Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

To Evaluate the Role of Postoperative Radiotherapy in Patients With IIIA(N2) Non-Small Cell Lung Cancer

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02977169
Recruitment Status : Recruiting
First Posted : November 30, 2016
Last Update Posted : November 13, 2020
Sponsor:
Information provided by (Responsible Party):
Xiaolong Fu, Shanghai Chest Hospital

Brief Summary:

Rationale: Completely resected non-small cell lung cancer (NSCLC) patients with histologically confirmed N2 disease are a heterogeneous population, with 5-year survival rates ranging from 10% to 30%. Systemic recurrence following surgery is one of the major problems in stage IIIA(N2) patients, and the use of postoperative chemotherapy (POCT) in stage IIIA disease prolongs survival. The value of postoperative radiotherapy (PORT) for completely resected NSCLC remains controversial, as the effect on survival has been inconclusive. Recently, several large retrospective studies and reviews of the National Cancer Database indicated that modern PORT appears to confer an additional 5% survival advantage beyond that achieved with adjuvant chemotherapy alone. Actually, after complete resection and POCT, 20%-40% of cases have a risk of locoregional recurrence (LRR). Patients with completely resected stage IIIA(N2) disease might hold different postoperative patterns-of-failure and prognosis. It is not yet known for subsets with specific prognostic factors that confer lower LRR risks, whether giving PORT is more effective than no radiation therapy in treating patients with completely resected pathologic stage IIIA(N2) NSCLC.

Purpose: This randomized phase II trial is studying the clinical efficacy of PORT administered using three-dimensional conformal radiotherapy (3D-CRT) techniques and the proposed standard PORT clinical target volume (CTV) delineation guideline in treating low risk of LRR patients with completely resected pathologic stage IIIA(N2) NSCLC.


Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Stage IIIA Radiotherapy Radiation: PORT Drug: Platinum-based two drug chemotherapy (cisplatin/carboplatin + vinorelbine or cisplatin/carboplatin + pemetrexed regimen) Phase 2

Detailed Description:

OBJECTIVES:

  1. Primary

    • Investigate the value of PORT for completely resected pathologic stage IIIa(N2) NSCLC by comparing the disease-free survival of patients with low risk of LRR treated with PORT vs no PORT.
  2. Secondary

    • Determine the overall survival of patients treated with these regimens.
    • Compare the locoregional recurrence-free survival in patients treated with these regimens.
    • Compare the distant metastasis-free survival in patients treated with these regimens.
    • Determine patterns of recurrence in patients treated with these regimens.
    • Determine the treatment-related adverse events of these regimens in these patients.
    • Determine the prediction models for locoregional recurrence and brain metastasis based on the clinical, pathological, radiological, genetic, tumor microenvironmental and immunological data.

OUTLINE: This is a multicenter, randomized study. The clinical risk prediction model for LRR has been established based on our large institutional database. On multivariate analysis, heavy cigarette smoking history, cN2 status, and number of involved lymph nodes>4 were independently significant factors predicting high risk of LRR. The PI equation was built including the three categorical variables and coefficients based on their level of significance: PI=(0.9×smoking history)+(0.5×clinical N status)+(0.8×number of involved lymph nodes). Patients with the PI score<3.5 were considered as low risk of LRR.

Patients are stratified according to participating center, EGFR mutation status (EGFR 19del or 21L858R mutations vs others), and use of pretreatment positron emission tomography scans (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I (PORT): Participants in the Arm I will receive four cycles of adjuvant chemotherapy and after that, sequential adjuvant thoracic conformal radiotherapy (50.4 Gy, 1.8 Gy once daily over 5.5 weeks) will be administered. PORT begins within 2-6 weeks after chemotherapy.

Arm II (no PORT): Participants in the Arm II will receive four cycles of adjuvant chemotherapy and do not undergo adjuvant thoracic conformal radiotherapy.

PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study to Evaluate the Role of Postoperative Radiotherapy for Low Risk of Locoregional Recurrence Patients With Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer
Study Start Date : November 2016
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm I (PORT)
Participants in the Arm I will receive four cycles of adjuvant chemotherapy and after that, sequential adjuvant thoracic conformal radiotherapy (50.4 Gy, 1.8 Gy once daily over 5.5 weeks) will be administered. PORT begins within 2-4 weeks after chemotherapy.
Radiation: PORT
3-dimensional conformal or intensity-modulated radiotherapy, total dose of 50.4 Gy, 1.8 Gy once daily over 5.5 weeks, following the standard and consistent PORT CTV delineation guideline

Drug: Platinum-based two drug chemotherapy (cisplatin/carboplatin + vinorelbine or cisplatin/carboplatin + pemetrexed regimen)
Cisplatin/ carboplatin + vinorelbine regimen for squamous cell lung carcinoma Cisplatin/carboplatin + pemetrexed regimen for lung adenocarcinoma

Placebo Comparator: Arm II (no PORT)
Participants in the Arm II will receive four cycles of adjuvant chemotherapy and after that, do not undergo adjuvant thoracic conformal radiotherapy.
Drug: Platinum-based two drug chemotherapy (cisplatin/carboplatin + vinorelbine or cisplatin/carboplatin + pemetrexed regimen)
Cisplatin/ carboplatin + vinorelbine regimen for squamous cell lung carcinoma Cisplatin/carboplatin + pemetrexed regimen for lung adenocarcinoma




Primary Outcome Measures :
  1. Disease-free survival (DFS) [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 3 years ]
  2. Locoregional recurrence-free survival (LRFS) [ Time Frame: 3 years ]
  3. Distant metastasis-free survival (DMFS) [ Time Frame: 3 years ]
  4. Treatment-related adverse event [ Time Frame: 1 years ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, aged 18 years to 75 years
  • Complete resection through a surgical procedure of lobectomy, sleeve lobectomy or bilobectomy with microscopically tumor-free resection margins and margin-negative resection of all gross disease; Has undergone systematic nodal assessment (lymph node dissection or sampling with a minimum of three N2 stations sampled or completely dissected, one of which must be the subcarinal station)
  • Histologically proven lung adenocarcinoma or squamous cell lung carcinoma of stage pT1-3N2M0 (according to the TNM classification in the Union for International Cancer Control (UICC) 7th ed.)
  • Determined as the postoperative low risk of locoregional recurrence
  • No documented metastases (M1) and/or invasion (T4) by the pretreatment examination or at the time of surgery
  • No prior neoadjuvant therapy (chemotherapy and/or RT)
  • No prior adjuvant thoracic RT
  • No severe perioperative complications and expected postoperative lifespan ≥4 months
  • ECOG Performance Status 0-1
  • Voluntarily participated in this study and signed the informed consent form by himself or his agent. Had good compliance with the study procedures, and can cooperate with the relevant examination, treatment and follow-up

Exclusion Criteria:

  • Histologically confirmed large cell carcinoma, adenosquamous carcinoma, sarcomatoid carcinomas, neuroendocrine tumors (small cell carcinoma, large cell neuroendocrine carcinoma, carcinoid tumors, etc.), salivary-gland type tumors, adenomas, papillomas, or other and unclassified carcinomas
  • Patients undergoing pneumonectomy
  • Diagnosed with other prior or concurrent malignancies (neoplasm) except for basal cell carcinoma of the skin or carcinoma in situ of the cervix within the last 5 years
  • Patients with severe postoperative complications; and time to beginning of the adjuvant therapy has been more than 2 months from the date of surgery
  • Patients with any severe or uncontrolled systematic disease including severe cardiovascular, liver, kidney, hematopoietic, metabolic disease, or uncontrolled active infection that would preclude study participation
  • Patients with positive mental disorder that would preclude study participation;
  • Contradictory to chest radiotherapy
  • Pregnant or nursing women
  • Concurrent other anti-cancer treatment
  • Prior preoperative Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) treatment or other targeted therapy

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): NCT02977169


Contacts
Layout table for location contacts
Contact: Xiaolong Fu, MD 862122200000 ext 3609 xlfu1964@126.com
Contact: Wen Feng, MD 862122200000 ext 3609 fengwen412@126.com

Locations
Layout table for location information
China, Shanghai
Shanghai Chest Hospital Recruiting
Shanghai, Shanghai, China
Contact: Xiaolong Fu, PhD    +862122200000 ext 3602    xlfu1964@126.com   
Sponsors and Collaborators
Shanghai Chest Hospital
Investigators
Layout table for investigator information
Principal Investigator: Xiaolong Fu, MD Shanghai Chest Hospital
Publications:

Layout table for additonal information
Responsible Party: Xiaolong Fu, Director, Department of Radiation Oncology, Shanghai Chest Hospital
ClinicalTrials.gov Identifier: NCT02977169    
Other Study ID Numbers: SCHLC009
First Posted: November 30, 2016    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for 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
Cisplatin
Carboplatin
Pemetrexed
Vinorelbine
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators