Evaluating Efficacy and Safety of Anlotinib Combined With Concurrent Chemoradiotherapy Followed by Consolidation Immunotherapy for Locally Advanced Non-small Cell Lung Cancer

Efficacy and Safety Clinical Trial

Official title:

Evaluating Anlotinib Combined With Concurrent Chemoradiotherapy Followed by Consolidation Immunotherapy Versus Concurrent Chemoradiotherapy Followed by Consolidation Immunotherapy for Locally Advanced Non-small Cell Lung Cancer: A Prospective, Randomized Controlled Phase II Clinical Trial

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05481775
• Other study ID #: GASTO-1088
• Status: Withdrawn
• Phase: Phase 2
• Start date: April 1, 2022
• Est. completion date: September 30, 2025

Study information

• Verified date: November 2022
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, randomized, controlled phase II clinical study for evaluating anlotinib combined with concurrent chemoradiotherapy followed by consolidation immunotherapy versus concurrent chemoradiotherapy followed by consolidation immunotherapy in locally advanced, unresectable NSCLC.

Description:

This is a prospective, randomized, controlled phase II clinical study for evaluating anlotinib combined with concurrent chemoradiotherapy followed by consolidation immunotherapy versus concurrent chemoradiotherapy followed by consolidation immunotherapy in locally advanced, unresectable NSCLC. In this study, the enrolled patients were divided into the experimental group and the control group at a ratio of 1:1. The patients in the experimental group received anlotinib combined with curative concurrent chemoradiotherapy first, while the patients in the control group received curative concurrent chemoradiotherapy. Those who are evaluated as CR, PR or SD after the aforementioned treatment will enter consolidation immunotherapy. Patients will receive tislelizumab 200mg iv. drip, Q3W, for up to 12 months.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 30, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• informed consent is required before proceeding with any steps in the study;

• Male or female 18-75 years old;

• Patients must be locally advanced, unresectable (stage IIIA-IIIC) with histology reported NSCLC (except for central squamous cell carcinoma or those at risk for massive hemoptysis);

• No prior chemotherapy, immunotherapy, radiotherapy, surgery, or targeted therapy;

• Tumor sample requirements: must provide sufficient evidence to allow analysis Stained, archived tumor tissue samples;

• Life expectancy = 12 weeks;

• World Health Organization (WHO) PS score of 0 or 1;

• Postmenopausal women, or negative urine or serum pregnancy test (HCG) within 14 days prior to study drug administration

• Women of childbearing potential (WOCBP) must agree to adhere to contraceptive methods during study drug treatment and for 6 months after the last study drug treatment;

• Men who have sex with WOCBP must agree to adhere to contraception during study drug treatment and for 6 months after the last study drug treatment;

• azoospermic men do not have to adhere to contraceptive requirements. Adolescents of childbearing potential without heterosexual sex (WOCBP) do not have to comply with contraceptive requirements, but must still undergo a pregnancy test as described in this section;

• Organ and bone marrow function meet the following conditions: Forced expiratory volume in 1 second (FEV1) = 800ml; Absolute neutrophil count =1.5×10^9/L; Platelet =100×10^9/L; Hemoglobin =9.0g/dL; Serum creatinine clearance calculated according to Cockcroft-Gault formula =50 mL/ min (Cockcroft and Gault 1976); Serum bilirubin = 1.5 times the upper limit of normal (ULN); AST and ALT = 2.5 times ULN.

Exclusion Criteria:

• Concurrent participation in another clinical study, unless it is an observational (non-interventional) clinical study;

• Histological type of small cell lung cancer (including mixed small cell and non-small cell lung cancer);

• Prior use of any targeted therapy;

• The central cavity squamous cell carcinoma or non-small cell lung cancer with hemoptysis (the amount of hemoptysis> 50 ml/d);

• The patient has conditions that affect oral medication (such as dysphagia, chronic diarrhea, intestinal obstruction, etc.) ;

• Major surgery (excluding vascular access) within 4 weeks prior to study entry;

• Heart rate-corrected mean QT interval (QTc) = 470 ms, calculated from 3 electrocardiogram calculation cycles (ECG) using Bazett correction;

• No Controlled complications, including but not limited to persistent or active infection, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmia, active peptic ulcer disease or gastritis, active hemorrhagic Illness, including any known HBsAg-positive patient with HBV DNA > 500 IU/ml, Hepatitis C or Human Immunodeficiency Virus (HIV), or mental illness that would limit compliance with study requirements or impair the patient's ability to give written informed consent/ Social status;

• History of another primary malignancy within 5 years prior to initiation of therapy, excluding adequately treated skin basal or squamous cell carcinoma or cervical carcinoma in situ;

• Pregnant, breastfeeding women; Contraceptive method, male or female of reproductive potential; - Conditions that may interfere with the evaluation of the efficacy or safety of the treatment.

