Preoperative Chemoradiotherapy vs. Chemotherapy Alone in NSCLC Patients

Swiss Group for Clinical Cancer Research

Status and phase: Completed; Phase 3

Conditions: Lung Cancer

Treatments: Procedure: Surgery; Drug: Chemotherapy; Radiation: Radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00030771

SAKK 16/00

SWS-SAKK-16/00 (Other Identifier)

EU-20138

Details and patient eligibility

About

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.

Full 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.

Enrollment: 232 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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232 participants in 2 patient groups

Arm A

Active Comparator group

Description:

Neoadjuvant Chemoradiotherapy + Chemotherapy + Surgery

Treatment:

Drug: Chemotherapy

Radiation: Radiotherapy

Procedure: Surgery

Arm B

Active Comparator group

Description:

Neoadjuvant Chemotherapy + Surgery

Treatment:

Drug: Chemotherapy

Procedure: Surgery