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

NCT02977169 | Unknown Phase 2 DMC

• 1 other identifier: SCHLC009
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-small Cell Lung Cancer Stage IIIA; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Disease-free survival (DFS)

  3 years

Secondary Outcomes (4)

• Overall survival (OS)

  3 years

• Locoregional recurrence-free survival (LRFS)

  3 years

• Distant metastasis-free survival (DMFS)

  3 years

• Treatment-related adverse event

  1 years

Study Arms (2)

Arm I (PORT)

EXPERIMENTAL

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; Drug: Platinum-based two drug chemotherapy (cisplatin/carboplatin + vinorelbine or cisplatin/carboplatin + pemetrexed regimen)

Arm II (no PORT)

PLACEBO COMPARATOR

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)

Interventions

PORT RADIATION

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

Arm I (PORT)

Platinum-based two drug chemotherapy (cisplatin/carboplatin + vinorelbine or cisplatin/carboplatin + pemetrexed regimen) DRUG

Cisplatin/ carboplatin + vinorelbine regimen for squamous cell lung carcinoma Cisplatin/carboplatin + pemetrexed regimen for lung adenocarcinoma

Arm I (PORT); Arm II (no PORT)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

RECRUITING

Related Publications (7)

• 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.

  PMID: 20338627 BACKGROUND

• Lally BE, Zelterman D, Colasanto JM, Haffty BG, Detterbeck FC, Wilson LD. Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database. J Clin Oncol. 2006 Jul 1;24(19):2998-3006. doi: 10.1200/JCO.2005.04.6110. Epub 2006 Jun 12.

  PMID: 16769986 BACKGROUND

• 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.

  PMID: 18439766 BACKGROUND

• 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.

  PMID: 25667283 BACKGROUND

• 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.

  PMID: 24100149 BACKGROUND

• 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.

  PMID: 27727451 BACKGROUND

• 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.

  PMID: 24529715 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cisplatin; Carboplatin; Vinorelbine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Xiaolong Fu, MD

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaolong Fu, MD

CONTACT

862122200000; xlfu1964@126.com

Wen Feng, MD

CONTACT

862122200000; fengwen412@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Department of Radiation Oncology

Study Record Dates

• First Submitted: November 27, 2016
• First Posted: November 30, 2016
• Study Start: November 1, 2016
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: November 13, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)