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

Primary Purpose

Non-small Cell Lung Cancer Stage IIIA, Radiotherapy

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
PORT
Platinum-based two drug chemotherapy (cisplatin/carboplatin + vinorelbine or cisplatin/carboplatin + pemetrexed regimen)
Sponsored by
Shanghai Chest Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer Stage IIIA

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Shanghai Chest HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (PORT)

Arm II (no PORT)

Arm Description

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.

Participants in the Arm II will receive four cycles of adjuvant chemotherapy and after that, do not undergo adjuvant thoracic conformal radiotherapy.

Outcomes

Primary Outcome Measures

Disease-free survival (DFS)

Secondary Outcome Measures

Overall survival (OS)
Locoregional recurrence-free survival (LRFS)
Distant metastasis-free survival (DMFS)
Treatment-related adverse event
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Full Information

First Posted
November 27, 2016
Last Updated
November 12, 2020
Sponsor
Shanghai Chest Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02977169
Brief Title
To Evaluate the Role of Postoperative Radiotherapy in Patients With IIIA(N2) Non-Small Cell Lung Cancer
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 Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 2016 (undefined)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Chest Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
OBJECTIVES: 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer Stage IIIA, Radiotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I (PORT)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm II (no PORT)
Arm Type
Placebo Comparator
Arm Description
Participants in the Arm II will receive four cycles of adjuvant chemotherapy and after that, do not undergo adjuvant thoracic conformal radiotherapy.
Intervention Type
Radiation
Intervention Name(s)
PORT
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Platinum-based two drug chemotherapy (cisplatin/carboplatin + vinorelbine or cisplatin/carboplatin + pemetrexed regimen)
Intervention Description
Cisplatin/ carboplatin + vinorelbine regimen for squamous cell lung carcinoma Cisplatin/carboplatin + pemetrexed regimen for lung adenocarcinoma
Primary Outcome Measure Information:
Title
Disease-free survival (DFS)
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Time Frame
3 years
Title
Locoregional recurrence-free survival (LRFS)
Time Frame
3 years
Title
Distant metastasis-free survival (DMFS)
Time Frame
3 years
Title
Treatment-related adverse event
Description
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame
1 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaolong Fu, MD
Phone
862122200000
Ext
3609
Email
xlfu1964@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Wen Feng, MD
Phone
862122200000
Ext
3609
Email
fengwen412@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaolong Fu, MD
Organizational Affiliation
Shanghai Chest Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Chest Hospital
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaolong Fu, PhD
Phone
+862122200000
Ext
3602
Email
xlfu1964@126.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
20338627
Citation
NSCLC Meta-analyses Collaborative Group; Arriagada R, Auperin A, Burdett S, Higgins JP, Johnson DH, Le Chevalier T, Le Pechoux C, Parmar MK, Pignon JP, Souhami RL, Stephens RJ, Stewart LA, Tierney JF, Tribodet H, van Meerbeeck J. Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet. 2010 Apr 10;375(9722):1267-77. doi: 10.1016/S0140-6736(10)60059-1. Epub 2010 Mar 24.
Results Reference
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16769986
Citation
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Results Reference
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18439766
Citation
Douillard JY, Rosell R, De Lena M, Riggi M, Hurteloup P, Mahe MA; Adjuvant Navelbine International Trialist Association. Impact of postoperative radiation therapy on survival in patients with complete resection and stage I, II, or IIIA non-small-cell lung cancer treated with adjuvant chemotherapy: the adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial. Int J Radiat Oncol Biol Phys. 2008 Nov 1;72(3):695-701. doi: 10.1016/j.ijrobp.2008.01.044. Epub 2008 Apr 24.
Results Reference
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PubMed Identifier
25667283
Citation
Robinson CG, Patel AP, Bradley JD, DeWees T, Waqar SN, Morgensztern D, Baggstrom MQ, Govindan R, Bell JM, Guthrie TJ, Colditz GA, Crabtree TD, Kreisel D, Krupnick AS, Patterson GA, Meyers BF, Puri V. Postoperative radiotherapy for pathologic N2 non-small-cell lung cancer treated with adjuvant chemotherapy: a review of the National Cancer Data Base. J Clin Oncol. 2015 Mar 10;33(8):870-6. doi: 10.1200/JCO.2014.58.5380. Epub 2015 Feb 9.
Results Reference
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PubMed Identifier
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Citation
Billiet C, Decaluwe H, Peeters S, Vansteenkiste J, Dooms C, Haustermans K, De Leyn P, De Ruysscher D. Modern post-operative radiotherapy for stage III non-small cell lung cancer may improve local control and survival: a meta-analysis. Radiother Oncol. 2014 Jan;110(1):3-8. doi: 10.1016/j.radonc.2013.08.011. Epub 2013 Oct 4. Erratum In: Radiother Oncol. 2014 Nov;113(2):300-1.
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Citation
Burdett S, Rydzewska L, Tierney J, Fisher D, Parmar MK, Arriagada R, Pignon JP, Le Pechoux C; PORT Meta-analysis Trialists Group. Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev. 2016 Oct 11;10(10):CD002142. doi: 10.1002/14651858.CD002142.pub4.
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Citation
Feng W, Fu XL, Cai XW, Yang HJ, Wu KL, Fan M, Xiang JQ, Zhang YW, Chen HQ. Patterns of local-regional failure in completely resected stage IIIA(N2) non-small cell lung cancer cases: implications for postoperative radiation therapy clinical target volume design. Int J Radiat Oncol Biol Phys. 2014 Apr 1;88(5):1100-7. doi: 10.1016/j.ijrobp.2013.12.048. Epub 2014 Feb 11.
Results Reference
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To Evaluate the Role of Postoperative Radiotherapy in Patients With IIIA(N2) Non-Small Cell Lung Cancer

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