Sintilimab Combined With Anlotinib Therapy for Initially Unresectable Non-small Cell Lung Cancer
2022年3月23日 更新者：YueJuan Cheng、Peking Union Medical College Hospital
Sintilimab Combined With Anlotinib Therapy for Patients With Initially Unresectable Stage II-III Non-small Cell Lung Cancer: A Prospective, Single-arm Study
Concurrent or sequential chemoradiotherapy has been recommended as the standard treatment for locally advanced and unresectable non-small cell lung cancer (NSCLC).
However, its efficacy remains to be improved.
PD-1/PD-L1 inhibitors have been proven to be effective for late-stage NSCLC, and anti-angiogenesis agents have also been used for the first-line treatment of advanced or metastatic NSCLC.
Therefore, we designed this single-arm clinical trial, which aims to investigate the safety and feasibility of sintilimab combined with anlotinib therapy for patients with initially unresectable stage II-III NSCLC.
調査の概要
詳細な説明
Concurrent or sequential chemoradiotherapy is the standard treatment for patients with locally advanced NSCLC, but patients receiving chemoradiotherapy have limited improvement in prognosis and are almost impossible to achieve a radical cure.
Considering the excellent effect of immunotherapy and anti-angiogenesis therapy in NSCLC, we designed this single-arm clinical study, which aims to investigate the safety and feasibility of sintilimab combined with anlotinib therapy for patients with initially unresectable stage II-III NSCLC, in order to enable patients to achieve further surgical treatment and prolonged survival.
研究の種類
介入
入学 (予想される)
93
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Yingyi Wang, Professor
- 電話番号：+86 010-69158764
- メール：wangyingyi@pumch.cn
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～75年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients with locally advanced (stage II-III C) NSCLC confirmed by histology who are initially unable to undergo surgery and concomitant radiochemotherapy and are confirmed to have at least one measurable lesion according to RECIST 1.1.
- Age ≥18 years and ≤75 years.
- ECOG PS score: 0 to 1.
The main organs function is normal, that is, the following criteria met:
- Good hematopoietic function, defined as absolute neutrophil count ≥1.5×109 /L, platelet count≥100 ×109 /L, hemoglobin ≥90g/L [no blood transfusion or no erythropoietin (EPO) dependence within 7 days before enrollment];
- Biochemical test results should meet the following criteria: BIL < 1.25 times the upper limit of normal value (ULN); ALT and AST < 2.5 × ULN; in case of liver metastases, ALT and AST < 5 × ULN; Cr ≤1.5×ULN or creatinine clearance (CCr) ≥60ml/min; Coagulation function is good, INR and PT ≤1.5 × ULN;
- The oxygen saturation of the finger tip ≥ 92% both at rest and during walking (without oxygen inhalation).
- The life expectancy ≥12 weeks.
- Signed and dated informed consent.
Exclusion Criteria:
- Subjects at risk of massive hemoptysis or with blood in sputum, including but not limited to tumor lesions no more than 5 mm away from large vessels, tumors invading large vessels, and obvious lung cavity/necrotizing tumors.
- Small cell lung cancer (including mixed small cell and non-small cell lung cancer) or central squamous cell carcinoma.
- With driver mutation (EGFR/ALK/ROS1).
- With uncontrollable hypertension (systolic pressure > 160 mmHg, diastolic pressure > 100 mmHg) even receiving antihypertensive drug therapy.
- Has an active autoimmune disease, history of allogeneic stem cell transplantation or organ transplantation that has required systemic treatment. Replacement therapy is not considered a form of systemic treatment and is allowed.
- Has an active infection requiring systemic therapy.
- Has other malignant tumors (except radical cervical carcinoma in situ, non-melanoma skin cancer, etc.) or concomitant diseases that seriously endanger the patients or affect the patients completing the study at the same time.
- With immunodeficiency status, including but not limited to HIV infection and primary immunodeficiency diseases.
- Previously treated with ICIs.
- Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Experimental arm
Sintilimab will be given intravenously at a dose of 200mg every 21 days. Anlotinib will be given at a dose of 12mg once daily on days 1-14 of a 21-day cycle. Tumor evaluation will be conducted after treatment of the tested regimen every 2 cycles. Subsequent treatment will be determined based on the evaluation results: If the patients are not suitable for radical surgery, but the result of efficacy evaluation is CR, PR, or SD, they can continue to receive the tested regimen. If the patients are still not suitable for radical surgery after 6 cycles of the tested regimen, the standard first-line or immunotherapy after chemoradiotherapy or radiotherapy will be given. If patients are eligible for radical surgery, surgery will be performed within 4 weeks after completion of the last tested regimen. |
Sintilimab will be given intravenously at a dose of 200mg every 21 days.
他の名前：
Anlotinib will be given at a dose of 12mg once daily on days 1-14 of a 21-day cycle.
