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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

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ClinicalTrials.gov Identifier: NCT01336894
Recruitment Status : Terminated (recruiting or enrolling participants has halted prematurely and will not resume; participants are no longer being examined or treated)
First Posted : April 18, 2011
Results First Posted : March 28, 2017
Last Update Posted : May 30, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE April 15, 2011
First Posted Date  ICMJE April 18, 2011
Results First Submitted Date  ICMJE November 28, 2016
Results First Posted Date  ICMJE March 28, 2017
Last Update Posted Date May 30, 2017
Study Start Date  ICMJE May 2011
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2017)
3-year Overall Survival (OS) Rate [ Time Frame: Up to 3 years post-randomization ]
Overall survival is defined as the time from randomization until death from any cause.
Original Primary Outcome Measures  ICMJE
 (submitted: April 15, 2011)
5-year OS rate
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2017)
  • Loco-regional Recurrence-free Survival [ Time Frame: Up to 5 years post-randomization ]
    Loco-regional recurrence is defined as recurrence within the same lobe or hilum (N1 nodes), or within 2 cm of the staple line or within 2 cm of the PTV after treatment effects such as scarring have subsided.
  • Adverse Event Profiles at 1 Month Post-therapy [ Time Frame: 1 month post-therapy ]
    Adverse events are described and graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death.
  • Adverse Event Profiles at 3 Months Post-therapy [ Time Frame: 3 months post-therapy ]
    Adverse events are described and graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death.
  • Adverse Event Profiles at 12 Months Post-therapy [ Time Frame: 12 months post-therapy ]
    Adverse events are described and graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death.
  • Disease-free Survival [ Time Frame: Up to 5 years post-randomization ]
    Disease free survival is defined as the time from randomization until documented disease recurrence or death, whichever occurs first. Patient who are disease free and alive at the time of analysis will be censored at the time of their last follow up.
  • Pulmonary Function Test Values [ Time Frame: Up to 12 months post-therapy ]
    Pulmonary function test values include forced expiratory volume 1 (FEV1), carbon monoxide diffusion (DLCO) and forced vital capacity (FVC).
Original Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2011)
  • Loco-regional Recurrence-free Survival
  • Adverse event profiles at 1, 3, 6, and 12 months post-therapy
  • Disease-free Survival
  • Pulmonary Function Test Values
  • Overall quality of life
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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)
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lung Cancer
Intervention  ICMJE
  • Procedure: therapeutic conventional surgery
    Undergo surgery
  • Radiation: iodine I 125
    Undergo seed implant radiotherapy
  • Radiation: stereotactic body radiation therapy
    Undergo radiotherapy
Study Arms  ICMJE
  • Active Comparator: Arm I (SR+Brachytherapy)
    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.
    Interventions:
    • Procedure: therapeutic conventional surgery
    • Radiation: iodine I 125
  • Experimental: Arm II (SBRT)
    Patients undergo 3 fractions of stereotactic body radiation therapy at 2-8 days apart.
    Intervention: Radiation: stereotactic body radiation therapy
Publications * Fernando HC, Timmerman R. American College of Surgeons Oncology Group Z4099/Radiation Therapy Oncology Group 1021: a randomized study of sublobar resection compared with stereotactic body radiotherapy for high-risk stage I non-small cell lung cancer. J Thorac Cardiovasc Surg. 2012 Sep;144(3):S35-8. doi: 10.1016/j.jtcvs.2012.06.003. Epub 2012 Jul 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 31, 2015)
13
Original Estimated Enrollment  ICMJE
 (submitted: April 15, 2011)
420
Actual Study Completion Date  ICMJE March 27, 2017
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01336894
Other Study ID Numbers  ICMJE Z4099
U10CA076001 ( U.S. NIH Grant/Contract )
NCI-2011-02667 ( Registry Identifier: NCI Clinical Trials Reporting Office )
CDR0000698986 ( Registry Identifier: Physician Data Query )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Hiran C. Fernando, MD Boston Medical Center
PRS Account Alliance for Clinical Trials in Oncology
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP