Sintilimab Combined With Anlotinib Therapy for Initially Unresectable Non-small Cell Lung Cancer
23 mars 2022 mis à jour par: 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.
Aperçu de l'étude
Statut
Pas encore de recrutement
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Interventionnel
Inscription (Anticipé)
93
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Coordonnées de l'étude
- Nom: Yingyi Wang, Professor
- Numéro de téléphone: +86 010-69158764
- E-mail: wangyingyi@pumch.cn
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 75 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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.
Autres noms:
Anlotinib will be given at a dose of 12mg once daily on days 1-14 of a 21-day cycle.
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Surgical conversion rate
Délai: 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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Objective response rate (ORR)
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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
Délai: 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
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Chercheur principal: Chunmei Bai, Professor, Peking union medical colloge hospital
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- Faivre-Finn C, Vicente D, Kurata T, Planchard D, Paz-Ares L, Vansteenkiste JF, Spigel DR, Garassino MC, Reck M, Senan S, Naidoo J, Rimner A, Wu YL, Gray JE, Ozguroglu M, Lee KH, Cho BC, Kato T, de Wit M, Newton M, Wang L, Thiyagarajah P, Antonia SJ. Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC-an Update From the PACIFIC Trial. J Thorac Oncol. 2021 May;16(5):860-867. doi: 10.1016/j.jtho.2020.12.015. Epub 2021 Jan 19.
- 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.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Anticipé)
1 avril 2022
Achèvement primaire (Anticipé)
1 avril 2024
Achèvement de l'étude (Anticipé)
1 avril 2026
Dates d'inscription aux études
Première soumission
21 mars 2022
Première soumission répondant aux critères de contrôle qualité
23 mars 2022
Première publication (Réel)
1 avril 2022
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
1 avril 2022
Dernière mise à jour soumise répondant aux critères de contrôle qualité
23 mars 2022
Dernière vérification
1 mars 2022
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- HS-3340
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
OUI
Description du régime IPD
De-identified individual participant data for all primary and secondary outcome measures will be made available.
Délai de partage IPD
Data will be available within 1 year of study completion
Critères d'accès au partage IPD
Data access requests will be reviewed by an external independent Review Panel.
Requestors will be required to sign a Data Access Agreement
Type d'informations de prise en charge du partage d'IPD
- PROTOCOLE D'ÉTUDE
- SÈVE
- CIF
- ANALYTIC_CODE
- RSE
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Non
Étudie un produit d'appareil réglementé par la FDA américaine
Non
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .