Precision Treatment of Recurrent/Metastatic Salivary Gland Carcinoma Guided by Molecular Typing

Official title

Cancer Hospital, Chinese Academy of Medical Sciences/National Cancer Center of China

Overview

Patients with salivary gland carcinoma were divided into groups according to HER2, NTRK, AR, TROP-2, etc. Patients in different groups were given precision targeted therapy or chemotherapy to evaluate the efficacy (ORR rate) and safety of precision therapy.

Detailed description

Patients with locally advanced/recurrent or oligometastatic salivary gland carcinoma will be stratified by HER2, NTRK, AR, TROP-2, etc., and receive precision-targeted or chemotherapy regimens, with efficacy (objective response rate, etc.) and safety of neoadjuvant/conversion therapy evaluated.

To assess the efficacy of post-operative adjuvant therapy guided by minimal residual disease (MRD) testing in locally advanced salivary gland carcinoma.

Patients with locally advanced/recurrent or symptomatic, rapidly progressive metastatic salivary gland carcinoma who are intolerant of or refuse surgery and radiotherapy will be molecularly stratified and treated with precision regimens, with efficacy (objective response rate, etc.) and safety of salvage therapy evaluated.

To evaluate efficacy (objective response rate, etc.) and safety of later-line therapy for locally advanced/recurrent or distant metastatic salivary gland carcinoma.

Using multi-omic approaches to explore salivary gland carcinoma heterogeneity and biomarkers associated with recurrence, metastasis, treatment response and prognosis.

To investigate concordance between drug-sensitivity testing using ex-vivo 3D tumour models and actual clinical outcomes, and to guide later-line treatment selection based on drug-sensitivity results.

The diagnostic and prognostic value of fibroblast activation protein inhibitor (FAPI) PET/CT for salivary gland cancer: All patients undergo routine standard examinations (FDG PET/CT) and FAPI PET/CT before and after treatment. Two independent blinded reading teams separately evaluate the two sets of images to provide diagnosis, staging, and follow-up on patient prognosis.

Interventions

• Drug Cohort 1 (HER2-positive, RC48-ADC)
  Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. Adjuvant phase: Treatment i
• Drug Cohort 2 (NTRK-fusion or NTRK-mutant)
  Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. Adjuvant phase: Treatment i
• Drug Cohort 3 (AR-positive, leuprolide + bicalutamide + abiraterone)
  Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. Adjuvant phase: Treatment i
• Drug TROP2 ADC
  Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. Adjuvant phase: Treatment i
• Drug TKI
  Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. Adjuvant phase: Treatment i
• Drug Albumin-paclitaxel + platinum
  Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. Adjuvant phase: Treatment i
• Drug Albumin-paclitaxel + carboplatin + apatinib + camrelizumab
  Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. Adjuvant phase: Treatment i
• Drug albumin-bound paclitaxel+trastuzumab+pyrotinib
  Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. Adjuvant phase: Treatment i
• Drug HER2,trastuzumab deruxtecan± pertuzumab
  Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. Adjuvant phase: Treatment i
• Drug AR,AR antagonist ++ goserelin + pertuzumab + trastuzumab
  Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. Adjuvant phase: Treatment i

Primary outcome measures

• ORR [Time frame: ORR at the end of Cycle 2 (each cycle is 21 days)]

Secondary outcome measures (6)

• MPR; [Time frame: MPR rate at the end of surgical treatment]
• R0 resection rate; [Time frame: R0 resection rate at the end of surgical treatment]
• Facial nerve protection rate [Time frame: Facial nerve protection rate at the end of surgical treatment]
• DFS [Time frame: DFS rates at 3-year]
• PFS; [Time frame: PFS Rate at 2-Year]
• OS [Time frame: OS rate at 5-year]

Eligibility criteria

Inclusion criteria

• Patients with histopathologic diagnosis of salivary gland carcinoma

• The tumor tissues were subjected to HER2/NTRK/AR/TROP-2 immunohistochemical staining.

• ECOG physical status 0 or 1 score in the 3 days before the first medication of the study treatment;

• Age 18 or older - no upper limit;

• Life expectancy is more than 3 months; ⑥Have at least one measurable lesion according to RECIST1.1 standards; ⑦Women of childbearing age must have a negative pregnancy test within 7 days before the first medication, and agree to receive the necessary contraceptive measures;

⑧The patient must have adequate liver, kidney, bone marrow, heart and lung and other organ functions:

⑨Understanding and voluntarily signing informed consent prior to performing any research-related evaluation/operation;

⑩Ability to comply with research visit schedules and other programmatic requirements.

Exclusion criteria

• Known hypersensitivity or delayed anaphylaxis to any agents in this trial;

• Major surgery had been performed within 4 weeks prior to the start of the study and did not fully recover;

• Have received a live vaccine within 4 weeks before the start of the study or plan to receive any vaccine during the study period ;

• To study the occurrence of arterial/venous thrombosis events within 6 months before medication;

• Major cardiovascular diseases;

• Is suffering from uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, cirrhosis, etc.;

• Is suffering from an active infection that requires systemic treatment;

• History of active tuberculosis; ⑨ Positive human immunodeficiency virus (HIV) test result; ⑩ Patients with chronic hepatitis B or active hepatitis C. ⑪Conditions that the investigator believes will affect the safety or compliance of the drug therapy in this study ⑫Female/male who is pregnant or breastfeeding or who intends to give birth;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 2 centers

• Fei Ma — Beijing
• National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chine — Beijing

Identifiers

NCT: NCT06145308 · NCC4132

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