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Surgical conversion rate
時間枠：18 weeks from the initiation of the tested regime therapy
|
The surgical conversion rate was defined as the proportion of subjects with the successful conversion over all subjects who received the tested regime.
|
18 weeks from the initiation of the tested regime therapy
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Objective response rate (ORR)
時間枠：18 weeks from the initiation of the tested regime therapy
|
ORR is defined as the percentage of participants who have the best overall response (BOR) of complete response (CR) or partial response (PR) assessed based on RECIST 1.1.
|
18 weeks from the initiation of the tested regime therapy
|
|
R0 resection rate
時間枠：within 28 working days after operation
|
R0 resection rate is defined as the complete resection rate of all tumor under microscope.
|
within 28 working days after operation
|
|
Major pathological response rate
時間枠：within 28 working days after operation
|
Major pathological response rate is defined as the percentage of patients who achieved a major pathological response (residual tumor ≤10%).
|
within 28 working days after operation
|
|
Pathological complete response rate
時間枠：within 28 working days after operation
|
Pathological complete response rate is defined as the percentage of patients who achieved a pathological complete response (residual tumor = 0%).
|
within 28 working days after operation
|
|
Overall survival (OS)
時間枠：2 years from the initiation of the tested regime therapy
|
OS is measured from the time from the treatment onset (date of first study dose) until the date of death from any cause.
|
2 years from the initiation of the tested regime therapy
|
|
Progression-free survival (PFS)
時間枠：2 years from the initiation of the tested regime therapy
|
PFS is measured from the time from the treatment onset (date of first study dose) until the date of tumor progression or death from any cause.
|
2 years from the initiation of the tested regime therapy
|
|
Disease-free survival (DFS)
時間枠：2 years from the initiation of the tested regime therapy
|
DFS is measured from the time from radical surgery until the date of tumor progression or death from any cause.
|
2 years from the initiation of the tested regime therapy
|
|
Treatment-related adverse events
時間枠：3 months from the end of the tested regime therapy
|
Incidence and grade of treatment-related adverse events assessed based on CTCAE 5.0
|
3 months from the end of the tested regime therapy
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Chunmei Bai, Professor、Peking union medical colloge hospital
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
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- De Ruysscher D, Botterweck A, Dirx M, Pijls-Johannesma M, Wanders R, Hochstenbag M, Dingemans AM, Bootsma G, Geraedts W, Simons J, Pitz C, Lambin P. Eligibility for concurrent chemotherapy and radiotherapy of locally advanced lung cancer patients: a prospective, population-based study. Ann Oncol. 2009 Jan;20(1):98-102. doi: 10.1093/annonc/mdn559. Epub 2008 Aug 20.
- Mery B, Guy JB, Swalduz A, Vallard A, Guibert C, Almokhles H, Ben Mrad M, Rivoirard R, Falk AT, Fournel P, Magne N. The evolving locally-advanced non-small cell lung cancer landscape: Building on past evidence and experience. Crit Rev Oncol Hematol. 2015 Nov;96(2):319-27. doi: 10.1016/j.critrevonc.2015.05.020. Epub 2015 Jun 7.
- Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick S, Brahmer J, Swanson SJ et al: Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as neoadjuvant treatment (tx) for resectable (IB-IIIA) non-small cell lung cancer (NSCLC) in the phase 3 CheckMate 816 trial. Cancer research 2021, 81(13 SUPPL).
- Xiao W, Hong M. Concurrent vs sequential chemoradiotherapy for patients with advanced non-small-cell lung cancer: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2021 Mar 19;100(11):e21455. doi: 10.1097/MD.0000000000021455.
- Eberhardt WE, Pottgen C, Gauler TC, Friedel G, Veit S, Heinrich V, Welter S, Budach W, Spengler W, Kimmich M, Fischer B, Schmidberger H, De Ruysscher D, Belka C, Cordes S, Hepp R, Lutke-Brintrup D, Lehmann N, Schuler M, Jockel KH, Stamatis G, Stuschke M. Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA(N2) and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy (ESPATUE). J Clin Oncol. 2015 Dec 10;33(35):4194-201. doi: 10.1200/JCO.2015.62.6812. Epub 2015 Nov 2.
- Deng H, Liu J, Cai X, Chen J, Rocco G, Petersen RH, Brunelli A, Ng CSH, D'Amico TA, Liang W, He J. Radical Minimally Invasive Surgery After Immuno-chemotherapy in Initially-unresectable Stage IIIB Non-small cell Lung Cancer. Ann Surg. 2022 Mar 1;275(3):e600-e602. doi: 10.1097/SLA.0000000000005233.
- Chu T, Zhong R, Zhong H, Zhang B, Zhang W, Shi C, Qian J, Zhang Y, Chang Q, Zhang X, Dong Y, Teng J, Gao Z, Qiang H, Nie W, Zhao Y, Han Y, Chen Y, Han B. Phase 1b Study of Sintilimab Plus Anlotinib as First-line Therapy in Patients With Advanced NSCLC. J Thorac Oncol. 2021 Apr;16(4):643-652. doi: 10.1016/j.jtho.2020.11.026. Epub 2021 Jan 29.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (予想される)
2022年4月1日
一次修了 (予想される)
2024年4月1日
研究の完了 (予想される)
2026年4月1日
試験登録日
最初に提出
2022年3月21日
QC基準を満たした最初の提出物
2022年3月23日
最初の投稿 (実際)
2022年4月1日
学習記録の更新
投稿された最後の更新 (実際)
2022年4月1日
QC基準を満たした最後の更新が送信されました
2022年3月23日
最終確認日
2022年3月1日
詳しくは
本研究に関する用語
その他の研究ID番号
- HS-3340
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
De-identified individual participant data for all primary and secondary outcome measures will be made available.
IPD 共有時間枠
Data will be available within 1 year of study completion
IPD 共有アクセス基準
Data access requests will be reviewed by an external independent Review Panel.
Requestors will be required to sign a Data Access Agreement
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
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米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
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