• Patients who progressed after concurrent chemoradiotherapy;

• History of tuberculosis, excluding old pulmonary tuberculosis;

• Received live attenuated vaccine within 30 days before study initiation or within 30 days after tislelizide;

• In Use of immunosuppressive drugs within 28 days prior to the first dose of tislelizumab. Of these, intranasal inhaled corticosteroids at physiological doses are excluded; prednisone or an equivalent amount of systemic corticosteroids not exceeding 10 mg per day is excluded. Steroids are permitted for management of chemoradiotherapy-related toxicity;

• Patients with unrecovered CTCAE > 2 toxicity after prior targeted combination chemoradiotherapy will be excluded from randomization;

• due to prior targeted combined chemoradiotherapy, patients with grade =2 pneumonitis undergoing chemotherapy will be excluded from randomization.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Efficacy and Safety
• Locally Advanced Non-small Cell Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• Anlotinib
Anlotinib 8mg qd po. Taking anlotinib daily for 2 weeks and stop for 1 week.
• Chemotherapy
Docetaxel 25mg/m2 + Cisplatin 25mg/m2 QW

Radiation:
• Radiotherapy
Thoracic radiotherapy was delivered using the daily image-guided intensity modulated radiation therapy (IMRT) technique. The total radiation dose was 66-68 Gy to the gross tumor in 17-22 daily fractions.

Drug:
• Immunotherapy
consolidation Immunotherapy (Tislelizhu 200mg iv. drip, Q3W, up to 12 months.)

Locations

Country	Name	City	State
China	Sun yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (14)

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Guo L, Zhang L, Guan Y, Li Y, Zhang C, Guo Q. In vitro studies of H520 cell cycle and apoptosis by anlotinib combined with radiotherapy. Thorac Cancer. 2021 Mar;12(5):593-602. doi: 10.1111/1759-7714.13780. Epub 2021 Jan 12. — View Citation

He Z, Liu J, Ma Y, Jiang H, Cui Z, Wang G, Wu Y, Liu J, Cai X, Qian J, Huang J, Zhang H, Li H. Anlotinib Combined with Cranial Radiotherapy for Non-Small Cell Lung Cancer Patients with Brain Metastasis: A Retrospectively, Control Study. Cancer Manag Res. — View Citation

Liao ZX, Komaki RR, Thames HD Jr, Liu HH, Tucker SL, Mohan R, Martel MK, Wei X, Yang K, Kim ES, Blumenschein G, Hong WK, Cox JD. Influence of technologic advances on outcomes in patients with unresectable, locally advanced non-small-cell lung cancer recei — View Citation

Lin B, Song X, Yang D, Bai D, Yao Y, Lu N. Anlotinib inhibits angiogenesis via suppressing the activation of VEGFR2, PDGFRbeta and FGFR1. Gene. 2018 May 15;654:77-86. doi: 10.1016/j.gene.2018.02.026. Epub 2018 Feb 14. Erratum In: Gene. 2020 Jan 10;723:144 — View Citation

Liu S, Qin T, Liu Z, Wang J, Jia Y, Feng Y, Gao Y, Li K. anlotinib alters tumor immune microenvironment by downregulating PD-L1 expression on vascular endothelial cells. Cell Death Dis. 2020 May 4;11(5):309. doi: 10.1038/s41419-020-2511-3. — View Citation

Palakurthi S, Kuraguchi M, Zacharek SJ, Zudaire E, Huang W, Bonal DM, Liu J, Dhaneshwar A, DePeaux K, Gowaski MR, Bailey D, Regan SN, Ivanova E, Ferrante C, English JM, Khosla A, Beck AH, Rytlewski JA, Sanders C, Laquerre S, Bittinger MA, Kirschmeier PT, — View Citation

Wang Y, Deng W, Li N, Neri S, Sharma A, Jiang W, Lin SH. Combining Immunotherapy and Radiotherapy for Cancer Treatment: Current Challenges and Future Directions. Front Pharmacol. 2018 Mar 5;9:185. doi: 10.3389/fphar.2018.00185. eCollection 2018. Review. — View Citation

Wu B, McNutt T, Zahurak M, Simari P, Pang D, Taylor R, Sanguineti G. Fully automated simultaneous integrated boosted-intensity modulated radiation therapy treatment planning is feasible for head-and-neck cancer: a prospective clinical study. Int J Radiat — View Citation

Yang Y, Li L, Jiang Z, Wang B, Pan Z. Anlotinib optimizes anti-tumor innate immunity to potentiate the therapeutic effect of PD-1 blockade in lung cancer. Cancer Immunol Immunother. 2020 Dec;69(12):2523-2532. doi: 10.1007/s00262-020-02641-5. Epub 2020 Jun — View Citation

Zhuang H, Wang Y, Cheng C, Shi S. The efficacy of anlotinib instead of glucocorticoids for edema induced by brain metastases in NSCLC patients with anti-PD1/PDL-1 immunotherapy. Neuro Oncol. 2021 Jan 30;23(1):169-171. doi: 10.1093/neuonc/noaa236. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	18-months progression-free survival rate	From the first day of treatment to the day of progression or the day of death.	18-months
Secondary	Overall survival	It was calculated from the first day of treatment to the day of death.	18-months
Secondary	objective response rate	The proportion patients evaluated for CR and PR	18-months
Secondary	Incidence of Treatment-related Adverse Events	Adverse effects are graded according to the CTCAE 5.0 version, including multiple organs and tissues, such as gastrointestinal disease and symptom, cardiovascular disease, respiratory diseases and so on.	18 months after therapy
Secondary	Score of EORTC QLQ-C30	The evaluation of life quality	18 months after therapy