The Impact of Thymosin α-1 on the Efficacy of Concurrent Chemoradiotherapy Followed by Immunotherpay Consolidation for Locally Advanced NSCLC

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Prospective Phase II Controlled Study to Evaluate the Impact of Thymosin Alpha 1 on the Completion Rate of Consolidation Immunotherapy After Radical Radiochemotherapy for Locally Advanced Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06139419
• Other study ID #: GASTO-1098
• Status: Recruiting
• Phase: Phase 2
• Start date: July 25, 2023
• Est. completion date: August 2026

Study information

• Verified date: November 2023
• Source: Sun Yat-sen University
• Contact: Bo Qiu, Professor
• Phone: +86-020-87343031
• Email: qiubo[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This prospective phase II randomized study is to determine the impact of thymosin alpha-1 on the concurrent chemoradiotherpay followed by immunotherapy consolidation in patients with locally advanced NSCLC by assessing the survival outcomes, treatment responses and toxicities.

Description:

This prospective phase II randomized study is to determine the impact of thymosin alpha-1 on the concurrent chemoradiotherpay followed by immunotherapy consolidation in patients with locally advanced NSCLC by assessing the survival outcomes, treatment responses and toxicities.

Patients with locally advanced NSCLC who will receive concurrent radiochemotherapy followed by immunotherapy consolidation will be randomly divided into two groups (concurrent Tα1 treatment group and control group [in which Tα1 will not be used]), and the overall survivals, progression-free survivals (PFS), completion rate of immunotherapy consolidation, toxicities/adverse effects, and peripheral blood immune biomarkers will be compared between these two groups.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. completion date: August 2026
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• aged =18 years old

• histologically confirmed locally advanced and unresectable NSCLC;

• no prior radiotherapy or surgery;

• with the life expectancy over 12 weeks;

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

• adequate bone marrow and hepatic and renal functions;

• informed consent

Exclusion Criteria:

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

• With histologically documented combined small-cell lung carcinoma;

• Major surgery (excluding vascular access placement) within 4 weeks prior to enrollment in the study;

• Active or prior documented autoimmune disease within the past 2 years;

• Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis);

• History of innate immunodeficiency;

• History of organ transplant that requires the use of immunosuppressives;

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

• Poorly managed health conditions that include but are not limited to persistent or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmia, active peptic ulcer disease or gastritis, active hemorrhagic diseases, hepatitis C or human immunodeficiency virus (HIV) infection, hepatitis B (positive HBsAg and HBV DNA > 500 IU/ml), and mental disorders/social conditions that may hinder the compliance with the study requirements or the ability to give written informed consent willingly;

• Active tuberculosis;

• Receipt of live or attenuated vaccination within 30 days prior to the first dose of the investigational agents;

• History of another primary malignancy within the past 5 years, excluding adequately treated basal or squamous cell skin cancers or cervical carcinoma in situ;

• Pregnant/breastfeeding women or males/females of reproductive potential who do not use contraception.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Radiation:
• Hypofractionated radiotherapy
Participants were treated with hypofractionated radiotherapy followed by hypo-boost

Drug:
• induction chemo-immunotherapy
All participants receive two cycles of albumin-bound paclitaxel (260mg/m2) on d1 and cisplatin (25mg/m2) from d1 to d3 in combination with tislelizumab (200mg) on d1.
• concurrent chemotherapy
Concurrent chemotherapy consists of weekly albumin-bound paclitaxel (50mg/m2) and cisplatin (25mg/m2).
• Immunotheapy consolidation
Participants without disease progression, grade =3 toxicities, and/or grade =2 pneumonitis after CCRT receive tislelizumab 200 mg (Q3W) for up to 12 months.
• Thymosin Alpha1
Participants in the Ta1 treatment group will receive Ta1 from the beginning of induction chemo-immunotherapy until the completion of immunotherapy consolidation. In detail, Ta-1 would be administered according to the following three stages: Induction chemo-immunotherapy: Ta-1 will be subcutaneously administered at 4.8 mg on d1 and d3 for each cycle. Concurrent chemoradiotherapy: Ta-1 will be subcutaneously administered at 4.8mg biweekly. Immunotherpay consolidation: Ta-1 will be administered concurrently with tislelizumab at 4.8mg (Q3W) for 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 (9)

Bryant AK, Yin H, Schipper MJ, Paximadis PA, Boike TP, Bergsma DP, Movsas B, Dess RT, Mietzel MA, Kendrick R, Seferi M, Dominello MM, Matuszak MM, Jagsi R, Hayman JA, Pierce LJ, Jolly S; Michigan Radiation Oncology Quality Consortium. Uptake of Adjuvant Durvalumab After Definitive Concurrent Chemoradiotherapy for Stage III Nonsmall-cell Lung Cancer. Am J Clin Oncol. 2022 Apr 1;45(4):142-145. doi: 10.1097/COC.0000000000000899. — View Citation

