Surgery With or Without Internal Radiation Therapy Compared With Stereotactic Body Radiation Therapy in Treating Patients With High-Risk Stage I Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01336894
First received: April 15, 2011
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

RATIONALE: Surgery with or without internal radiation therapy may be an effective treatment for non-small cell lung cancer. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. It is not yet known whether stereotactic body radiation therapy is more effective than surgery with or without internal radiation therapy in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying how well surgery with or without internal radiation therapy works compared with stereotactic body radiation therapy in treating patients with high-risk stage IA or stage IB non-small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Procedure: therapeutic conventional surgery
Radiation: iodine I 125
Radiation: stereotactic body radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Study of Sublobar Resection (+/- Brachytherapy) Versus Stereotactic Body Radiation Therapy in High Risk Patients With Stage I Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • 5-year OS rate [ Time Frame: Up to 5 years post-randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Loco-regional recurrence-free survival [ Time Frame: Up to 5 years post-randomization ] [ Designated as safety issue: No ]
  • Adverse event profiles at 1, 3, 6, and 12 months post-therapy [ Time Frame: Up to 12 months post-therapy ] [ Designated as safety issue: Yes ]
  • Disease-free survival [ Time Frame: Up to 5 years post-randomization ] [ Designated as safety issue: No ]
  • Pulmonary function test values [ Time Frame: Up to 12 months post-therapy ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 420
Study Start Date: May 2011
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients undergo sublobar resection comprising either a wedge resection or anatomical segmentectomy with or without intraoperative brachytherapy comprising an iodine I 125 implant at the resection margin.
Procedure: therapeutic conventional surgery
Undergo surgery
Radiation: iodine I 125
Undergo seed implant radiotherapy
Experimental: Arm II
Patients undergo 3 fractions of stereotactic body radiation therapy at 2-8 days apart.
Radiation: stereotactic body radiation therapy
Undergo radiotherapy

  Hide Detailed Description

Detailed Description:

OBJECTIVES:

Primary

  • To ascertain whether patients treated by stereotactic body radiation therapy (SBRT) have a 3-year overall survival (OS) rate that is no more than 10% less than patients treated with sublobar resection (SR).

Secondary

  • To compare loco-regional recurrence-free survival between study arms.
  • To compare disease-free survival between study arms.
  • To compare grade 3 or higher specific adverse event profiles between study arms at 1, 3, 6, and 12 months post-therapy.
  • To compare pulmonary function between patients treated with SBRT and patients treated with SR.
  • To compare the adverse events and pulmonary function tests (PFTs) in each arm for patients with low or high Charlson comorbidity index scores, including a test interaction between Charlson comorbidity index scores (low vs high) and treatment arm.

Tertiary

  • To compare the quality-adjusted survival between the SBRT and SR treatments in terms of time to death (primary) and time until recurrence (secondary).
  • To examine whether pre-operative and post-operative clinically significant deficits in previously identified prognostic PRO domains (overall quality of life [QOL], fatigue, anxiety, and dyspnea) are associated with shorter patient survival in this patient population and to compare the relative effectiveness of each treatment (SBRT and SR).
  • To contribute to an ACOSOG bank of normative data in order to improve short/long-term outcomes of cancer patients by identifying patients experiencing clinically significant deficits in patient-reported outcomes and the relationship to genetic variables.
  • To explore whether blood-based biomarkers, including osteopontins, will be able to predict which patients will be at high risk for recurrence by treatment with either SBRT or SR. (exploratory)
  • To explore whether blood-based biomarkers, including TGF-β1, will be able to predict which patients will be at high risk for pulmonary complications by treatment with either SBRT or SR. (exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to planned brachytherapy (yes vs no) and ECOG performance status (0 vs 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo sublobar resection comprising either a wedge resection or anatomical segmentectomy with or without intraoperative brachytherapy* comprising an iodine I 125 implant at the resection margin.
  • Arm II: Patients undergo 3 fractions of stereotactic body radiation therapy at 2-8 days apart.

