Radiation Therapy in Treating Patients With Non Small Cell Lung Cancer That Has Been Completely Removed by Surgery (LUNG ART)

• ClinicalTrials.gov Identifier: NCT00410683
• Recruitment Status: Unknown
• First Posted: December 13, 2006
• Last Update Posted: November 20, 2020
• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris
• Collaborators: Intergroupe Francophone de Cancerologie Thoracique; The Christie NHS Foundation Trust; European Organisation for Research and Treatment of Cancer - EORTC
• Information provided by (Responsible Party): Gustave Roussy, Cancer Campus, Grand Paris

Tracking Information

• First Submitted Date: December 11, 2006
• First Posted Date: December 13, 2006
• Last Update Posted Date: November 20, 2020
• Actual Study Start Date: February 2007
• Actual Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 13, 2013): Disease-free survival (DFS) [ Time Frame: assessed up every 3 and 6 months after randomization, every 6 months for the fist three years and yearly afterward ]
• Original Primary Outcome Measures (submitted: December 11, 2006): Disease-free survival (DFS)

Current Secondary Outcome Measures (submitted: June 13, 2013)

• Acute and late toxicity (with identification of predictive factors of toxicity) [ Time Frame: assessed up at 3 and 6 months after randomization and then yearly afterward; And in case of event ]
• Local control [ Time Frame: assessed up at 3 and 6 months after randomization and then yearly afterward; And in case of event ]
• Patterns of failure [ Time Frame: assessed up at 3 and 6 months after randomization and then yearly afterward; And in case of event ]
• Overall survival (OS) [ Time Frame: assessed up In case of death whatever the cause ]
• Second cancers [ Time Frame: Assessed up in case of event ]
• Prognostic and predictive factors of treatment effect on DFS and OS [ Time Frame: assessed up at the end of the study ]
• Cost per recurrence-free year of life [ Time Frame: Assessed up at the end of the study ]

Original Secondary Outcome Measures (submitted: December 11, 2006)

• Acute and late toxicity (with identification of predictive factors of toxicity)
• Local control
• Patterns of recurrence
• Overall survival (OS)
• Second cancers
• Prognostic and predictive factors of DFS and OS
• Cost per recurrence-free year of life

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Radiation Therapy in Treating Patients With Non Small Cell Lung Cancer That Has Been Completely Removed by Surgery
• Official Title: Phase III Study Comparing Post-Operative Conformal Radiotherapy to No Post-Operative Radiotherapy in Patients With Completely Resected Non-Small Cell Lung Cancer and Mediastinal N2 Involvement [Lung ART]

Brief Summary

RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving radiation therapy after surgery is more effective than no radiation therapy in treating patients with non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared to no radiation therapy in treating patients with non-small cell lung cancer that has been completely removed by surgery.

Detailed Description

OBJECTIVES:

Primary

• Compare the disease-free survival of patients with completely resected non-small cell lung cancer treated with conformal thoracic radiotherapy vs no radiotherapy.

Secondary

• Determine the toxicity, in particular cardiac and pulmonary toxicity, of these regimens in these patients.
• Compare the local control in patients treated with these regimens.
• Determine patterns of recurrence in patients treated with these regimens.
• Determine the overall survival of patients treated with these regimens.
• Assess second cancers in patients treated with these regimens.
• Assess prognostic factors and predictive factors of treatment effect on disease-free survival and overall survival of patients treated with these regimens.
• Determine the cost per recurrence-free year of life.

OUTLINE: This is a multicenter, randomized study.

Patients are stratified according to participating center, prior chemotherapy (neoadjuvant alone vs adjuvant vs none), number of lymph stations involved (0 vs 1 vs ≥ 2), histology (squamous cell vs other), and use of pretreatment positron emission tomography scans (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Beginning within 4-8 weeks after surgery or 2-6 weeks after chemotherapy, patients undergo adjuvant thoracic conformal radiotherapy once daily, 5 days per week, for 6 weeks.
• Arm II: Patients do not undergo adjuvant thoracic radiotherapy. After completion of study therapy, patients are followed periodically for up to10 years.

PROJECTED ACCRUAL: A total of 700 patients will be accrued for this study.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer

Intervention

• Other: clinical observation
• Procedure: adjuvant therapy
• Radiation: 3-dimensional conformal radiation therapy

Study Arms

• Experimental: Radiotherapy
  Beginning within 4-8 weeks after surgery or 2-6 weeks after chemotherapy, patients undergo adjuvant thoracic conformal radiotherapy once daily, 5 days per week, for 6 weeks.
  Interventions:

  • Other: clinical observation
  • Procedure: adjuvant therapy
  • Radiation: 3-dimensional conformal radiation therapy
• Active Comparator: No radiotherapy
  Patients do not undergo adjuvant thoracic radiotherapy. After completion of study therapy, patients are followed periodically for up to 10 years.
  Interventions:

