We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT00750269
Previous Study | Return to List | Next Study

Stereotactic Body Radiation Therapy in Treating Patients With Stage I Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00750269
First Posted: September 10, 2008
Last Update Posted: May 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
  Purpose

RATIONALE: Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue.

PURPOSE: This phase I/II trial is studying the side effects and best dose of stereotactic body radiation therapy and to see how well it works in treating patients with stage I non-small cell lung cancer.


Condition Intervention Phase
Lung Cancer Radiation: SBRT 40.0 Gy Radiation: SBRT 42.5 Gy Radiation: SBRT 45.0 Gy Radiation: SBRT 47.5 Gy Radiation: SBRT 50.0 Gy Radiation: SBRT 52.5 Gy Radiation: SBRT 55.0 Gy Radiation: SBRT 57.5 Gy Radiation: SBRT 60.0 Gy Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Seamless Phase I/II Study of Stereotactic Lung Radiotherapy (SBRT) for Early Stage, Centrally Located, Non-Small Cell Lung Cancer (NSCLC) in Medically Inoperable Patients

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • (Phase I) Maximum Tolerated Dose of Stereotactic Body Radiotherapy (SBRT) as Assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 [ Time Frame: From start of SBRT to 1 year ]
    Maximum tolerated dose (MTD) defined as dose most closely associated with a 20% probability of experiencing a toxicity <= 1 year from start of SBRT from following dose-limiting toxicities: Gr 3-5 Cardiac: Pericardial effusion, Pericarditis, Restrictive cardiomyopathy; Gr 4-5 GI: Dysphagia, Esophagitis, Esophageal fistula/obstruction/perforation/stenosis/ulcer/hemorrhage; Gr 3-5 Nervous System Disorders: Brachial plexopathy, Recurrent laryngeal nerve palsy, Myelitis; Gr 3-5 Respiratory: Atelectasis (gr 4-5 only), Bronchopulmonary/mediastinal/pleural/tracheal hemorrhage, Bronchial/pulmonary/bronchopleural/tracheal fistula, Hypoxia (provided gr 3 is worse than baseline), Bronchial/tracheal obstruction, Pleural effusion, Pneumonitis, Pulmonary fibrosis; Changes in Pulmonary Function Tests per SBRT Pulmonary Toxicity Scale, Gr 3-5: FEV1 decline, FVC decline; Any Gr 5 adverse event attributed to treatment. Dose level was determined by time-to-event continual reassessment method (TITE-CRM).

  • (Phase II) Primary Tumor Control Rate at the Maximum Tolerated Dose (MTD) [ Time Frame: From start of SBRT to 2 years. ]
    Primary tumor control is defined as the absence of primary tumor failure. Primary tumor failure (PTF) refers to the primary treated tumor after protocol therapy and corresponds to meeting following two criteria: 1) Increase in tumor dimension of 20% as defined above for local enlargement (LE); 2) The measurable tumor with criteria meeting LE should be avid on Positron Emission Tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, OR the measurable tumor should be biopsied confirming viable carcinoma. Marginal Failures (MF) and Involved Lobe Failures were also counted as PTF. The cumulative incidence method was used to estimate primary tumor control rate. The 90% confidence interval for local control was calculated using bootstrapping methods. Per the protocol, only the MTD dose level was to be analyzed. However, due to the quantity of patients enrolled on Dose Level 8 as well as safety concerns, Dose Level 8 was analyzed also.


Secondary Outcome Measures:
  • Progression-free Survival [ Time Frame: From randomization to date of death, failure (local, regional or distant) or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study. ]
    Progression-free survival is defined as the state of being alive without progression of disease. A failure is the first of the following: local progression, regional progression, distant metastasis, or death. Progression-free survival was assessed at the maximum tolerated dose using the Kaplan-Meier method to estimate the 2-year survival rate. Arms were not compared/tested.

  • Overall Survival [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study. ]
    An event for overall survival is death due to any cause. Overall survival was assessed at the maximum tolerated dose using the Kaplan-Meier method to estimate the 2-year survival rate. Arms were not compared/tested.

  • Local Progression [ Time Frame: From randomization to date of death, regional failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months. ]
    Local progression is the same as primary tumor failure (PTF) which refers to the primary treated tumor after protocol therapy and corresponds to meeting both of the following two criteria: 1) Increase in tumor dimension of 20% as defined above for local enlargement (LE); 2) The measurable tumor with criteria meeting LE should be avid on Positron Emission Tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, OR the measurable tumor should be biopsied confirming viable carcinoma. For outcome analysis, Marginal Failures (MF) and Involved Lobe Failures will also be counted as PTF. Local progression was assessed using the cumulative incidence method to estimate the 2-year failure rate. Arms were not compared/tested.

  • Nodal Progression [ Time Frame: From randomization to date of death, regional failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study. ]
    Regional nodal progression is defined as appearance after protocol therapy of measurable tumor within lymph nodes along the natural lymphatic drainage typical for the location of the treated primary disease only with dimension of at least 1.0 cm on imaging studies (preferably CT scans) within the lung, bronchial hilum, or the mediastinum. Regional nodal progression was assessed using the cumulative incidence method to estimate the 2-year failure rate. Arms were not compared/tested.

  • Distant Metastases [ Time Frame: From randomization to date of death, distant failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study. ]
    Distant metastases is defined as the appearance after protocol therapy of cancer deposits characteristic of metastatic dissemination from non-small cell lung cancer. Distant metastases progression was assessed using the cumulative incidence method to estimate the 2-year failure rate. Arms were not compared/tested.

  • Rate of Toxicity ≥ Grade 3 (Other Than DLT) Within One Year as Assessed by NCI CTCAE v4.0 [ Time Frame: From start of SBRT until 1 year. ]
    Rate of patients developing any treatment-related toxicity during the first year following the start of SBRT that is not among the types considered as a dose-limiting toxicity.

  • Rate of Late Toxicity (i.e., Occurs > 1 Year After the Start of SBRT) of ≥ Grade 3 as Assessed by NCI CTCAE v4.0 [ Time Frame: From start of treatment to end of follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study. ]
    Percentage of patients who developed any treatment-related toxicity after the first year following the start of SBRT.


Enrollment: 120
Study Start Date: February 2009
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Level 1: 8.0 Gy/FX
SBRT 40.0 Gy
Radiation: SBRT 40.0 Gy
SBRT delivered in 5 fractions of 8.0 Gy/fraction over 1.5 to 2 weeks for a total of 40.0 Gy
Other Names:
  • Stereotactic body radiation therapy (SBRT)
  • Stereotactic ablative radiotherapy (SABR)
Experimental: Level 2: 8.5 Gy/FX
SBRT 42.5 Gy
Radiation: SBRT 42.5 Gy
SBRT delivered in 5 fractions of 8.5 Gy/fraction over 1.5 to 2 weeks for a total of 42.5 Gy
Other Names:
  • Stereotactic body radiation therapy (SBRT)
  • Stereotactic ablative radiotherapy (SABR)
Experimental: Level 3: 9.0 Gy/FX
SBRT 45.0 Gy
Radiation: SBRT 45.0 Gy
SBRT delivered in 5 fractions of 9.0 Gy/fraction over 1.5 to 2 weeks for a total of 45.0 Gy
Other Names:
  • Stereotactic body radiation therapy (SBRT)
  • Stereotactic ablative radiotherapy (SABR)
Experimental: Level 4: 9.5 Gy/FX
SBRT 47.5 Gy
Radiation: SBRT 47.5 Gy
SBRT delivered in 5 fractions of 9.5 Gy/fraction over 1.5 to 2 weeks for a total of 47.5 Gy
Other Names:
  • Stereotactic body radiation therapy (SBRT)
  • Stereotactic ablative radiotherapy (SABR)
Experimental: Level 5: 10.0 Gy/FX
SBRT 50.0 Gy
Radiation: SBRT 50.0 Gy
SBRT delivered in 5 fractions of 10.0 Gy/fraction over 1.5 to 2 weeks for a total of 50.0 Gy
Other Names:
  • Stereotactic body radiation therapy (SBRT)
  • Stereotactic ablative radiotherapy (SABR)
Experimental: Level 6: 10.5 Gy/FX
SBRT 52.5 Gy
Radiation: SBRT 52.5 Gy
SBRT delivered in 5 fractions of 10.5 Gy/fraction over 1.5 to 2 weeks for a total of 52.5 Gy
Other Names:
  • Stereotactic body radiation therapy (SBRT)
  • Stereotactic ablative radiotherapy (SABR)
Experimental: Level 7: 11.0 Gy/FX
SBRT 55.0 Gy
Radiation: SBRT 55.0 Gy
SBRT delivered in 5 fractions of 11.0 Gy/fraction over 1.5 to 2 weeks for a total of 55.0 Gy
Other Names:
  • Stereotactic body radiation therapy (SBRT)
  • Stereotactic ablative radiotherapy (SABR)
Experimental: Level 8: 11.5 Gy/FX
SBRT 57.5 Gy
Radiation: SBRT 57.5 Gy
SBRT delivered in 5 fractions of 11.5 Gy/fraction over 1.5 to 2 weeks for a total of 57.5 Gy
Other Names:
  • Stereotactic body radiation therapy (SBRT)
  • Stereotactic ablative radiotherapy (SABR)
Experimental: Level 9: 12.0 Gy/FX
SBRT 60.0 Gy
Radiation: SBRT 60.0 Gy
SBRT delivered in 5 fractions of 12.0 Gy/fraction over 1.5 to 2 weeks for a total of 60.0 Gy
Other Names:
  • Stereotactic body radiation therapy (SBRT)
  • Stereotactic ablative radiotherapy (SABR)

Detailed Description:

OBJECTIVES:

Primary

  • To determine the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) in medically inoperable patients with centrally located stage I non-small cell lung cancer. (Phase I)
  • To estimate the local control rate of SBRT at the MTD in these patients. (Phase II)

Secondary

  • To estimate the rates of adverse events (other than dose-limiting toxicity) of ≥ grade 3 that is possibly, probably, or definitely related to treatment and that occurs within 1 year after the start of SBRT in these patients.
  • To estimate the rates of late adverse events (i.e., occurs > 1 year after the start of SBRT) in these patients.
  • To estimate the local control and progression-free and overall survival rates in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients undergo stereotactic body radiotherapy every 2 days over 1½-2 weeks [total of 5 fractions (FX)] in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 2 years, then every 6 months for 2 years, then annually.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

    • Stage T1-2, N0, M0 disease

      • Tumor size ≤ 5 cm
      • Tumor must be within or touching the zone of the proximal bronchial tree, defined as a volume of 2 cm in all directions around the proximal bronchial tree (i.e., carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus right, and left lower lobe bronchi) OR immediately adjacent to the mediastinal or pericardial pleura (PTV touching the pleura)
      • Hilar or mediastinal lymph nodes ≤ 1 cm AND no abnormal hilar or mediastinal uptake on positron emission tomography (PET) scan are considered N0

        • Mediastinal lymph node sampling by any technique is allowed but not required
        • Patients with > 1 cm hilar or mediastinal lymph nodes on CT scan or abnormal PET scan (including suspicious but nondiagnostic uptake) are eligible provided directed tissue biopsies of all abnormally identified areas are negative for cancer
  • Tumor deemed technically resectable, in the opinion of an experienced thoracic cancer surgeon, with a reasonable possibility of obtaining a gross total resection with negative margins, defined as a potentially curative resection (PCR)
  • Patient deemed "medically inoperable" due to severe underlying physiological medical problems that would prohibit a PCR, including any of the following:

    • Baseline forced expiratory volume at one second (FEV1) < 40% predicted
    • Postoperative FEV1 < 30% predicted
    • Severely reduced diffusion capacity
    • Baseline hypoxemia and/or hypercapnia
    • Exercise oxygen consumption < 50% predicted
    • Severe pulmonary hypertension
    • Diabetes mellitus with severe end-stage organ damage
    • Severe cerebral, cardiac, or peripheral vascular disease
    • Severe chronic heart disease
  • Measurable disease as documented by CT scan or whole-body PET scan within the past 8 weeks

    • Patients with lesions that cannot be visualized by CT scan are not eligible
  • Pleural effusion allowed provided it is deemed too small to tap under CT guidance and is not evident on chest x-ray

    • Pleural effusion that appears on chest x-ray is allowed only after thoracotomy or other invasive procedure

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-2
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 60 days after completion of study therapy
  • No other invasive malignancy within the past 2 years except nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix

    • Prior lung cancer allowed provided the patient has been disease-free for ≥ 2 years

PRIOR CONCURRENT THERAPY:

  • No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
  • No prior chemotherapy for the study cancer
  • No other concurrent local therapy (including standard-fractionated radiotherapy and/or surgery) or systemic therapy (including standard chemotherapy or biologic targeted agents) specifically intended as treatment for study cancer

    • Local or systemic therapy at the time of disease progression allowed
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00750269


  Show 58 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
Investigators
Principal Investigator: Andrea Bezjak, MD, MSC, FRCPC Princess Margaret Hospital, Canada
Study Chair: Jeffrey Bradley, MD Mallinckrodt Institute of Radiology at Washington University Medical Center
Study Chair: Laurie E. Gaspar, MD, MBA University of Colorado, Denver
Study Chair: Robert D. Timmerman, MD University of Texas
Study Chair: Elizabeth Gore, MD Medical College of Wisconsin
Study Chair: Feng-Ming Phoenix Konb, MD, PhD Georgia Regents University Cancer Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00750269     History of Changes
Obsolete Identifiers: NCT01317056
Other Study ID Numbers: RTOG-0813
CDR0000613524
NCI-2009-01095 ( Registry Identifier: CTRP (Clinical Trials Reporting Program) )
First Submitted: September 9, 2008
First Posted: September 10, 2008
Results First Submitted: June 30, 2016
Results First Posted: May 10, 2017
Last Update Posted: May 10, 2017
Last Verified: March 2017

Keywords provided by Radiation Therapy Oncology Group:
stage I non-small cell lung cancer

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