(9998):1040.
Results Reference
derived

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Preoperative Chemoradiotherapy vs. Chemotherapy Alone in NSCLC Patients

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