PDO Based Drug Sensitive Test in R/M SGC

NCT ID: NCT06686979

Last Updated: 2025-09-03

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-03-26
• Study Completion Date: 2028-11-30

Brief Summary

To evaluate the consistency of drug efficacy between the clinical systemic treatment and drug sensitive test based on patient-derived organoid in R/M SGC patients, using a prospective and multicenter observational study to increase the generalizability and reliability of research conclusion.

Detailed Description

Salivary gland cancer (SGC) is one type of head and neck cancer, accounting for about 5% of all head and neck tumors and less than 0.5% of all cancers, making it relatively rare. SGC originates from the salivary glands and can involve the three major salivary glands (parotid, submandibular, and sublingual glands) as well as the minor salivary glands distributed throughout the oral cavity. For early to mid-stage SGC, surgery ± radiotherapy is the main treatment; for recurrent or metastatic (R/M) SGC, palliative treatment is required, symptomatic or rapidly progressive disease should take systemic therapy into account. R/M SGC is highly heterogeneous, however, high-quality evidence-based evidence related to drug treatment is still insufficient. Individualized drug treatment needs to determine the specific treatment plan according to the characteristics of the patient and the tumor. In addition to NGS sequencing, high-throughput models for in vitro drug sensitive tests are an effective means to improve clinical efficacy.

Organoids are in vitro cultured micro-organs with 3D structures, capable of spontaneous self-renewal, self-organization, and differentiation to form complex structures similar to real tissues, partially simulating the physiological functions of the source tissue or organ. Compared with other in vitro and in vivo models such as cell lines and patient-derived xenograft models, organoid models have unique advantages: they can more vividly retain the phenotypic, genetic, and functional characteristics of the original tissue, and have a short modeling cycle, high cost-performance ratio, and can achieve high throughput drug sensitive test. In 2018, a study showed that ex vivo drug sensitivity testing based on gastrointestinal tumor organoids has a very high predictive value for clinical efficacy, with a sensitivity of 100%, specificity of 93%, and positive and negative predictive values of 88% and 100%, respectively. In addition, cancer organoids have been developed from many other cancer types and its feasibility in guiding precision medicine is investigated. The aim of present study is to evaluate the consistency of drug efficacy between the clinical systemic treatment and drug sensitive test based on patient-derived organoid in R/M SGC patients. A prospective and multicenter observational study is planned to increase the generalizability and reliability of research conclusion.

The patients with R/M SGC would receive drug treatment according to the clinical guideline or doctor's experience, at the same time, tumor biopsy samples would be collected to establish PDO for drug sensitive test. Fifteen different drug regimens sensitive test would be performed, including the actual drug regimens that the patients clinically receive, and the corresponding ex vivo tumor inhibition rate would be recorded. After the patients received the clinical treatment, they would be followed up to collect the objective response rate (ORR), disease control rate (DCR), progression-free survival time (PFS), and overall survival time (OS). Finally, the consistency of drug efficacy would be evaluated between clinical systemic treatment and drug sensitive test based on patient-derived organoid.

Conditions

Salivary Gland Cancers; Patient Derived Organoid; Drug Sensitive Test in Vitro

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Observational cohort

The observational group of patients with R/M SGC would receive drug treatment according to the clinical guideline or doctor's experience. No intervention would be provided based on the drug sensitive test from patient-derived organoid.

No Intervention: Observational Cohort

Intervention Type: OTHER

The patients with R/M SGC would receive drug treatment according to the clinical guideline or doctor's experience, at the same time, tumor biopsy samples would be collected to establish PDO for drug sensitive test. But no intervention would be used based on the PDO drug sensitive test.

Interventions

No Intervention: Observational Cohort

The patients with R/M SGC would receive drug treatment according to the clinical guideline or doctor's experience, at the same time, tumor biopsy samples would be collected to establish PDO for drug sensitive test. But no intervention would be used based on the PDO drug sensitive test.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Pathologically confirmed R/M SGC patients
• Tumor tissues available for organoid culture
• ECOG score: 0-2 points
• Life expectancy > 3 months
• Normal major organ function, tolerable to chemotherapy, targeted therapy, immunotherapy: a. Hematology examination criteria must meet: WBC≥4.0×109/L, ANC≥1.5×109/L, PLT≥80×109/L, Hb≥90 g/L (no blood transfusion or blood products within 14 days, no use of G-CSF or other hematopoietic growth factors); b. Biochemical examination must meet the following criteria: serum albumin≥3.0 g/dL (30 g/L), TBIL≤1.5×ULN, ALT, AST≤2.5×ULN, BUN and CRE≤1.5×ULN or endogenous creatinine clearance≥60 ml/min (Cockcroft-Gault formula); c. Good coagulation function: defined as International Normalized Ratio (INR) or Prothrombin Time (PT)≤1.5 times ULN; if the study participant is on anticoagulant therapy, as long as PT is within the intended range of the anticoagulant medication
• Able to understand the content of informed consent form, sign the informed consent form, and willing to cooperate with the follow-up

