Nebulized Inhalation of Recombinant Human p53 Adenovirus Injection for Treatment of Multiple Ground-Glass Lung Nodules: A Single-Arm Clinical Study

NCT ID: NCT07150416

Last Updated: 2025-09-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-01

Study Completion Date

2027-02-01

Brief Summary

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This study aims to evaluate the safety and efficacy of nebulized inhalation of Recombinant Human Ad-p53 Injection (Gendicine®) for the treatment of multiple ground-glass lung nodules. This is a single-arm, open-label clinical study conducted at The First Affiliated Hospital of Guangzhou Medical University in China. We plan to enroll approximately 38 patients who have been diagnosed with multiple ground-glass nodules. All participants in this study will receive the nebulized Gendicine® treatment. After the treatment, we will monitor changes in the nodules through regular chest CT scans and record any potential treatment-related reactions to determine if this novel therapy is safe and effective. This study has been approved by the hospital's Ethics Committee.

Detailed Description

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Background: Ground-glass nodules (GGN) are a common manifestation of early-stage lung adenocarcinoma, and their management strategy (active surveillance or surgical intervention) often presents a dilemma for clinicians and patients. Gendicine® (Recombinant Human Ad-p53 Injection) is a gene therapy product approved in China. Previous studies have shown its ability to induce tumor cell apoptosis and enhance the sensitivity to radiotherapy and chemotherapy in various solid tumors. This study aims to investigate this innovative approach of local administration via nebulized inhalation for treating precancerous lesions or early-stage lung cancer.

Methods: This is a single-arm, open-label, phase II clinical trial utilizing the Simon's optimal two-stage design. The first stage plans to enroll 16 patients. If ≥1 objective response (according to RECIST 1.1 criteria) is observed, the study will proceed to the second stage, with a total planned enrollment of 30 evaluable patients (38 subjects will be recruited accounting for a 20% dropout rate). Participants are patients with multiple ground-glass nodules confirmed by imaging, with at least one nodule pathologically confirmed as malignant. The intervention is nebulized inhalation of Gendicine® at a dose of 1×10¹² VP per time, administered once every three days, for a total of four times. The primary endpoint is the Objective Response Rate (ORR), defined as the proportion of patients achieving Complete Response (CR) or Partial Response (PR) at 6 months post-treatment. Secondary endpoints include safety (assessing adverse events according to CTCAE v5.0), changes in tumor markers, and quality of life scores.

Significance: This study is the world's first clinical trial to explore nebulized inhalation of a gene therapy product for the treatment of lung nodules. Positive results would provide a novel, non-invasive treatment strategy for the very early intervention of lung cancer, potentially delaying or preventing nodule malignancy and avoiding surgical trauma.

Conditions

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Multiple Pulmonary Ground-Glass Nodules Lung Neoplasms Precancerous Conditions

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

This is a single-arm, open-label phase II trial. All enrolled participants will receive the same intervention (nebulized Gendicine®)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

This is an open-label study. No masking (blinding) was used as all participants receive the same active intervention.

Study Groups

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Gendicine Nebulization Arm

Participants in this single arm of the study will all receive the active intervention, which is Nebulized Inhalation of Recombinant Human p53 Adenovirus Injection (Gendicine®), at a dose of 1×10¹² VP per session. The treatment will be administered once every three days, for a total of four sessions.

Group Type EXPERIMENTAL

Recombinant Human Ad-p53 Injection

Intervention Type DRUG

A replication-deficient recombinant human type 5 adenovirus vector encoding the human wild-type p53 tumor suppressor gene. For this study, it will be administered via nebulized inhalation.

Interventions

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Recombinant Human Ad-p53 Injection

A replication-deficient recombinant human type 5 adenovirus vector encoding the human wild-type p53 tumor suppressor gene. For this study, it will be administered via nebulized inhalation.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ 18 years.
2. CT scan confirms the presence of multiple ground-glass nodules (GGNs), with at least one nodule measuring between 0.5 cm and 3.0 cm in diameter.
3. At least one GGN is confirmed as malignant or precancerous (e.g., atypical adenomatous hyperplasia, adenocarcinoma in situ) by histopathology or cytology.
4. Life expectancy ≥ 12 weeks.
5. Adequate pulmonary function tests (FEV1 ≥ 70% of predicted value).
6. Signed informed consent.

