A Phase I Study on Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of SXRN Plasmid DNA Technique in Patients With Advanced Solid Tumors

NCT06736275 | Active Not Recruiting Early Phase 1

• 1 other identifier: AA0101
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical trial is to evaluate the safety and tolerability of SXRN Plasmid DNA Technique in patients with advanced solid tumors.

Conditions

Cachexia; Advanced Cancer

Keywords

micoRNA

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) and Recommended Dose for Expansion (RDE) of SXRN

  To determine the Maximum Tolerated Dose (MTD) and Recommended Dose for Expansion (RDE) of SXRN in the treatment of advanced solid tumors

  12 months

Secondary Outcomes (5)

• Pharmacokinetic parameters of SXRN

  12 months

• Preliminary anti-tumor efficacy of SXRN

  12 months

• Weight improvement of SXRN in patients with advanced solid tumors

  12 months

• Appetite improvement of SXRN in patients with advanced solid tumors

  12 months

• Pain alleviating efficacy of SXRN in patients with advanced solid tumors

  12 months

Other Outcomes (1)

• the SXRN transcripts,its targets, and possible regulated targets

  12 months

Study Arms (1)

group

EXPERIMENTAL

In this study, three dose levels are initially formulated, namely 2mg, 4mg, and 10mg of SXRN, adopting an accelerated titration followed by the traditional "3+3" design. The first day of infusion for each dose is referred to as C1D1, with the administration of QD for 5 consecutive days, followed by a 2-day break; Each treatment cycle will last 3 weeks (21 days), and the subsequent infusion regimen, including interval, frequency and dose, may be adjusted based on the initial safety and PK parameters.

Drug: SXRN

Interventions

SXRN DRUG

SXRN is a naked plasmid DNA drug targeting miRNA. Accelerated titration and "3+3" dose escalation:In light of ethical considerations and with the aim of minimizing the number of patients possibly exposed to potentially ineffective doses, an "accelerated titration" strategy will be implemented in the early dose escalation phase (2 mg dose group) in this study, with only 1 subject enrolled. If no DLT occurs to the 3 subjects under the given dose in the DLT valuation window (the 1st cycle, 3 weeks), the study will proceed to the next dose (dose escalation in the same subject is not allowed); if one subject develops DLT, 3 additional subject s will be included to the current dose group; if ≥2 DLTs occur in the dose group with 3 or 6 subject s, the dose escalation will be stopped. The decision is made by discussion among the investigators whether to terminate the escalation or consider adjusting the dose for exploration.

group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• male or female, aged 18\~75 at the time of signing the ICF;
• patient with advanced solid tumors who have failed/cannot tolerate previous standard therapies or lack conventional effective therapies;
• at least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1);
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
• expected survival time ≥12 weeks;
• lab results and organ function tested within 7 days before the initial infusion meet the criteria below:
• Blood routine: 1)Absolute Neutrophil Count (ANC) ≥1.5×10\^9/L;2)Platlets (PLT) Count≥90×10\^9/L; 3)Hemoglobins (Hb) ≥90 g/L.
• Note: the criteria above shall still be maintained within 14 days before the initial infusion, either without the need of blood transfusion, or using supportive treatment including granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), interleukin-11 (IL-11), and erythropoietin (EPO), and etc.
• Blood biochemistry: 1)Total bilirubin (TBIL) ≤3.0 × upper limit of normal (ULN); 2)Serum creatinine (SCr) ≤1.5 × ULN or creatinine clearance (CrCl) by Cockroft Gault formula ≥50 mL/min; 3)Aspartate Amino Transferase (AST), Alanine Aminotransferase (ALT) ≤2.5×ULN; for participants with liver metastasis, AST, ALT≤5.0×ULN, and ALP≤6.0×ULN; d)Albumin (ALB) ≥30g/L.
• International Normalized Ratio (INR), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN.
• Note: for subjects receiving precautious anti-coagulation treatment, the investigator shall determine whether INR and APTT remains in a safe and effective range for treatment.
• Left Ventricular Ejection Fraction (LVEF) ≥50%.
• can understand and voluntarily sign the Informed Consent Form (ICF); must be voluntary and able to finish the study program and follow-up tests.