NOTE: *Patients may receive brachytherapy at the discretion of treating physician.

Patients may undergo blood sample collection at baseline and periodically during study for correlative studies. Tumor tissue samples may also be collected from patients who undergo resection.

Patients complete the Lung Cancer Symptom Scale (LCSS), the Linear Analogue Self-Assessment (LASA), and the UCDS Shortness of Breath quality-of-life questionnaires at baseline and periodically during study and follow-up.

After completion of study treatment, patients are followed up for 30 days, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 2 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Lung nodule suspicious for non-small cell lung cancer (NSCLC)

    • Biopsy confirmation is strongly recommended but not required; if biopsy is attempted and non-diagnostic, if the patient refuses biopsy, or if the risk of biopsy is considered too high, patients may be enrolled if the mass is suspicious for NSCLC based on two or more of the following criteria:

      • Positive smoking history
      • Absence of benign calcifications within suspicious nodule
      • Activity on PET greater than normal tissue
      • Evidence of growth compared to previous imaging
      • Presence of spiculation
  • Tumor ≤ 4 cm maximum diameter, clinical stage IA or selected IB (i.e., with visceral pleural involvement) by PET/CT scan of the chest and upper abdomen performed within 60 days prior to registration
  • All clinically suspicious mediastinal N1, N2, or N3 lymph nodes (> 1 cm short-axis dimension on CT scan and/or positive on PET scan) confirmed negative for involvement with NSCLC by one of the following methods: mediastinoscopy, anterior mediastinotomy, endoscopic and/or endobronchial ultrasonography (EUS/EBUS)-guided needle aspiration, CT-guided, or video-assisted thoracoscopic or open lymph node biopsy
  • Tumor verified by a thoracic surgeon to be in a location that will permit sublobar resection
  • Tumor located peripherally within the lung, defined as not touching any surface within 2 cm of the proximal bronchial tree in all directions

    • Patients with non-peripheral (central) tumors are NOT eligible
  • No evidence of distant metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0, 1, or 2
  • Patient at high-risk for surgery by meeting a minimum of one major criteria or two minor criteria as described below:

    • Major criteria

      • FEV1 ≤ 50% predicted
      • DLCO ≤ 50% predicted
    • Minor criteria

      • Age ≥ 75 years
      • FEV1 51-60% predicted
      • DLCO 51-60% predicted
      • Pulmonary hypertension (defined as a pulmonary artery systolic pressure greater than 40 mm Hg) as estimated by echocardiography or right heart catheterization
      • Poor left ventricular function (defined as an ejection fraction of 40% or less)
      • Resting or exercise arterial pO2 ≤ 55 mm Hg or SpO2 ≤ 88%
      • pCO2 > 45 mm Hg
      • Modified Medical Research Council (MMRC) Dyspnea Scale ≥ 3
  • Not pregnant or nursing
  • Negative urine or serum pregnancy test
  • Fertile patients must use effective contraception
  • No prior invasive malignancy, unless disease-free for ≥ 3 years prior to registration (except non-melanoma skin cancer, in-situ cancers).

PRIOR CONCURRENT THERAPY:

  • No prior intra-thoracic radiotherapy

    • Prior radiotherapy as part of treatment for head and neck, breast, or other non-thoracic cancer is permitted
  • Prior chemotherapy or surgical resection for the lung cancer being treated on this protocol is NOT permitted
  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: NCT01336894

  Show 53 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Principal Investigator: Hiran C. Fernando, MD Boston Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01336894     History of Changes
Other Study ID Numbers: Z4099, U10CA076001, NCI-2011-02667, CDR0000698986
Study First Received: April 15, 2011
Last Updated: May 20, 2014
Health Authority: United States: Central Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
stage IA non-small cell lung cancer
stage IB non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 16, 2014