Cisplatin and Docetaxel With or Without Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Newly Diagnosed Stage III Non-Small Cell Lung Cancer

This study has been terminated.
(This study terminated early due to low accrual.)
Sponsor:
Collaborators:
Southwest Oncology Group
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
North Central Cancer Treatment Group
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00113386
First received: June 7, 2005
Last updated: June 21, 2013
Last verified: June 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Cisplatin and docetaxel may make tumor cells more sensitive to radiation therapy. Giving more than one drug (combination chemotherapy) together with radiation therapy before surgery may shrink the tumor so it can be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving cisplatin and docetaxel together with radiation therapy is more effective than giving cisplatin together with docetaxel in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying cisplatin, docetaxel, and radiation therapy to see how well they work compared to cisplatin and docetaxel in treating patients who are undergoing surgery for newly diagnosed stage III non-small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Biological: filgrastim
Biological: pegfilgrastim
Drug: cisplatin
Drug: docetaxel
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Comparison of Overall Survival [ Time Frame: Date of death or date of last follow-up ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: April 2005
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Induction chemotherapy, surgery, consolidation chemotherapy
Induction/surgery/consolidation
Biological: filgrastim
Consolidation chemotherapy
Biological: pegfilgrastim
Consolidation chemotherapy
Drug: cisplatin Drug: docetaxel Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy
Chemotherapy and radiation, surgery, consolidation ch
Induction/radiation/surgery/cosolidation
Biological: filgrastim
Consolidation chemotherapy
Biological: pegfilgrastim
Consolidation chemotherapy
Drug: cisplatin Drug: docetaxel Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy

Detailed Description:

OBJECTIVES:

Primary

  • 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 docetaxel.

Secondary

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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 guidance

      • 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) scan
      • 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 laryngoscopy
        • 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

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,800/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)

Hepatic

  • 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

Renal

  • Creatinine clearance ≥ 60 mL/min

Cardiovascular

  • No unstable angina or congestive heart failure requiring hospitalization within the past 6 months
  • No transmural myocardial infarction within the past 6 months

Pulmonary

  • 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 therapy

Immunologic

  • No AIDS
  • 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

Other

  • 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

PRIOR CONCURRENT THERAPY:

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)

Chemotherapy

  • No prior systemic chemotherapy for this cancer

    • Prior chemotherapy for a different cancer allowed

Endocrine therapy

  • Not specified

Radiotherapy

  • 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

Surgery

  • See Disease Characteristics

Other

  • No prior gefitinib for this cancer
  • No concurrent amifostine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00113386

  Show 76 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Southwest Oncology Group
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
North Central Cancer Treatment Group
Investigators
Principal Investigator: Maria Werner-Wasik, MD Kimmel Cancer Center (KCC)
Principal Investigator: Howard L. West, MD Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
Study Chair: Jeffrey Crawford, MD Duke Cancer Institute
Study Chair: Chandra P. Belani, MD University of Pittsburgh
Study Chair: James R. Jett, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00113386     History of Changes
Other Study ID Numbers: RTOG-0412, CDR0000429479, SWOG-S0332, CALGB-RTOG-0412, ECOG-RTOG-0412, NCCTG-RTOG-0412
Study First Received: June 7, 2005
Results First Received: November 27, 2012
Last Updated: June 21, 2013
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
stage IIIA non-small cell lung cancer
adenocarcinoma of the lung
large cell lung cancer
squamous cell lung cancer
bronchoalveolar cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Cisplatin
Docetaxel
Antimitotic Agents
Antineoplastic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 22, 2014