Radiotherapy Plus Anlotinib in LA-NSCLC Intolerable to cCRT

Official title

Efficiency and Safety of Radiotherapy Combined With Anlotinib in Locally Advanced Non-small Cell Lung Cancer Patients Intolerable to Concurrent Chemoradiotherapy: A Phase II Single-arm Trial

Overview

Concurrent chemoradiotherapy (cCRT) is the standard treatment for patients with negative epidermal growth factor receptor (EGFR)-mutated unresectable locally advanced non-small cell lung cancer (LA-NSCLC). However, parts of patients only receive sequential chemoradiotherapy (sCRT) due to various reasons. This phase II study aimed to improve the outcomes of patients receiving sCRT by combining anti-angiogenesis therapy (Anlotinib) during radiotherapy course.We hypothesize that the combination of radiotherapy with anlotinib could improve the 2-year PFS rate from 35% with sCRT to 50. The accrual target was 44 patients.

Interventions

• Drug Anlotinib
  For patients treated with conventional Intensity-Modulated Radiation Therapy (IMRT), the median prescribed dose was 60 Gy/30 fractions (range: 50.0-70.0 Gy, in 25-35 fractions) (median BED10 72 Gy, range: 60-84 Gy) to the planning target volume (PTV). As for patients with IMRT-based simultaneously integrated boost (SIB), the median prescribed dose was 59.92 Gy/28 fractions (range: 50.0-70.0 Gy, in 25-33 fractions) (median BED10 72.74 Gy, range: 60-84 Gy) to the planning gross tumor volume (PGTV)

Primary outcome measures

• 2-year progression-free survival (PFS) [Time frame: From the first day of radiotherapy to the occurrence of objective tumor progression or death due to any cause, whichever occurs first, assessed up to 60 months]

Secondary outcome measures (4)

• Overall Survival(OS) [Time frame: From the first day of radiotherapy to the occurrence of death due to any cause, assessed up to 60 months]
• Local regional recurrence (LR) [Time frame: From the first day of radiotherapy to the occurrence of clinical and/or biopsy-proven recurrence within the bronchial stump, ipsilateral hilum, mediastinum, or supraclavicular, whichever occurs first, assessed up to 60 months]
• Distant metastasis (DM) [Time frame: From the first day of radiotherapy to the occurrence of any evidence of metastatic disease beyond the locoregional regions previously mentioned, assessed up to 60 months]
• Acute toxicity [Time frame: From the first day of radiotherapy and up to the 3-month post-radiotherapy follow-up visit]

Eligibility criteria

Patients with histologically or cytologically confirmed negative EGFR (including EGFR exon 19 deletion or L858R mutations) or ALK/ROS1-mutated locally advanced unresectable NSCLC were screened.

Inclusion criteria

• ≥18 years old with no restrictions on sex;
• Peripheral tumor, or central lung cancer with non-squamous tissue or a mixed tissue with less than 50% squamous carcinoma;
• Eastern cooperative oncology group (ECOG) score ≤2 was required;
• Received systemic chemotherapy or combined chemotherapy and immumitherapy for ≥ 4 weeks without progression;
• .No cavity inside the tumor, and located ≥ 1 cm of the main pulmonary artery trunk;
• No symptoms of hemoptysis;
• Adequate hepatic and renal functions with a negative urine protein;
• Expected survival of more than 6 months.

Exclusion criteria

• currently receiving treatment for malignancies at other sites, except for curable non-melanoma skin cancer and cervical carcinoma in situ;
• previous malignancy within five years;
• thoracic radiotherapy history, hemoptysis, myocardial infarction or cerebrovascular accident within three months;
• uncontrolled or active pulmonary inflammation;
• participated in other clinical trials;
• Pregnant women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Department of Radiation Oncology,Cancer Institute and Hospital,Chinese — Beijing

Publications

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• Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Faivre-Finn C, Reck M, Vansteenkiste J, Spigel DR, Wadsworth C, Melillo G, Taboada M, Dennis PA, Ozguroglu M; PACIFIC Investigators. Ove PMID 30280658
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• Garassino MC, Mazieres J, Reck M, Chouaid C, Bischoff H, Reinmuth N, Cove-Smith L, Mansy T, Cortinovis D, Migliorino MR, Delmonte A, Sanchez JG, Chara Velarde LE, Bernabe R, Paz-Ares L, Perez ID, Trunova N, Foroutanpour K, Faivre-Finn C. Durvalumab After Sequential Chemoradiotherapy in Stage III, Unresectable NSCLC: The Phase 2 PACIFIC-6 Trial. J Thorac Oncol. 2022 Dec;17(12):1415-1427. doi: 10.10 PMID 35961520
• Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1341-6. doi: 10.1016/0360-3016(95)00060-C. No abstract available. PMID 7713792
• Han B, Li K, Wang Q, Zhang L, Shi J, Wang Z, Cheng Y, He J, Shi Y, Zhao Y, Yu H, Zhao Y, Chen W, Luo Y, Wu L, Wang X, Pirker R, Nan K, Jin F, Dong J, Li B, Sun Y. Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non-Small Cell Lung Cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2018 Nov 1;4(11):1569-1575. doi: 10.1001/jam PMID 30098152
• Wang D, Bi N, Zhang T, Zhou Z, Xiao Z, Liang J, Chen D, Hui Z, Lv J, Wang X, Wang X, Deng L, Wang W, Wang J, Wang C, Lu X, Xu K, Wu L, Xue W, Feng Q, Wang L. Comparison of efficacy and safety between simultaneous integrated boost intensity-modulated radiotherapy and conventional intensity-modulated radiotherapy in locally advanced non-small-cell lung cancer: a retrospective study. Radiat Oncol. 20 PMID 31196118

Identifiers

NCT: NCT07037680 · NCC2827

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