Trastuzumab Emtansine for Salivary Gland Cancer

Recruiting at 146 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NRG Oncology

Must not be taking: Anthracyclines

Disqualifiers: Unstable angina, Myocardial infarction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: Up to 18 weeks

146 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for HER2-positive salivary gland cancer that is recurrent, metastatic (spread to other parts of the body), or cannot be surgically removed. It compares the usual chemotherapy with docetaxel and trastuzumab to newer drugs like trastuzumab emtansine (Kadcyla) and trastuzumab deruxtecan. These new drugs target HER2 receptors on cancer cells, potentially improving treatment outcomes by delivering chemotherapy directly to the cancer cells. People with HER2-positive salivary gland cancer that has spread or returned, and who cannot have surgery, might be a good fit for this trial. As a Phase 2 trial, this research focuses on measuring how well the treatment works in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get specific guidance based on your situation.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that trastuzumab emtansine is generally safe and well-tolerated. In studies with patients who have aggressive salivary gland cancers, it proved effective and caused fewer severe side effects compared to other treatments. Specifically, 46.4% of patients experienced serious side effects, while 90.9% did with another treatment.

For trastuzumab deruxtecan, research indicates it can help control disease in patients with HER2-expressing cancers. However, 40.8% of patients experienced severe side effects, and about 10.5% developed a type of lung disease related to the drug.

Both treatments have been tested in patients with various types of cancer, demonstrating effectiveness but also some side effects. Anyone considering joining a trial should understand these potential risks and discuss them with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for salivary gland cancer because they offer new ways to target and treat the disease. Trastuzumab emtansine is unique because it combines trastuzumab, which targets HER2-positive cancer cells, with a chemotherapy agent that is delivered directly to the cancer cells, potentially increasing effectiveness and reducing side effects. Trastuzumab deruxtecan works similarly but is designed to be even more potent, providing another promising option. These treatments differ from the standard chemotherapy options by specifically targeting cancer cells, which may lead to better outcomes and fewer side effects for patients.

What evidence suggests that this trial's treatments could be effective for salivary gland cancer?

Research has shown that trastuzumab emtansine (T-DM1), which participants in this trial may receive, can effectively treat HER2-positive salivary gland cancer. Studies have found that T-DM1 works well and is safer than traditional chemotherapy, particularly for advanced cancer. For patients with HER2-amplified salivary gland tumors, T-DM1 has shown promising results. Additionally, the combination of docetaxel with trastuzumab, another treatment option in this trial, has a high success rate of 67-70% and can help control the cancer for about 8-9 months. These findings suggest that both T-DM1 and the docetaxel-trastuzumab combination could be effective treatment options for certain types of salivary gland cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Alan L Ho

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

Adults with HER2-positive salivary gland cancer that's recurrent, metastatic, or can't be surgically removed. Must have adequate organ function and agree to use effective contraception. Excludes those who've had systemic therapy for this cancer stage, certain severe health conditions, active infections requiring IV antibiotics, specific heart diseases, or untreated brain metastases.

Inclusion Criteria

Study-specific informed consent prior to study entry

AST and ALT =< 1.5 x institutional ULN

Patients with chronic HBV infection must have undetectable viral load

Exclusion Criteria

History of allergic reactions to specific compounds

I have been treated with anthracyclines before.

I have a lung condition involving scarring or fibrosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive assigned treatment (docetaxel plus trastuzumab, trastuzumab emtansine, or trastuzumab deruxtecan) every 21 days in cycles, with imaging and blood sample collection throughout the trial

Up to 18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 3 months for 2 years, then every 6 months for 3 years, then annually

Crossover Treatment (optional)

Participants may cross over to an alternative treatment arm upon disease progression

Variable

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Trastuzumab
• Trastuzumab Emtansine

Trial Overview

The trial is testing ado-trastuzumab emtansine (a targeted antibody linked to chemo) against the usual treatment of docetaxel plus trastuzumab in shrinking tumors. It aims to see if this new approach is more effective for patients with advanced HER2-positive salivary gland cancer.

How Is the Trial Designed?

Group I: Arm III (trastuzumab deruxtecan) Experimental Treatment 7 Interventions

Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan or MRI and ECHO or MUGA scan throughout the trial. Patients may also undergo blood sample collection and during screening and on study, as well as a biopsy during screening.

Group II: Arm II (trastuzumab emtansine) Experimental Treatment 6 Interventions

Patients receive trastuzumab emtansine IV over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients on Arm II (T-DM1) can cross over to Arm I (TH) after first progression. Patients undergo a CT scan or MRI throughout the trial. Patients may also undergo blood sample collection and during screening and on study, as well as a biopsy during screening.

Group III: Arm I (docetaxel, trastuzumab) Active Control 7 Interventions

Patients receive docetaxel IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive trastuzumab IV over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients on Arm I (TH) can cross over to Arm II (T-DM1) after first progression. Patients undergo a CT scan or MRI throughout the trial. Patients may also undergo blood sample collection and during screening and on study, as well as a biopsy during screening.

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a comparison of the safety profiles of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) using data from 3723 and 2045 adverse event reports respectively, T-DXd was associated with higher rates of fatal outcomes in the hematologic and respiratory systems, while T-DM1 had more severe outcomes in the hepatobiliary system.