Danielli R, Cisternino F, Giannarelli D, Calabro L, Camerini R, Savelli V, Bova G, Dragonetti R, Di Giacomo AM, Altomonte M, Maio M. Long-term follow up of metastatic melanoma patients treated with Thymosin alpha-1: investigating immune checkpoints synergy. Expert Opin Biol Ther. 2018 Jul;18(sup1):77-83. doi: 10.1080/14712598.2018.1494717. — View Citation

Garaci E, Pica F, Serafino A, Balestrieri E, Matteucci C, Moroni G, Sorrentino R, Zonfrillo M, Pierimarchi P, Sinibaldi-Vallebona P. Thymosin alpha1 and cancer: action on immune effector and tumor target cells. Ann N Y Acad Sci. 2012 Oct;1269:26-33. doi: 10.1111/j.1749-6632.2012.06697.x. — View Citation

Liu F, Qiu B, Xi Y, Luo Y, Luo Q, Wu Y, Chen N, Zhou R, Guo J, Wu Q, Xiong M, Liu H. Efficacy of Thymosin alpha1 in Management of Radiation Pneumonitis in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiotherapy: A Phase 2 Clinical Trial (GASTO-1043). Int J Radiat Oncol Biol Phys. 2022 Nov 1;114(3):433-443. doi: 10.1016/j.ijrobp.2022.07.009. Epub 2022 Jul 21. — View Citation

Romani L, Bistoni F, Gaziano R, Bozza S, Montagnoli C, Perruccio K, Pitzurra L, Bellocchio S, Velardi A, Rasi G, Di Francesco P, Garaci E. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 2004 Jun 1;103(11):4232-9. doi: 10.1182/blood-2003-11-4036. Epub 2004 Feb 24. — View Citation

Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Ozguroglu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2. Erratum In: J Clin Oncol. 2022 Jun 10;40(17):1965. — View Citation

Wara WM, Ammann AJ, Wara DW. Effect of thymosin and irradiation on immune modulation in head and neck and esophageal cancer patients. Cancer Treat Rep. 1978 Nov;62(11):1775-8. — View Citation

Wu J, Zhou L, Liu J, Ma G, Kou Q, He Z, Chen J, Ou-Yang B, Chen M, Li Y, Wu X, Gu B, Chen L, Zou Z, Qiang X, Chen Y, Lin A, Zhang G, Guan X. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013 Jan 17;17(1):R8. doi: 10.1186/cc11932. — View Citation

Yegya-Raman N, Friedes C, Sun L, Iocolano M, Kim KN, Doucette A, Cohen RB, Robinson KW, Levin WP, Cengel KA, Lally B, Agarwal M, D'Avella CA, Marmarelis ME, Kosteva JA, Singh AP, Ciunci CA, Aggarwal C, Berman AT, Langer CJ, Feigenberg SJ. Utilization and Factors Precluding Receipt of Checkpoint Inhibitor Consolidation for Stage III NSCLC in a Large US Academic Health System. Clin Lung Cancer. 2023 Jul;24(5):474-482. doi: 10.1016/j.cllc.2023.03.013. Epub 2023 Apr 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Completion rate of immunotherapy	Proportion of participants completing 12 months of consolidation of immutherapy	Calculated from the start of treatment to one year after the last treatment completion
Secondary	Overall survival		2 years
Secondary	Progression-free survival		one year
Secondary	Incidence of =grade 2 pneumonia		through study completion, an average of 1 year
Secondary	Drop-out rate during the I/O consolidation		One year
Secondary	The absolute count of total lymphocyte in peripheral blood	Measured at baseline, before immunotherapy, and every 3-4 months thereafter until the end of immunotherapy.	Calculated from the start of treatment to one year after the last treatment completion; up to 18 months
Secondary	The expression of peripheral blood cytokines (including IL2, IL4, IL6, IL10, TNF-a, and IFN-?)	Measured at baseline, before immunotherapy, and every 3-4 months thereafter until the end of immunotherapy.	Calculated from the start of treatment to one year after the last treatment completion; up to 18 months
Secondary	The absolute count of peripheral blood lymphocyte subsets (including CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD3-CD16+CD56+, and CD56+ NK cells, PD-1+CD8+ T cells, Tim3+ CD8+ T cells, CD62lowCD4+ T cells, PD-1+CD4+ T cells, and Tim3+CD4+ T cells	Measured at baseline, before immunotherapy, and every 3-4 months thereafter until the end of immunotherapy.	Calculated from the start of treatment to one year after the last treatment completion; up to 18 months