Salivary Gland Carcinoma, Precision Therapy
Conditions
Brief summary
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
DRUGCohort 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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGCohort 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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGCohort 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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGTROP2 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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGTKI
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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGAlbumin-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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGAlbumin-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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGalbumin-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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGHER2,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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGAR,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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGAR,AR antagonist +goserelin +docetaxel
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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGivonescimab + investigator-choice platinum doublet+
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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGiparomlimab + tuvonralimab
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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGcadonilimab
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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGCDK4/6 inhibitor+AI or fulvestrant
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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGalpelisib+fulvestrant
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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGPARP inhibitor
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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGenfortumab vedotin
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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGHER2, pyrotinib + 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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
DRUGvebecotutamab ±lenvatinib
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 is administered for 1 years, or until intolerable toxicity or withdrawal of consent. Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.
Sponsors
Peking Union Medical College
Peking University Hospital of Stomatology
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
The study employs a master-protocol platform design with the primary objective of identifying promising subgroups; new drug regimens may be added during the trial, while ineffective arms are closed based on interim monitoring. The trial consists of two stages. In Stage 1, each experimental arm uses a Bayesian Optimal Phase II (BOP2) design to assess whether the regimen shows sufficient efficacy to warrant further investigation. Arms demonstrating promising activity proceed to Stage 2（Simon two-stage design）.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | ORR at the end of Cycle 2 (each cycle is 21 days) | ORR rates for neoadjuvant and translational therapy in patients with locally advanced/recurrent and advanced oligometastatic salivary gland cancer and ORR rate of salvage therapy for locally advanced/recurrent or distantly metastatic salivary gland carcinoma with rapid progression that cannot tolerate or refuses surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MPR; | MPR rate at the end of surgical treatment | MPR rates in patients who received neoadjuvant and translational therapy and then underwent surgery |
| R0 resection rate; | R0 resection rate at the end of surgical treatment | R0 resection rate in patients who received neoadjuvant and translational therapy and then underwent surgery |
| Facial nerve protection rate | Facial nerve protection rate at the end of surgical treatment | Facial nerve protection rate in patients who received neoadjuvant and translational therapy and then underwent surgery |
| DFS | DFS rates at 3-year | 3-year DFS rates for patients who underwent surgery |
| PFS; | PFS Rate at 2-Year | 2-Year PFS Rate for Patients Receiving Rescue Therapy |
| OS | OS rate at 5-year | OS for all patients |
Countries
China
Contacts
CONTACTfei Ma
PRINCIPAL_INVESTIGATORJie Zhang
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology
Outcome results
None listed