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Phase III Randomized Trial of Preoperative Chemotherapy Versus Preoperative Concurrent Chemotherapy and Thoracic Radiotherapy Followed by Surgical Resection and Consolidation Chemotherapy in Favorable Prognosis Patients With Stage IIIA (N2) Non-Small Cell Lung Cancer

Phase 3
18 Years
Not Enrolling
Lung Cancer

Thank you

Trial Information

Phase III Randomized Trial of Preoperative Chemotherapy Versus Preoperative Concurrent Chemotherapy and Thoracic Radiotherapy Followed by Surgical Resection and Consolidation Chemotherapy in Favorable Prognosis Patients With Stage IIIA (N2) Non-Small Cell Lung Cancer



- Compare overall survival of patients with newly diagnosed favorable prognosis stage
IIIA non-small cell lung cancer treated with neoadjuvant cisplatin and docetaxel with
vs without thoracic conformal radiotherapy followed by surgical resection and


- Compare median and progression-free survival of patients treated with these regimens.

- Compare clinical and pathologic response rates in patients treated with these regimens.

- Compare the toxicity of these regimens in these patients.

- Correlate pathological complete response with disease-free and overall survival of
patients treated with these regimens.

- Correlate DNA damage repair genes (ERCC1 and XRCC1), microtubule-related proteins
(TUBB-III and MAP4), and shed tumor DNA with response and outcome in patients treated
with these regimens.

- Correlate protein profiles, using MALDI-TOF proteomic analysis of tumor and serum, with
response and prognosis in patients treated with these regimens.

- Compare quality of life of patients treated with these regimens.

- Determine the efficacy of fludeoxyglucose F 18 positron emission tomography scanning in
assessing pathological response of the tumor and the mediastinal lymph nodes and in
predicting long-term outcome in patients treated with these regimens.

- Correlate comorbid conditions with survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to T
stage (T1 vs T2-3), number of involved mediastinal lymph nodes (1 vs 2 or more vs not
evaluable), and nodal micrometastases vs clinically involved nodes (mN2 vs cN2).

- Induction therapy: Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive cisplatin IV over 1 hour and docetaxel IV over 1 hour on
days 1 and 22.

- Arm II: Patients undergo thoracic conformal radiotherapy once daily 5 days a week
for approximately 5½ weeks (total of 28 doses). Patients also receive cisplatin IV
over 1 hour on days 1, 8, 22, and 29 and docetaxel IV over 1 hour on days 1, 8,
15, 22, and 29.

- Surgery: Within 4-8 weeks after completion of induction therapy, patients with stable
disease or better undergo a lobectomy or pneumonectomy with a formal systematic
mediastinal lymph node dissection.

- Consolidation therapy: Beginning 4-6 weeks after surgery, patients receive docetaxel IV
over 1 hour on days 1, 22, and 43 and pegfilgrastim or filgrastim (G-CSF)
subcutaneously on days 2, 23, and 44.

Quality of life is assessed at baseline, within 2 weeks after completion of induction
therapy, and then at 6 and 12 months after surgery.

After completion of study treatment, patients are followed every 3 months for 1 year, every
6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 574 patients will be accrued for this study within 4 years.

Inclusion Criteria


- Histologically or cytologically confirmed primary non-small cell lung cancer
(NSCLC)*, including any of the following cellular types:

- Adenocarcinoma

- Squamous cell carcinoma

- Large cell carcinoma

- Non-lobar and non-diffuse bronchoalveolar cell carcinoma

- NSCLC not otherwise specified NOTE: *Diagnosed within the past 3 months;
diagnosis by mediastinal nodal biopsy or needle aspiration allowed provided a
distinct lung primary (separate from the nodes) is clearly evident on CT scan

- Stage IIIA disease

- T1-T3 disease

- If pleural effusion is present, must meet ≥ 1 of the following criteria to
exclude T4 disease:

- Pleural effusion cytologically negative by thoracentesis

- Documented absence of pleural metastases and pleural effusion
cytologically negative by thoracoscopy (for patients with pleural
effusion on CT scan [but not on chest x-ray] that is deemed too small
to tap safely under either CT scan or ultrasound guidance)

- Confirmed positive ipsilateral mediastinal lymph node(s) (N2 disease)**, with or
without positive ipsilateral hilar nodes, by mediastinoscopy, mediastinotomy,
endoscopic ultrasound-guided transesophageal biopsy, thoracotomy, video-assisted
thoracoscopy, Wang needles, or fine needle aspiration under bronchoscopic or CT

- N2 nodes must be separate from primary tumor by CT scan or surgical
exploration AND maximum diameter ≤ 3.0 cm

- Mediastinoscopy OR other means of mediastinal lymph node biopsy required
(regardless of the primary tumor site) for patients with subcarinal
lymphadenopathy by size criteria or by positron emission tomography (PET)

- If the lymph nodes in the contralateral mediastinum and neck are visible by
contrast CT scan of the chest AND are ≥ 1.0 cm OR if contralateral
involvement is suggested by PET scan, lymph nodes must be confirmed
negative by one of the above diagnostic procedures AND N3 status must be
confirmed negative by histology or cytology

- No palpable lymph nodes in the supraclavicular areas or higher in the neck
unless proven benign by excisional biopsy

- A nodal biopsy or needle aspiration may be omitted provided all of the
following criteria are true:

- Paralyzed left true vocal cord by bronchoscopy or indirect

- Nodes visible in the aortopulmonary window (level 5) region on CT scan

- Distinct primary tumor (separate from the nodes) is visible by CT scan

- No evidence of subcarinal nodal involvement by CT scan NOTE: **PET
scan positivity is not sufficient to establish N2 nodal status

- Measurable disease by chest x-ray and/or contrast-enhanced CT scan

- Candidate for surgery

- Resectable disease

- No distant metastases, including other ipsilateral or contralateral parenchymal
lesions or liver or adrenal metastases, by history or physical examination,
fludeoxyglucose F 18 PET scan, MRI or CT scan of the brain, chest x-ray and/or CT
scan of the lungs and upper abdomen



- 18 and over

Performance status

- Zubrod 0-1

Life expectancy

- Not specified


- Absolute neutrophil count ≥ 1,800/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)


- ALT and AST ≤ 2.5 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 2.5 times ULN

- Bilirubin ≤ 1.5 times ULN

- No hepatic insufficiency resulting in clinical jaundice or coagulation defects


- Creatinine clearance ≥ 60 mL/min


- No unstable angina or congestive heart failure requiring hospitalization within the
past 6 months

- No transmural myocardial infarction within the past 6 months


- FEV_1 ≥ 2.0 L OR

- Predicted post-resection FEV_1 ≥ 0.8 L

- DLCO ≥ 50% of predicted

- No chronic obstructive pulmonary disease exacerbation

- No other respiratory illness requiring hospitalization or that would preclude study



- No prior allergic reaction to the study drugs

- No history of severe hypersensitivity to other drugs formulated with polysorbate 80

- No acute bacterial or fungal infection requiring IV antibiotics


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No unintentional weight loss > 5% of body weight within the past 6 months

- No pre-existing peripheral neuropathy ≥ grade 2

- No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
or carcinoma in situ of the breast, oral cavity, or cervix

- No other severe active comorbidity


Biologic therapy

- No prior biological agent for this cancer

- No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), or pegfilgrastim during
study induction therapy (for patients randomized to the chemoradiotherapy arm)


- No prior systemic chemotherapy for this cancer

- Prior chemotherapy for a different cancer allowed

Endocrine therapy

- Not specified


- No prior radiotherapy to the region of this cancer that would result in overlap of
radiotherapy fields

- No routine post-operative radiotherapy

- No concurrent intensity modulated radiotherapy


- See Disease Characteristics


- No prior gefitinib for this cancer

- No concurrent amifostine

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Comparison of Overall Survival

Outcome Time Frame:

Date of death or date of last follow-up

Safety Issue:


Principal Investigator

Maria Werner-Wasik, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Kimmel Cancer Center (KCC)


United States: Federal Government

Study ID:




Start Date:

April 2005

Completion Date:

Related Keywords:

  • Lung Cancer
  • stage IIIA non-small cell lung cancer
  • adenocarcinoma of the lung
  • large cell lung cancer
  • squamous cell lung cancer
  • bronchoalveolar cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



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