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Lung CancerPhase 3NCT01336894

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

A Phase 3 study testing therapeutic conventional surgery, iodine I 125 and stereotactic body radiation therapy in people with Lung Cancer, run by Alliance for Clinical Trials in Oncology at 53 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Cancer
What is being tested?
therapeutic conventional surgery, iodine I 125 and stereotactic body radiation therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
53 sitesin 2 countries
Study dates
May 2011to 27 Mar 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

53 sites in 2 countries.

53 sites in 2 countries

United States49 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109-0942

  • DeCesaris Cancer Institute at Anne Arundel Medical Center

    Annapolis, Maryland, 21401

  • Emory Crawford Long Hospital

    Atlanta, Georgia, 30308

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • Greenebaum Cancer Center at University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • St. Agnes Hospital Cancer Center

    Baltimore, Maryland, 21229

  • UAB Comprehensive Cancer Center

    Birmingham, Alabama, 35294

  • Tufts Medical Center Cancer Center

    Boston, Massachusetts, 02111

  • Boston University Cancer Research Center

    Boston, Massachusetts, 02118

  • Hollings Cancer Center at Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • University of Chicago Cancer Research Center

    Chicago, Illinois, 60637-1470

  • Charles M. Barrett Cancer Center at University Hospital

    Cincinnati, Ohio, 45267

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210-1240

  • Baylor University Medical Center - Dallas

    Dallas, Texas, 75246

  • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390

  • Geisinger Cancer Institute at Geisinger Health

    Danville, Pennsylvania, 17822-0001

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Baptist Cancer Institute - Jacksonville

    Jacksonville, Florida, 32207

  • Gundersen Lutheran Center for Cancer and Blood

    La Crosse, Wisconsin, 54601

  • Lucille P. Markey Cancer Center at University of Kentucky

    Lexington, Kentucky, 40536-0093

  • James Graham Brown Cancer Center at University of Louisville

    Louisville, Kentucky, 40202

  • Medical College of Wisconsin Cancer Center

    Milwaukee, Wisconsin, 53226

  • Veterans Affairs Medical Center - Milwaukee

    Milwaukee, Wisconsin, 53295

  • St. Luke's - Roosevelt Hospital Center - St.Luke's Division

    New York, New York, 10025

  • Sentara Cancer Institute at Sentara Norfolk General Hospital

    Norfolk, Virginia, 23507

  • M.D. Anderson Cancer Center at Orlando

    Orlando, Florida, 32806

  • OSF St. Francis Medical Center

    Peoria, Illinois, 61637

  • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

    Philadelphia, Pennsylvania, 19107-5541

  • Mayo Clinic Hospital

    Phoenix, Arizona, 85054

  • Allegheny Cancer Center at Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • Providence Cancer Center at Providence Portland Medical Center

    Portland, Oregon, 97213-2967

  • Valley Hospital - Ridgewood

    Ridgewood, New Jersey, 07450

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • James P. Wilmot Cancer Center at University of Rochester Medical Center

    Rochester, New York, 14642

  • William Beaumont Hospital - Royal Oak Campus

    Royal Oak, Michigan, 48073

  • University of California Davis Cancer Center

    Sacramento, California, 95817

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

    Savannah, Georgia, 31403-3089

  • Mayo Clinic Scottsdale

    Scottsdale, Arizona, 85259-5499

  • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

    Seattle, Washington, 98122-4307

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St Louis, Missouri, 63110

  • Stanford Cancer Center

    Stanford, California, 94305-5824

  • Stony Brook University Cancer Center

    Stony Brook, New York, 11794-9446

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

  • Waukesha Memorial Hospital Regional Cancer Center

    Waukesha, Wisconsin, 53188

  • Wake Forest University Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157-1096

  • York Cancer Center at Apple Hill Medical Center

    York, Pennsylvania, 17405

Other trials in United States

Canada4 sites

  • London Regional Cancer Program at London Health Sciences Centre

    London, Ontario, N6A 4L6

  • Hopital Notre-Dame du CHUM

    Montreal, Quebec, H2L 4M1

  • Ottawa Hospital Regional Cancer Centre - General Campus

    Ottawa, Ontario, K1Y 4E9

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

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)

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.

Read the 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.

Conditions
Lung Cancer
Being tested
therapeutic conventional surgery, iodine I 125, stereotactic body radiation therapy
Keywords
stage IA non-small cell lung cancer, stage IB non-small cell lung cancer
Medical subject headings
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • therapeutic conventional surgeryProcedure or surgery

    Undergo surgery

  • iodine I 125Radiation

    Undergo seed implant radiotherapy

  • stereotactic body radiation therapyRadiation

    Undergo radiotherapy

Study groups in NCT01336894
Study groupRoleWhat they receive
Arm I (SR+Brachytherapy)Active comparatorPatients 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.
Receives: Procedure: therapeutic conventional surgery; Radiation: iodine I 125
Arm II (SBRT)ExperimentalPatients undergo 3 fractions of stereotactic body radiation therapy at 2-8 days apart.
Receives: Radiation: stereotactic body radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 3-year Overall Survival (OS) Rate

    Overall survival is defined as the time from randomization until death from any cause.

    Measured: Up to 3 years post-randomization

Secondary outcomes (6)

  1. Loco-regional Recurrence-free Survival

    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.

    Measured: Up to 5 years post-randomization

  2. Adverse Event Profiles at 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.

    Measured: 1 month post-therapy

  3. Adverse Event Profiles at 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.

    Measured: 3 months post-therapy

  4. Adverse Event Profiles at 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.

    Measured: 12 months post-therapy

  5. Disease-free Survival

    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.

    Measured: Up to 5 years post-randomization

  6. Pulmonary Function Test Values

    Pulmonary function test values include forced expiratory volume 1 (FEV1), carbon monoxide diffusion (DLCO) and forced vital capacity (FVC).

    Measured: Up to 12 months post-therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Apr 2011 (estimated)
  2. Study startMay 2011
  3. Primary completionMay 2013
  4. Study completion27 Mar 2017

Why it stopped: recruiting or enrolling participants has halted prematurely and will not resume; participants are no longer being examined or treated

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01336894
Sponsor's protocol ID
Z4099
Other IDs
U10CA076001, NCI-2011-02667, CDR0000698986
Status last verified
Apr 2017
First submitted
15 Apr 2011
Last updated
30 May 2017
Data monitoring committee
Yes

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.

    PubMed 22795435

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing therapeutic conventional surgery, iodine I 125 and stereotactic body radiation therapy in people with Lung Cancer, run by Alliance for Clinical Trials in Oncology at 53 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

3-year Overall Survival (OS) Rate (time frame: Up to 3 years post-randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01336894, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2017.

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