Both drugs showed distinct adverse event patterns, with T-DM1 linked to nervous and musculoskeletal issues, and T-DXd associated with respiratory and gastrointestinal problems, highlighting the need for careful monitoring of specific risks in patients, especially those over 65 or on certain drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Event Profile Differences between Trastuzumab Emtansine and Trastuzumab Deruxtecan: A Real-world, Pharmacovigilance Study. Liu, F., Yin, G., Xue, S., et al.[2023]

Ado-trastuzumab emtansine (T-DM1), a targeted therapy combining trastuzumab and a cytotoxic drug, showed excellent efficacy in treating a patient with HER2-positive parotid gland adenocarcinoma with brain metastasis.

This case suggests that targeting the HER2 pathway with T-DM1 could be a promising systemic chemotherapy option for patients with aggressive salivary gland carcinomas, potentially improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of ado-trastuzumab emtansine (T-DM1) in HER2 positive salivary gland tumour with brain metastasis. Dhamne, N., Koyyala, VPB., Chougule, S., et al.[2022]

In the DESTINY-Breast03 trial, trastuzumab deruxtecan (T-DXd) demonstrated superior progression-free survival and overall survival compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer, while maintaining quality of life (QoL) throughout treatment.

Patients receiving T-DXd experienced a median time to first hospitalization that was three times longer than those on T-DM1, indicating better overall health management and fewer hospital visits during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Curigliano, G., Dunton, K., Rosenlund, M., et al.[2023]

A 79-year-old male patient with HER2-positive salivary duct cancer showed an excellent response to second-line treatment with T-DM1 after initially progressing on trastuzumab plus paclitaxel, indicating T-DM1's potential efficacy in this rare cancer.

The treatment resulted in significant tumor reduction with low toxicity, suggesting that maintaining HER2 blockage may be crucial for managing salivary duct cancer, especially in cases where standard treatments have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-Line Treatment of HER2-Positive Salivary Gland Tumor: Ado-Trastuzumab Emtansine (T-DM1) after Progression on Trastuzumab. Corrêa, TS., Matos, GDR., Segura, M., et al.[2022]

In a phase Ib/IIa study involving patients with HER2-positive metastatic breast cancer (MBC) and locally advanced breast cancer (LABC), the combination of trastuzumab emtansine (T-DM1) with docetaxel showed high efficacy, achieving an 80% objective response rate in MBC and a 60.3% pathologic complete response rate in LABC.

Despite the promising efficacy, nearly half of the patients experienced adverse events (AEs) that required dose modifications, with neutropenia being the most common severe AE, affecting 72% of MBC patients and 29% of LABC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine (T-DM1) plus docetaxel with or without pertuzumab in patients with HER2-positive locally advanced or metastatic breast cancer: results from a phase Ib/IIa study. Martin, M., Fumoleau, P., Dewar, JA., et al.[2022]

In a study of 35 HER2+ breast cancer patients receiving trastuzumab emtansine (T-DM1) with concurrent radiotherapy, a significant number experienced skin toxicity, with 22 patients reporting grade 2 or higher toxicity.

Three patients experienced grade 3 skin toxicities, highlighting the need for careful monitoring of skin reactions in patients undergoing this combined treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute skin radiation toxicity seen with concurrent T-DM1: A single institutional report of 35 patients. Dastgheyb, SS., Kim, K., Doucette, A., et al.[2023]

The KAMILLA study, involving 2002 patients with HER2-positive advanced breast cancer, demonstrated that trastuzumab emtansine (T-DM1) is a safe and tolerable treatment, with 93% of patients experiencing adverse events, primarily mild to moderate in severity.

The study reported a median progression-free survival of 6.9 months and a median overall survival of 27.2 months, indicating that T-DM1 is an effective option for patients who have previously undergone multiple lines of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive advanced breast cancer: Primary results from the KAMILLA study cohort 1. Montemurro, F., Ellis, P., Anton, A., et al.[2020]

In a study of 13 patients with recurrent or metastatic HER2-positive salivary duct carcinoma, the combination treatment of docetaxel, trastuzumab, and pertuzumab (DTP) resulted in a 58% objective response rate, indicating that this regimen is effective as a first-line therapy.

Following progression, the second-line treatment with ado-trastuzumab emtansine (T-DM1) also showed promising results, with a 57% response rate, and the overall survival after starting DTP was a median of 42 months, suggesting a favorable long-term outcome with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case series of docetaxel, trastuzumab, and pertuzumab (DTP) as first line anti-HER2 therapy and ado-trastuzumab emtansine (T-DM1) as second line for recurrent or metastatic HER2-positive salivary duct carcinoma. Uijen, MJM., Lassche, G., van Engen-van Grunsven, ACH., et al.[2022]

In a study of six patients with metastatic salivary gland carcinoma treated with trastuzumab and a taxane, the therapy was well tolerated and resulted in five partial responses and a median progression-free survival of 10.8 months, indicating its efficacy.

One patient achieved a complete and durable remission, and trastuzumab showed greater activity than androgen deprivation therapy when both HER-2 and androgen receptors were co-expressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic HER-2-positive salivary gland carcinoma treated with trastuzumab and a taxane: a series of six patients. De Block, K., Vander Poorten, V., Dormaar, T., et al.[2017]

Fam-trastuzumab deruxtecan has shown a complete response in a 67-year-old man with HER2-positive metastatic parotid gland carcinoma after previous treatments failed, indicating its potential efficacy in this type of cancer.

This novel antibody-drug conjugate appears to be well-tolerated and effective in patients with HER2-positive salivary gland carcinoma, suggesting it could be a promising treatment option that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic Parotid Gland Carcinoma With ERBB2 Amplification With Complete Response to Fam-Trastuzumab Deruxtecan. Shukla, ND., Chiang, RS., Colevas, AD.[2022]

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