Exclusion Criteria

1. Pregnant or lactating women.
2. History of other active malignancies within the past 5 years.
3. Severe cardiac, hepatic, or renal dysfunction (e.g., NYHA class III/IV heart failure, ALT/AST \> 3×ULN, Cr \> 1.5×ULN).
4. Uncontrolled systemic infection or immunodeficiency diseases.
5. Participation in another interventional clinical trial within 4 weeks prior to enrollment.
6. Known hypersensitivity to any component of the recombinant human p53 adenovirus injection.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shenzhen SiBiono GeneTech Co.,Ltd

INDUSTRY

Sponsor Role collaborator

The First Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role lead

Responsible Party

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Jianxing He

Principal Investigator, Department of Thoracic Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status

Countries

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China

Central Contacts

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Jianxing He, Ph.D

Role: CONTACT

86+020-83062807

Facility Contacts

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Hengrui Liang, M.D.

Role: primary

+86 15625064712

References

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Mazzone PJ, Lam L. Evaluating the Patient With a Pulmonary Nodule: A Review. JAMA. 2022 Jan 18;327(3):264-273. doi: 10.1001/jama.2021.24287.

Reference Type BACKGROUND
PMID: 35040882 (View on PubMed)

Aoki T, Hanamiya M, Uramoto H, Hisaoka M, Yamashita Y, Korogi Y. Adenocarcinomas with predominant ground-glass opacity: correlation of morphology and molecular biomarkers. Radiology. 2012 Aug;264(2):590-6. doi: 10.1148/radiol.12111337. Epub 2012 May 31.

Reference Type BACKGROUND
PMID: 22653188 (View on PubMed)

Cheng B, Li C, Li J, Gong L, Liang P, Chen Y, Zhan S, Xiong S, Zhong R, Liang H, Feng Y, Wang R, Wang H, Zheng H, Liu J, Zhou C, Shao W, Qiu Y, Sun J, Xie Z, Liang Z, Yang C, Cai X, Su C, Wang W, He J, Liang W. The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions: insights from a single-arm, phase II trial. Signal Transduct Target Ther. 2024 Apr 19;9(1):93. doi: 10.1038/s41392-024-01799-z.

Reference Type BACKGROUND
PMID: 38637495 (View on PubMed)

Pan JJ, Zhang SW, Chen CB, Xiao SW, Sun Y, Liu CQ, Su X, Li DM, Xu G, Xu B, Lu YY. Effect of recombinant adenovirus-p53 combined with radiotherapy on long-term prognosis of advanced nasopharyngeal carcinoma. J Clin Oncol. 2009 Feb 10;27(5):799-804. doi: 10.1200/JCO.2008.18.9670. Epub 2008 Dec 22.

Reference Type BACKGROUND
PMID: 19103729 (View on PubMed)

Kastan MB, Canman CE, Leonard CJ. P53, cell cycle control and apoptosis: implications for cancer. Cancer Metastasis Rev. 1995 Mar;14(1):3-15. doi: 10.1007/BF00690207.

Reference Type BACKGROUND
PMID: 7606818 (View on PubMed)

Khoo KH, Verma CS, Lane DP. Drugging the p53 pathway: understanding the route to clinical efficacy. Nat Rev Drug Discov. 2014 Mar;13(3):217-36. doi: 10.1038/nrd4236.

Reference Type BACKGROUND
PMID: 24577402 (View on PubMed)

Hassin O, Oren M. Drugging p53 in cancer: one protein, many targets. Nat Rev Drug Discov. 2023 Feb;22(2):127-144. doi: 10.1038/s41573-022-00571-8. Epub 2022 Oct 10.

Reference Type BACKGROUND
PMID: 36216888 (View on PubMed)

Kruiswijk F, Labuschagne CF, Vousden KH. p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat Rev Mol Cell Biol. 2015 Jul;16(7):393-405. doi: 10.1038/nrm4007.

Reference Type BACKGROUND
PMID: 26122615 (View on PubMed)

Kim MP, Lozano G. Mutant p53 partners in crime. Cell Death Differ. 2018 Jan;25(1):161-168. doi: 10.1038/cdd.2017.185. Epub 2017 Nov 3.

Reference Type BACKGROUND
PMID: 29099488 (View on PubMed)

Mantovani F, Collavin L, Del Sal G. Mutant p53 as a guardian of the cancer cell. Cell Death Differ. 2019 Jan;26(2):199-212. doi: 10.1038/s41418-018-0246-9. Epub 2018 Dec 11.

Reference Type BACKGROUND
PMID: 30538286 (View on PubMed)

Other Identifiers

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rAdp53-LN001

Identifier Type: -

Identifier Source: org_study_id

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