  • Other: clinical observation
  • Procedure: adjuvant therapy

• Publications *: Le Pechoux C, Pourel N, Barlesi F, Lerouge D, Antoni D, Lamezec B, Nestle U, Boisselier P, Dansin E, Paumier A, Peignaux K, Thillays F, Zalcman G, Madelaine J, Pichon E, Larrouy A, Lavole A, Argo-Leignel D, Derollez M, Faivre-Finn C, Hatton MQ, Riesterer O, Bouvier-Morel E, Dunant A, Edwards JG, Thomas PA, Mercier O, Bardet A. Postoperative radiotherapy versus no postoperative radiotherapy in patients with completely resected non-small-cell lung cancer and proven mediastinal N2 involvement (Lung ART): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Jan;23(1):104-114. doi: 10.1016/S1470-2045(21)00606-9. Epub 2021 Dec 15. Erratum In: Lancet Oncol. 2022 Jul;23(7):e319.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 7, 2017): 500
• Original Enrollment (submitted: December 11, 2006): 700
• Estimated Study Completion Date: February 2022
• Actual Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

INCLUSION CRITERIA :

1. Histological evidence of non-small cell lung cancer (NSCLC)
2. Complete resection by lobectomy, bilobectomy or pneumonectomy (i.e patients with positive margins) or extra-capsular mediastinal nodal extension breaching the surface of the pathological specimen should not to be included
3. Mediastinal lymph node exploration (lymph node sampling or systematic dissection of lymph nodes at stations 2, 4 and 7 in case of upper/middle right-sided lung cancer; 4, 7, 8 and 9 in case of lower right-sided lung cancer; 5, 6 and 7 in case of upper left -sided lung cancer; 7, 8 and 9 in case of lower left-sided lung cancer is recommended)
4. Pathologically or cytologically documented N2 mediastinal nodal involvement, at the time of surgery if no preoperative chemotherapy or before preoperative chemotherapy, according to the criteria of the joint AJCC and UICC classification, clinical N2 patients without cytological or histological documentation of mediastinal node involvement before preoperative chemotherapy can be included in the study if and only if, they have histologically confirmed N2 disease at the time of surgery
5. Prior chemotherapy is allowed (pre-operative or post-operative adjuvant chemotherapy, or both)
6. Patient aged ≥ 18 years
7. Good Performance status (WHO ≤ 2)
8. Fit enough to receive curative radiotherapy
9. Adequate pulmonary function with post-operative FEV1 after surgery > 1 l or over 35% theoretical value
10. Signed informed consent form

EXCLUSION CRITERIA:

1. Documented metastases, (except for ipsilateral nodule(s) in a different lobe after pneumonectomy or bi-lobectomy)
2. Major pleural or pericardial effusion
3. Synchronous contra-lateral lung cancer
4. Clinical progression during post-operative chemotherapy
5. Previous chest radiotherapy
6. Intention of concomitant chemotherapy during radiotherapy
7. Weight loss in the previous 6 months before surgery ≥ 10 %
8. Evidence of severe or uncontrolled systemic disease as judged by the investigator
9. Recent (< 6 months) severe cardiac disease (arrhythmia, congestive heart failure, infarction, pace-maker) or pulmonary disease

10. Current or past history of neoplasm other than non-small cell lung cancer diagnosed within the last 5 years, except :

    • basal cell carcinoma of the skin
    • in situ carcinoma of the cervix A patient diagnosed for another neoplasm 5 years ago or more, treated and considered as cured may be included in the study if all the other criteria are respected.
11. Pregnancy or breast feeding or inadequate contraceptive measures during treatment
12. Patients who, for family, social, geographic or psychological reasons, cannot be adequately followed up and/or are incapable of undergoing regular controls
13. Patient deprived of freedom or under guardianship

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00410683
• Other Study ID Numbers: CDR0000523568; 2006/1202 ( Other Identifier: CSET number ); PROTEGE-01/0601 ( Other Identifier: UNICANCER ); 20671 ( Other Identifier: European Union ); IFCT - 0503 ( Other Identifier: IFCT ); UK11/NW/0075 ( Other Identifier: The Christie NHS Foundation Trust )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
• Original Responsible Party: Not Provided
• Current Study Sponsor: Gustave Roussy, Cancer Campus, Grand Paris
• Original Study Sponsor: UNICANCER

Collaborators

• Intergroupe Francophone de Cancerologie Thoracique
• The Christie NHS Foundation Trust
• European Organisation for Research and Treatment of Cancer - EORTC

Investigators

• Study Chair: Cecile Le Pechoux, MD; Gustave Roussy, Cancer Campus, Grand Paris

• PRS Account: Gustave Roussy, Cancer Campus, Grand Paris
• Verification Date: November 2020