Testing the Use of Ado-Trastuzumab Emtansine Compared to the Usual Treatment (Chemotherapy With Docetaxel Plus Trastuzumab) or Trastuzumab Deruxtecan for Recurrent, Metastatic, or Unresectable HER2-Expressing Salivary Gland Cancers

Recruiting now · Phase 2

Conditions studied: Metastatic Salivary Gland Carcinoma, Recurrent Salivary Gland Carcinoma, Stage III Major Salivary Gland Cancer AJCC v8, Stage IV Major Salivary Gland Cancer AJCC v8, Unresectable Salivary Gland Carcinoma

In brief

This phase II trial compares the effect of usual treatment of docetaxel chemotherapy plus trastuzumab, to ado-emtansine (T-DM1) in patients with HER2-postive salivary gland cancer that has come back (recurrent), that has spread from where it first started (primary site) to other places in the body, or cannot be removed by surgery (unresectable). This trial is also testing how well trastuzumab deruxtecan works in treating patients with HER2-low recurrent or metastatic salivary gland cancer. Trastuzumab is a form of targeted therapy because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by body's immune system. Trastuzumab emtansine contains trastuzumab, linked to a chemotherapy drug called emtansine. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers emtansine to kill them. Trastuzumab deruxtecan is a monoclonal antibody called traztuzumab, linked to a chemotherapy drug called deruxtecan. Trastuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors and delivers deruxtecan to kill them. Docetaxel is in a class of medications called taxanes. It stops cancer cells from growing and dividing and may kill them. Trastuzumab emtansine may work better compared to usual treatment of chemotherapy with docetaxel and trastuzumab or trastuzumab deruxtecan in treating patients with recurrent, metastatic or unresectable salivary gland cancer.

Key facts

Study ID

NCT05408845

Run by

NRG Oncology

People needed

146

Starts

2023-03-03

Expected to finish

2028-07-31

Last updated by the study team

2026-06-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Pathologically (histologically or cytologically) proven diagnosis of HER2-positive OR HER2-low expressing recurrent/metastatic salivary gland cancer (SGC)
• HER2-positive cohort:
• Note: The majority of HER2-positive SGCs are salivary duct carcinoma (SDCs), but to a lesser extent, other SGC subtypes can be HER2-positive (e.g., adenocarcinomas, mucoepidermoid carcinomas, etc.) and are eligible to be included on the study. Additionally, pathologists may sign out SDCs under other descriptors (e.g., ex-pleomorphic adenoma, adenocarcinoma), and these would be eligible if they are HER2-positive.
• Note: HER2 evaluation based on local site immunohistochemistry (IHC), fluorescent in-situ hybridization (FISH), or local/commercial next-generation sequencing (NGS) is required. Any one of the following criteria observed in a primary tumor or metastasis would meet the study definition for "HER2-positive":
• Immunohistochemistry (IHC) (3+) per the College of American Pathologists (CAP) breast cancer guidelines
• Gene amplification by FISH (HER2/CEP17 ratio >= 2.0)
• Gene amplification by NGS (fold change >= 2)
• HER2-low expressing cohort:
• Note: Local HER2 evaluation by immunohistochemistry (IHC) or fluorescent in-situ hybridization (FISH) is required. Any one of the following criteria observed in a primary tumor or metastasis would meet the study definition for "HER2-low":
• IHC 1+ per the College of American Pathologists (CAP) breast cancer guidelines
• IHC 2+ without evidence of amplification by FISH
• Patients with unresectable disease who are not candidates for curative surgery or radiation OR recurrent OR metastatic disease that is evident on radiologic imaging
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
• HER2-positive cohort: Measurable or non-measurable disease by the RECIST v1.1 criteria. HER2-low expressing cohort: Measurable disease by the RECIST v1.1 criteria
• History/physical examination within 30 days prior to registration
• The following imaging within 60 days prior to registration:
• CT or MRI of the neck (diagnostic quality with contrast, unless contraindicated) AND
• CT scan of the chest (diagnostic quality with contrast, unless contraindicated) AND
• If clinically indicated, CT or MRI of the abdomen and pelvis (diagnostic quality with contrast, unless contraindicated)
• Age >= 18
• Left ventricular ejection fraction (LVEF) >= 50% assessed by echocardiogram or multigated acquisition (MUGA) scan within 30 days prior to registration
• Zubrod (Eastern Cooperative Oncology Group [ECOG]) Performance Status of 0-2 within 14 days prior to registration
• Absolute neutrophil count (ANC) >= 1,500 cells/mm\^3 (within 14 days prior to registration)
• Platelets >= 100,000 cells/mm\^3 (within 14 days prior to registration)

