Serum Exosomal miRNA Predicting the Therapeutic Efficiency in Lung Squamous Carcinoma

Squamous Cell Carcinoma Clinical Trial

Official title:

A Study on Serum Exosomal miRNA Predicting the Effective and Prognosis of Immunotherapy Combined With Chemotherapy in Pulmonary Squamous Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05854030
• Other study ID #: SCC-EV-2022
• Status: Recruiting
• Start date: April 1, 2022
• Est. completion date: August 31, 2023

Study information

• Verified date: March 2023
• Source: Tianjin Medical University Cancer Institute and Hospital
• Contact: Richeng Jiang, Postdoctor
• Phone: 862223340123
• Email: jiangricheng[@]tjmuch.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is an observational prospective bi-center study of 50 patients operated on advanced squamous cell carcinoma. The main aim is to investigate the efficacy of serum exosomal miRNA as a biomarker for predicting the therapeutic effect of immunotherapy combined with chemotherapy.

Description:

PD-L1 Testing in guiding patient selection for PD-1/PD-L1 inhibitor therapy in Lung Cancer exhibits insufficient sensitivity and efficacy. The investigators aimed to identify specific serum exosomal miRNA biomarkers that are highly sensitive and stable for predicting the therapeutic effect of immunotherapy combined with chemotherapy. So that the clinicians could use the biomarker to better stratify patients and select potential immunotherapy-beneficial subgroups before clinical decisions.

We plan to enroll 50 patients with advanced treatment-naïve squamous cell carcinoma and 10 healthy people in the present study. Peripheral blood from the plasma of 10 healthy individuals and 50 pulmonary squamous cell carcinoma (SCC) patients will be collected before first-line treatment and after 2 cycles of anti-PD-L1 immunotherapy combined with chemotherapy.

Firstly, exosomal miRNAs extracted from peripheral blood will be analyzed through high-throughput RNA sequencing to identify specific exosomal miRNAs.

Secondly, through analyzing the PFS and OS follow-up data of patients, they are divided into different subgroups. We explore the value of early predicting efficacy of exosome miRNA basing on sequencing results.

Thirdly, we compared the exo-miRNA biomarker with the value of PD-L1 expression in predicting the efficacy of immunotherapy.

Lastly, we suggest exo-miRNA combined with PD-L1 as a biomarker combination in predicting anti-PD-L1 immunotherapy efficacy to better select the potential benefit population suitable for immunotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: August 31, 2023
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histology or cytology confirmed patients with stage IV squamous cell carcinoma of IASLC TNM (8th edition);

2. Patients have not previously received first-line anti-tumor systemic therapy for advanced lung cancer;

3. At least one measurable lesion according to the irRECIST 1.1 standard;

4. Physical condition and organ function allow for systemic antitumor therapy, including standard chemotherapy and immunotherapy;

5. Age = 18 years at the time of signing the informed consent form;

6. Estimated survival= 3 months;

7. Patients can follow the planned schedule and actively cooperate in returning to the hospital for regular clinical follow-up and necessary treatment;

8. It can provide the clinical data required for research and is willing to use the test data for further scientific research and commercial product development.

Exclusion Criteria:

1. Other malignancies within the last 5 years (except adequately treated carcinoma in situ and basal or squamous cell skin cancer);

2. The investigators judged that the patient also had other serious medical conditions that could affect follow-up and short-term survival;

3. Any other medical condition and social/psychological problems which the investigator determines that the patient is not suitable to participate in this study;

4. Contrast-enhanced MRI or contrast-enhanced CT for clinical follow-up is not acceptable;

5. Have an active or previous auto-immune disease that is likely to recur;

6. Other antineoplastic therapies were planned for the duration of the study.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Exosomes
• Lung Neoplasm
• Lung Neoplasms
• Squamous Cell Carcinoma

Intervention

Diagnostic Test:
• collect plasma samples and clinical features
8ml of peripheral blood need to be collected from pre- and post-treatment advanced pulmonary squamous carcinoma separately

Locations

Country	Name	City	State
China	TianjinCIH	Tianjin	Tianjin

Sponsors (2)

Lead Sponsor	Collaborator
Tianjin Medical University Cancer Institute and Hospital	Tianjin Chest Hospital

Country where clinical trial is conducted

China, 

References & Publications (11)

Cazzoli R, Buttitta F, Di Nicola M, Malatesta S, Marchetti A, Rom WN, Pass HI. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol. 2013 Sep;8(9):1156-62. doi: 10.1097/JTO.0b013e31 — View Citation

Cordonnier M, Nardin C, Chanteloup G, Derangere V, Algros MP, Arnould L, Garrido C, Aubin F, Gobbo J. Tracking the evolution of circulating exosomal-PD-L1 to monitor melanoma patients. J Extracell Vesicles. 2020 Jan 7;9(1):1710899. doi: 10.1080/20013078.2 — View Citation

Correction: Correlation of plasma exosomal microRNAs with the efficacy of immunotherapy in EGFR / ALK wild-type advanced non-small cell lung cancer. J Immunother Cancer. 2020 May;8(1):e000376corr1. doi: 10.1136/jitc-2019-000376corr1. No abstract available — View Citation

Hansen AR, Siu LL. PD-L1 Testing in Cancer: Challenges in Companion Diagnostic Development. JAMA Oncol. 2016 Jan;2(1):15-6. doi: 10.1001/jamaoncol.2015.4685. No abstract available. — View Citation

Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang S — View Citation

Mashouri L, Yousefi H, Aref AR, Ahadi AM, Molaei F, Alahari SK. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer. 2019 Apr 2;18(1):75. doi: 10.1186/s12943-019-0991-5. — View Citation

Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, Miller ML, Rekhtman N, Moreira AL, Ibrahim F, Bruggeman C, Gasmi B, Zappasodi R, Maeda Y, Sander C, Garon EB, Merghoub T, Wolchok JD, Schumacher TN, Chan TA. — View Citation

Sacher AG, Gandhi L. Biomarkers for the Clinical Use of PD-1/PD-L1 Inhibitors in Non-Small-Cell Lung Cancer: A Review. JAMA Oncol. 2016 Sep 1;2(9):1217-22. doi: 10.1001/jamaoncol.2016.0639. — View Citation

Walsh RJ, Soo RA. Resistance to immune checkpoint inhibitors in non-small cell lung cancer: biomarkers and therapeutic strategies. Ther Adv Med Oncol. 2020 Jul 3;12:1758835920937902. doi: 10.1177/1758835920937902. eCollection 2020. — View Citation

Yu W, Hurley J, Roberts D, Chakrabortty SK, Enderle D, Noerholm M, Breakefield XO, Skog JK. Exosome-based liquid biopsies in cancer: opportunities and challenges. Ann Oncol. 2021 Apr;32(4):466-477. doi: 10.1016/j.annonc.2021.01.074. Epub 2021 Feb 4. — View Citation

Zhang C, Chong X, Jiang F, Gao J, Chen Y, Jia K, Fan M, Liu X, An J, Li J, Zhang X, Shen L. Plasma extracellular vesicle derived protein profile predicting and monitoring immunotherapeutic outcomes of gastric cancer. J Extracell Vesicles. 2022 Apr;11(4):e — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	plasma exosomal miRNA level	The expression levels of serum exosome micro RNA	Baseline up to 21 days
Primary	PD-L1	the expression levels of PD-L1	Baseline up to 21 days
Primary	Imaging data of lesions	Imaging data of the pulmonary and metastatic lesions of the patients are collected	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Primary	Objective response rate		From the start of systemic treatment date until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 100 months