Exclusion Criteria

• Metastatic tumors in the head and neck region, or non-salivary gland cancer tumors such as sarcoma, squamous cell carcinoma, nasopharyngeal carcinoma, etc.
• Known allergy to the study drugs or their active ingredients or any excipients; or had a severe allergic reaction to other monoclonal antibodies
• Pregnant or breastfeeding female patients; or women of childbearing age with positive pregnancy test results (serum or urine) within 7 days before enrollment, or negative results but refusing to use effective contraception during the study period and 2 months after the last administration of study medication; or male patients with partners of childbearing age, refusing to use effective contraception during the study period and 2 months after the last administration of study medication
• Severe liver diseases (such as cirrhosis), kidney diseases, respiratory system diseases, hematopoietic system diseases, or endocrine system diseases, uncontrolled diseases
• Infected with HIV, active hepatitis B (HBV-DNA≥104 copies/ml) or hepatitis C (hepatitis C antibody positive, and HCR-RNA above the lower limit of detection of the analytical method), uncontrolled diseases
• Within 6 months before enrollment, the following conditions occurred: myocardial infarction, severe/unstable angina, NYHA class 2 or above heart failure, clinically significant supraventricular or ventricular arrhythmias, and symptomatic congestive heart failure, uncontrolled diseases
• Patients with mental illness or known history of psychiatric drug abuse or drug addiction
• Unable to give consent, unable to obtain the required amount of tumor tissue for the study
• Other serious physical or mental diseases or laboratory test abnormalities that may increase the risk of participating in the study or interfere with the study results; or any other situation that the researchers deem unsuitable for participation in this study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Cancer Hospital, China

OTHER

Sponsor Role: collaborator

Eye & ENT Hospital of Fudan University

OTHER

Sponsor Role: collaborator

Dongfang Hospital Affiliated to Tongji University

OTHER

Sponsor Role: collaborator

Shandong Cancer Hospital and Institute

OTHER

Sponsor Role: collaborator

Qilu Hospital of Shandong University

OTHER

Sponsor Role: collaborator

Shandong Provincial Hospital

OTHER_GOV

Sponsor Role: collaborator

Hospital of Stomatology, Wuhan University

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: collaborator

Zhejiang University

OTHER

Sponsor Role: collaborator

Sir Run Run Shaw Hospital

OTHER

Sponsor Role: collaborator

Zhejiang Cancer Hospital

OTHER

Sponsor Role: collaborator

Shanghai Huangpu District Central Hospital

UNKNOWN

Sponsor Role: collaborator

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: collaborator

Wuhan TongJi Hospital

OTHER

Sponsor Role: collaborator

Zhongnan Hospital

OTHER

Sponsor Role: collaborator

Huashan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Lai-ping Zhong

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lai-ping Zhong, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Huashan Hospital

Locations

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Site Status: ACTIVE_NOT_RECRUITING

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lai-ping Zhong, MD, PhD

Role: CONTACT

zhonglp@hotmail.com

+862152888915

Tong-chao Zhao, MD, PhD

Role: CONTACT

961497591@qq.com

+862152889999 ext. 7182

Facility Contacts

Lai-ping Zhong, MD, PhD

Role: primary

zhonglp@hotmail.com

+862152888915

Tong-chao Zhao, MD, PhD

Role: backup

961497591@qq.com

+862152889999 ext. 7182

References

Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernandez-Mateos J, Khan K, Lampis A, Eason K, Huntingford I, Burke R, Rata M, Koh DM, Tunariu N, Collins D, Hulkki-Wilson S, Ragulan C, Spiteri I, Moorcraft SY, Chau I, Rao S, Watkins D, Fotiadis N, Bali M, Darvish-Damavandi M, Lote H, Eltahir Z, Smyth EC, Begum R, Clarke PA, Hahne JC, Dowsett M, de Bono J, Workman P, Sadanandam A, Fassan M, Sansom OJ, Eccles S, Starling N, Braconi C, Sottoriva A, Robinson SP, Cunningham D, Valeri N. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science. 2018 Feb 23;359(6378):920-926. doi: 10.1126/science.aao2774.

Reference Type: BACKGROUND

PMID: 29472484 (View on PubMed)

Pasch CA, Favreau PF, Yueh AE, Babiarz CP, Gillette AA, Sharick JT, Karim MR, Nickel KP, DeZeeuw AK, Sprackling CM, Emmerich PB, DeStefanis RA, Pitera RT, Payne SN, Korkos DP, Clipson L, Walsh CM, Miller D, Carchman EH, Burkard ME, Lemmon KK, Matkowskyj KA, Newton MA, Ong IM, Bassetti MF, Kimple RJ, Skala MC, Deming DA. Patient-Derived Cancer Organoid Cultures to Predict Sensitivity to Chemotherapy and Radiation. Clin Cancer Res. 2019 Sep 1;25(17):5376-5387. doi: 10.1158/1078-0432.CCR-18-3590. Epub 2019 Jun 7.

Reference Type: BACKGROUND

PMID: 31175091 (View on PubMed)

Other Identifiers

DST-PDO-SGC

Identifier Type: -

Identifier Source: org_study_id