Thymalfasin-based PRaG Mode for Advanced Refractory Solid Tumors

Advanced Solid Tumor Clinical Trial

Official title:

Treatment of Advanced Refractory Solid Tumors Based on Precise Thymalfasin-regulated PRaG Mode: an Open-label, Prospective, Multicenter Study (PRaG 5.0 Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05790447
• Other study ID #: JD-LK-2022-151-01
• Status: Recruiting
• Phase: Phase 2
• Start date: April 1, 2023
• Est. completion date: December 2025

Study information

• Verified date: March 2023
• Source: Second Affiliated Hospital of Soochow University
• Contact: Liyuan Zhang
• Phone: 0512-67784829
• Email: zhangliyuan126[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, single-arm, Phase II investigator-initiated trial of precise thymalfasin-regulated therapy combined with hypofractionated radiotherapy, PD-1/PD-L1 inhibitor sequential GM-CSF for treatment of advanced refractory solid tumors.

Description:

One cycle of activation cycle includes： Loading dose with thymalfasin was administrated based on the absolute number of T lymphocytes.

Radiotherapy (5 or 8Gy three fractions)was administrated to a metastatic lesion.

GM-CSF 200ug was subcutaneous injected for seven days from the first day of radiotherapy PD-1/L1 inhibitor was intravenous injected within one week after radiotherapy.

At least two activation cycles were administrated. Then maintenance treatment includes： Loading dose with thymalfasin was administrated based on the absolute number of T lymphocytes.

GM-CSF 200ug was subcutaneous injected for seven days. PD-1/L1 inhibitor was intravenous injected.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subjects aged= 18 years;

2. Enrolled subjects who shall meet the criteria of recurrent or metastatic advanced solid malignant tumors, have a definite pathology diagnosis report or medical history, without definitely recommended standard treatment regimen in the guidelines, and cannot tolerate or are unwilling to receive the standard treatment regimen, and have clear, measurable metastatic lesions (>1cm);

3. Subjects who have not suffered from congestive heart failure, unstable angina, or unstable arrhythmia in the past 6 months;

4. Subjects who have the ECOG (Eastern Cooperative Oncology Group) performance status score of 0-3 and the life expectancy=3 months;

5. Subjects who have no serious abnormalities of hematopoietic functions, heart, lung, liver, kidney functions, or immune deficiency in the past;

6. Subjects whose AST and ALT levels are =3.0 times the upper limit of normal (=5.0 times the upper limit of normal for patients with liver cancer/metastasis liver carcinoma), and creatinine level is =3.0 times the upper limit of normal one week before enrollment.

7. Subjects who shall have the ability to understand and voluntarily sign the informed consent forms.

Exclusion Criteria:

1. Pregnant or lactating women.

2. Subjects who have a history of other malignant diseases in the last 5 years, expect for:malignancies that can be cured after treatment (including but not limited to adequately treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer).

3. Subjects who have a history of uncontrolled epilepsy, CNS disease or mental disorder.

4. Subjects with clinically severe (active) cardiac disease such as symptomatic coronary heart disease, NYHA Class II or worse congestive heart failure, or severe arrhythmias requiring medical intervention, or a history of myocardial infarction within the last 12 months.

5. Subjects who require immunosuppressive therapy for organ transplantation.

6. Subjects with known significant active infection or significant disorders of blood, kidney, metabolism, gastrointestinal, endocrine functions or metabolisms as judged by the Investigator, or other severe, uncontrolled concomitant diseases.

7. Subjects who are allergic to any ingredient of the investigational drug.

8. Subjects who have a medical history of immunodeficiency, including HIV-positive or other acquired or congenital immunodeficiency diseases, or those with a history of organ transplantation, or those with other immune-related diseases requiring long-term oral hormone therapy.

9. Subjects who are in the stage of acute and chronic tuberculosis infections (positive result of T-spot test, with suspected tuberculous lesions on chest X-ray).

10. Other conditions that are not suitable for enrollment in the Investigator's opinions.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms
• Refractory Tumor

Intervention

Drug:
• Thymalfasin
loading dose with thymalfasin based on the amounts of T lymphocyte

Radiation:
• Radiotherapy
hypofractionated radiotherapy/SBRT

Drug:
• PD-1/PD-L1 inhibitor
The PD-1/PD-L1 inhibitors are used within one week after radiotherapy
• GM-CSF
subcutaneous injection daily for 7 consecutive days

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of SchoowUniversity	Suzhou

Sponsors (2)

Lead Sponsor	Collaborator
Second Affiliated Hospital of Soochow University	SciClone Pharmaceuticals

Country where clinical trial is conducted

China, 

References & Publications (4)

Giacomini E, Severa M, Cruciani M, Etna MP, Rizzo F, Pardini M, Scagnolari C, Garaci E, Coccia EM. Dual effect of Thymosin alpha 1 on human monocyte-derived dendritic cell in vitro stimulated with viral and bacterial toll-like receptor agonists. Expert Op — View Citation

Kong Y, Zhao X, Xu M, Pan J, Ma Y, Zou L, Peng Q, Zhang J, Su C, Xu Z, Zhou W, Peng Y, Yang J, Zhou C, Li Y, Guo Q, Chen G, Wu H, Xing P, Zhang L. PD-1 Inhibitor Combined With Radiotherapy and GM-CSF (PRaG) in Patients With Metastatic Solid Tumors: An Ope — 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: — View Citation

Schulof RS, Lloyd MJ, Cleary PA, Palaszynski SR, Mai DA, Cox JW Jr, Alabaster O, Goldstein AL. A randomized trial to evaluate the immunorestorative properties of synthetic thymosin-alpha 1 in patients with lung cancer. J Biol Response Mod. 1985 Apr;4(2):1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR)	ORR is defined as the proportion of patients who have a partial (PR) or complete response (CR) to therapy among the total number of evaluable patients.	24 months
Secondary	Disease control rate (DCR)	the percentage of patients who have achieved complete response (CR), partial response (PR) and stable disease (SD)	24 months
Secondary	Progression free survival (PFS)	The time from commencement of treatment to disease progression or death from any cause.	24 months
Secondary	Overall survival (OS)	The time from the first day of enrollment to death from any cause.	24 months
Secondary	Incidence of adverse events	the rate of AE	24 months