You may not qualify if:

• Subjects who meet any of the criteria below must not be included:
• has received any of the anti-tumor treatments below:a) received cytotoxic chemotherapy, tumor immunotherapy, anti-tumor biologics or other trail agents within 4 weeks or 5 half-times (whichever is shorter) before the initial infusion.b)received an oral small-molecule targeted anti-tumor agent within 2 weeks before the first infusion or for five half-lives(whichever was shorter).c) received anti-tumor Chinese patent medicine approved by NMPA within 2 weeks before the initial infusion.d) received more than 30% bone marrow radiotherapy or large area radiotherapy within 2 weeks before initial infusion (palliative radiotherapy at the bone or superficial lesions is acceptable).
• participated in and received an investigational drug or device clinical trial within 4 weeks before initial infusion.
• Patients who had undergone or planned to undergo major surgery or interventional therapy (excluding tumor biopsy, puncture, etc.) within 4 weeks before initial infusion.
• unrecovered from the toxic reaction caused by previous anti-tumor treatment (not recovered to ≤ grade 1 or baseline; not including toxic reactions with no safety risk as determined by the investigator, such as alopecia, asymptomatic hypothyroidism caused by immune checkpoint inhibitors that can be treated with only thyroid hormone and remains stable, and etc.).
• with clinically uncontrollable serous effusion (pleural effusion, ascites and pericardio effusion). Conditions may include: moderate or above sized effusion, received within 2 weeks before the selection or plans to receive local treatments (including drainage, peritoneal shunt, and cell-free concentrated ascites reinfusion, and etc.), or effusion obviously increased within 2 weeks after the local treatment and thus needs long-term catherterization. Candidates who meet any of the conditions above, or determined by the investigator as unsuitable, shall not be included.
• with central nervous system metastasis and show relating symptoms.
• with a history of other malignant tumors, except for those that have received radical surgery and not relapsed 5 years thereafter, such as carcinoma in situ of cervix, skin basal cell carcinoma, and etc.
• with a history of immune deficiency diseases, including acquired or congenital immunodeficiency disorders; or a history of organ transplantation, heterogeneous bone marrow transplantation, or autologous hematopoietic stem cell transplantation.
• had (non-infectious) lung inflammation / interstitial lung disease that required steroid treatment within 4 weeks before the initial infusion.
• with a history of severe cardiovascular and cerebrovascular diseases, including but not limited to:
• severe abnormalty in cardiac rhythm or conduction, such as ventricular arrhythmia requiring clinical intervention, atrioventricular block of II\~III grade, and etc.;
• cardiac insufficiency of III\~IV grade as defined by New York Heart Association(NYHA);
• acute coronary syndrome, congestive cardiac failure, aortic dissection, cerebral stroke or other grade 3 or above cardio-cerebral vascular events within 6 months before the initial infusion.
• with uncontrollable high blood pressure (systolic pressure ≥160 mmHg and/or diastolic pressure ≥100 mmHg) after treatment with anti-hypertensive drugs of stable doses.

Sponsors & Collaborators

• Jiangsu Nutai Biologics Co., Ltd: lead
• Chinese Academy of Medical Sciences: collaborator

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, 100021, China

Location

Related Publications (10)

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  PMID: 33628646 BACKGROUND

• Zhao L, Liu YW, Yang T, Gan L, Yang N, Dai SS, He F. The mutual regulation between miR-214 and A2AR signaling plays an important role in inflammatory response. Cell Signal. 2015 Oct;27(10):2026-34. doi: 10.1016/j.cellsig.2015.07.007. Epub 2015 Jul 11.

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• Takayama K, Atagi S, Imamura F, Tanaka H, Minato K, Harada T, Katakami N, Yokoyama T, Yoshimori K, Takiguchi Y, Hataji O, Takeda Y, Aoe K, Kim YH, Yokota S, Tabeta H, Tomii K, Ohashi Y, Eguchi K, Watanabe K. Quality of life and survival survey of cancer cachexia in advanced non-small cell lung cancer patients-Japan nutrition and QOL survey in patients with advanced non-small cell lung cancer study. Support Care Cancer. 2016 Aug;24(8):3473-80. doi: 10.1007/s00520-016-3156-8. Epub 2016 Mar 22.

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  PMID: 25513730 BACKGROUND

MeSH Terms

Conditions

Cachexia

Condition Hierarchy (Ancestors)

Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Thinness

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Accelerated titration and "3+3" dose escalation: This study plans to start dose escalating from 2 mg, followed by 4 mg, and 10 mg as tentatively designated escalating dose groups. An "accelerated titration" strategy will be implemented in the early dose escalation phase (2 mg dose group) in this study, with only 1 subject enrolled.

Study Record Dates

• First Submitted: December 1, 2024
• First Posted: December 16, 2024
• Study Start: September 2, 2024
• Primary Completion: February 28, 2026
• Study Completion: April 30, 2026
• Last Updated: December 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)