Thymalfasin-based PRaG Mode for Advanced Refractory Solid Tumors

NCT05790447 | Unknown Phase 2

• 1 other identifier: JD-LK-2022-151-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Solid Tumor; Refractory Tumor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Disease control rate (DCR)

  24 months

• Progression free survival (PFS)

  24 months

• Overall survival (OS)

  24 months

• Incidence of adverse events

  24 months

Study Arms (1)

Intervention group

EXPERIMENTAL

A treatment 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

Drug: Thymalfasin; Radiation: Radiotherapy; Drug: PD-1/PD-L1 inhibitor; Drug: GM-CSF

Interventions

Thymalfasin DRUG

loading dose with thymalfasin based on the amounts of T lymphocyte

Also known as: Thymosin alpha-1

Intervention group

Radiotherapy RADIATION

hypofractionated radiotherapy/SBRT

Intervention group

PD-1/PD-L1 inhibitor DRUG

The PD-1/PD-L1 inhibitors are used within one week after radiotherapy

Also known as: PD-1/PD-L1 antibody

Intervention group

GM-CSF DRUG

subcutaneous injection daily for 7 consecutive days

Also known as: :Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor for Injection

Intervention group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged≥ 18 years;
• 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);
• Subjects who have not suffered from congestive heart failure, unstable angina, or unstable arrhythmia in the past 6 months;
• Subjects who have the ECOG (Eastern Cooperative Oncology Group) performance status score of 0-3 and the life expectancy≥3 months;
• Subjects who have no serious abnormalities of hematopoietic functions, heart, lung, liver, kidney functions, or immune deficiency in the past;
• 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.
• Subjects who shall have the ability to understand and voluntarily sign the informed consent forms.

You may not qualify if:

• Pregnant or lactating women.
• 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).
• Subjects who have a history of uncontrolled epilepsy, CNS disease or mental disorder.
• 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.
• Subjects who require immunosuppressive therapy for organ transplantation.
• 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.
• Subjects who are allergic to any ingredient of the investigational drug.
• 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.
• 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).
• Other conditions that are not suitable for enrollment in the Investigator's opinions.

Sponsors & Collaborators

• Second Affiliated Hospital of Soochow University: lead
• SciClone Pharmaceuticals: collaborator

Study Sites (1)

The Second Affiliated Hospital of SchoowUniversity

Suzhou, 215004, China

RECRUITING

Related Publications (5)

• 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 Open-Label Phase II Study. Front Immunol. 2022 Jul 8;13:952066. doi: 10.3389/fimmu.2022.952066. eCollection 2022.

  PMID: 35874780 RESULT

• 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 Opin Biol Ther. 2015;15 Suppl 1:S59-70. doi: 10.1517/14712598.2015.1019460. Epub 2015 Jun 22.

  PMID: 26096650 RESULT

• 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):147-58.

  PMID: 3998766 RESULT

• 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.

  PMID: 35870709 RESULT

• Kong 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.

  PMID: 38458816 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Thymalfasin; Radiotherapy; Immune Checkpoint Inhibitors; Granulocyte-Macrophage Colony-Stimulating Factor; Macrophage Colony-Stimulating Factor; Injections

Intervention Hierarchy (Ancestors)

Thymosin; Thymus Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Biological Factors; Drug Administration Routes; Drug Therapy

Central Study Contacts

Liyuan Zhang

CONTACT

0512-67784829; zhangliyuan126@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2023
• First Posted: March 30, 2023
• Study Start: April 1, 2023
• Primary Completion: May 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 30, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)