The Impact of Thymosin α-1 on the Efficacy of Concurrent Chemoradiotherapy Followed by Immunotherpay Consolidation for Locally Advanced NSCLC
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Concurrent Tα-1 group In this concurrent Tα-1 group, participants receive concurrent chemoradiotherapy followed by immunotherapy consolidation. During this treatment, thymosin alpha-1 was administered at 4.8mg each time. |
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.
Other Names:
Drug: concurrent chemotherapy
Concurrent chemotherapy consists of weekly albumin-bound paclitaxel (50mg/m2) and cisplatin (25mg/m2).
Other Names:
Drug: 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.
Other Names:
Drug: Thymosin Alpha1
Participants in the Tα1 treatment group will receive Tα1 from the beginning of induction chemo-immunotherapy until the completion of immunotherapy consolidation. In detail, Tα-1 would be administered according to the following three stages:
Induction chemo-immunotherapy: Tα-1 will be subcutaneously administered at 4.8 mg on d1 and d3 for each cycle.
Concurrent chemoradiotherapy: Tα-1 will be subcutaneously administered at 4.8mg biweekly.
Immunotherpay consolidation: Tα-1 will be administered concurrently with tislelizumab at 4.8mg (Q3W) for up to 12 months.
Other Names:
|
| Other: Control group In control group, participants receive concurrent chemoradiotherapy followed by immunotherapy consolidation. |
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.
Other Names:
Drug: concurrent chemotherapy
Concurrent chemotherapy consists of weekly albumin-bound paclitaxel (50mg/m2) and cisplatin (25mg/m2).
Other Names:
Drug: 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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Completion rate of immunotherapy [Calculated from the start of treatment to one year after the last treatment completion]
Proportion of participants completing 12 months of consolidation of immutherapy
Secondary Outcome Measures
- Overall survival [2 years]
- Progression-free survival [one year]
- Incidence of ≥grade 2 pneumonia [through study completion, an average of 1 year]
- Drop-out rate during the I/O consolidation [One year]
- The absolute count of total lymphocyte in peripheral blood [Calculated from the start of treatment to one year after the last treatment completion; up to 18 months]
Measured at baseline, before immunotherapy, and every 3-4 months thereafter until the end of immunotherapy.
- The expression of peripheral blood cytokines (including IL2, IL4, IL6, IL10, TNF-α, and IFN-γ) [Calculated from the start of treatment to one year after the last treatment completion; up to 18 months]
Measured at baseline, before immunotherapy, and every 3-4 months thereafter until the end of immunotherapy.
- 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 [Calculated from the start of treatment to one year after the last treatment completion; up to 18 months]
Measured at baseline, before immunotherapy, and every 3-4 months thereafter until the end of immunotherapy.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
aged ≥18 years old
-
histologically confirmed locally advanced and unresectable NSCLC;
-
no prior radiotherapy or surgery;
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with the life expectancy over 12 weeks;
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
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adequate bone marrow and hepatic and renal functions;
-
informed consent
Exclusion Criteria:
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Concurrent enrollment in another clinical trial, unless it is an observational (non-interventional) clinical study;
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With histologically documented combined small-cell lung carcinoma;
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Major surgery (excluding vascular access placement) within 4 weeks prior to enrollment in the study;
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Active or prior documented autoimmune disease within the past 2 years;
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Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis);
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History of innate immunodeficiency;
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History of organ transplant that requires the use of immunosuppressives;
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A mean heart rate-corrected QT interval (QTc) ≥ 470 ms, calculated using Bazett correction from 3 ECG calculation cycles;
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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;
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Active tuberculosis;
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Receipt of live or attenuated vaccination within 30 days prior to the first dose of the investigational agents;
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History of another primary malignancy within the past 5 years, excluding adequately treated basal or squamous cell skin cancers or cervical carcinoma in situ;
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Pregnant/breastfeeding women or males/females of reproductive potential who do not use contraception.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sun yat-sen university cancer center | Guangzhou | Guangdong | China | 510000 |
Sponsors and Collaborators
- Sun Yat-sen University
Investigators
- Principal Investigator: Hui Liu, Professor, Sun Yat-sen University
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- GASTO-1098