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NCT05790447·Phase 2·INTERVENTIONAL

Thymalfasin-based PRaG Mode for Advanced Refractory Solid Tumors

Status

Unknown

Phase

Phase 2

Enrollment

60

Locations

1

Results

Not posted

Publications

5

Study summary

What the protocol is testing.

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.

Full detailed 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.

Interventions

Treatment arms and agents.

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

DRUG

GM-CSF

subcutaneous injection daily for 7 consecutive days

Timeline

From registration to results.

  1. First posted

    Mar 30, 2023

  2. Study start

    Apr 1, 2023

  3. Primary completion

    May 2025

  4. Study completion

    Dec 2025

  5. Results posted

    Not reported

  6. Registry updated

    Mar 30, 2023

Outcomes

What the study measures.

Primary outcomes

Overall response rate (ORR)

Time frame · 24 months

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.

Secondary outcomes

Disease control rate (DCR)

Time frame · 24 months

the percentage of patients who have achieved complete response (CR), partial response (PR) and stable disease (SD)

Progression free survival (PFS)

Time frame · 24 months

The time from commencement of treatment to disease progression or death from any cause.

Overall survival (OS)

Time frame · 24 months

The time from the first day of enrollment to death from any cause.

Incidence of adverse events

Time frame · 24 months

the rate of AE

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
Not reported
Sex
ALL
Healthy volunteers
No

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.

Study locations

1 registered sites.

China. Showing up to 24 locations stored in the fast local snapshot.

The Second Affiliated Hospital of SchoowUniversity

Suzhou, China

Publications

Results and literature.

PMID 35874780Kong 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 Open-Label Phase II Study. Front Immunol. 2022 Jul 8;13:952066. doi: 10.3389/fimmu.2022.952066. eCollection 2022.PMID 26096650Giacomini 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 Opin Biol Ther. 2015;15 Suppl 1:S59-70. doi: 10.1517/14712598.2015.1019460. Epub 2015 Jun 22.PMID 3998766Schulof 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):147-58.PMID 35870709Liu 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.PMID 38458816Kong Y, Chen R, Xu M, Zhang J, Chen G, Hong Z, Zhang H, Dai X, Ma Y, Zhao X, Peng Y, Zhang C, Xing P, Zhang L. Evaluation of the efficacy and safety of a precise thymalfasin-regulated PRaG regimen for advanced refractory solid tumours: protocol for the open-label, prospective, multicentre study (PRaG5.0 study). BMJ Open. 2024 Mar 8;14(3):e075642. doi: 10.1136/bmjopen-2023-075642.

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