You may not qualify if…

• HER2-positive cohort: Prior systemic therapy for the study cancer in the unresectable or recurrent and/or metastatic disease setting
• Note: Prior chemotherapy for a different cancer is allowed; prior androgen receptor targeted therapy in any setting is allowed; prior systemic therapy, including HER2-directed therapies given as neoadjuvant therapy, adjuvant therapy, and/or concurrently with radiation is allowed
• HER2-low expressing cohort: HER2 directed therapy for unresectable or recurrent or metastatic disease is not allowed
• Severe, active co-morbidity defined as follows:
• Unstable angina requiring hospitalization in the last 6 months
• Myocardial infarction within the last 6 months
• New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
• Persistent grade 3-4 (CTCAE version 5.0) electrolyte abnormalities that cannot be reversed despite replacement as indicated by repeat testing
• Patient must not have an active infection requiring IV antibiotics, antivirals, or antifungals
• HER2-positive cohort only: >= grade 3 peripheral neuropathy
• Interstitial lung disease or pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on chest CT scan
• Any hemorrhage or bleeding event grade >= 3 within 28 days prior to registration
• History of allergic reactions to compounds of similar chemical or biologic composition to: HER2-positive cohort: ado-trastuzumab emtansine, trastuzumab, and/or docetaxel (or any of their excipients). HER2-low expressing cohort: DS-8201a (trastuzumab deruxtecan), trastuzumab
• History of exposure to the following cumulative doses of anthracyclines:
• Doxorubicin or liposomal doxorubicin > 500 mg/m\^2
• Epirubicin > 900 mg/m\^2
• Mitoxantrone > 120 mg/m\^2
• Note: If another anthracycline, or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of doxorubicin 500 mg/m\^2
• HER2-low expressing cohort only: Receipt of live, attenuated vaccine (messenger ribonucleic acid [mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of DS-8201a (trastuzumab deruxtecan)
• Pregnancy and individuals unwilling to discontinue nursing

Where it is running

• Miami Cancer Institute — Miami, Florida, United States (enrolling)
• Emory University Hospital Midtown — Atlanta, Georgia, United States (enrolling)
• UCHealth Highlands Ranch Hospital — Highlands Ranch, Colorado, United States (enrolling)
• Kaiser Permanente Fresno Orchard Plaza — Fresno, California, United States (enrolling)
• Kaiser Permanente-Fresno — Fresno, California, United States (enrolling)
• Kaiser Permanente Dublin — Dublin, California, United States (enrolling)
• Kaiser Permanente-Fremont — Fremont, California, United States (enrolling)
• Kaiser Permanente-Modesto — Modesto, California, United States (enrolling)
• Kaiser Permanente-Oakland — Oakland, California, United States (enrolling)
• Stanford Cancer Institute Palo Alto — Palo Alto, California, United States (enrolling)
• Kaiser Permanente-Roseville — Roseville, California, United States (enrolling)
• Kaiser Permanente Downtown Commons — Sacramento, California, United States (enrolling)
• Kaiser Permanente-South Sacramento — Sacramento, California, United States (enrolling)
• Kaiser Permanente-San Francisco — San Francisco, California, United States (enrolling)
• Kaiser Permanente- Modesto MOB II — Modesto, California, United States (enrolling)
• Kaiser Permanente-Santa Teresa-San Jose — San Jose, California, United States (enrolling)
• Kaiser Permanente San Leandro — San Leandro, California, United States (enrolling)
• Kaiser San Rafael-Gallinas — San Rafael, California, United States (enrolling)
• Kaiser Permanente Medical Center - Santa Clara — Santa Clara, California, United States (enrolling)
• Kaiser Permanente-Santa Rosa — Santa Rosa, California, United States (enrolling)
• Kaiser Permanente-South San Francisco — South San Francisco, California, United States (enrolling)
• Kaiser Permanente-Vallejo — Vallejo, California, United States (enrolling)
• Kaiser Permanente-Walnut Creek — Walnut Creek, California, United States (enrolling)
• UCHealth University of Colorado Hospital — Aurora, Colorado, United States (enrolling)
• Kaiser Permanente Moanalua Medical Center — Honolulu, Hawaii, United States (enrolling)

Full record on ClinicalTrials.gov

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