Trastuzumab Emtansine for Salivary Gland Cancer

Recruiting at 123 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

Trial Summary

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.

What data supports the effectiveness of the drug Trastuzumab Emtansine for Salivary Gland Cancer?

Research shows that Trastuzumab Emtansine (T-DM1) has been effective in treating HER2-positive salivary gland tumors, with cases reporting excellent responses and partial remissions. It is used as a second-line treatment after progression on other therapies, indicating its potential benefit for patients with this type of cancer. ^{1 2 3 4 5}

Is trastuzumab emtansine generally safe for humans?

Trastuzumab emtansine (T-DM1) has been studied for safety in patients with HER2-positive breast cancer, showing manageable safety profiles. However, it can cause side effects like decreased platelet count and liver issues, and older age and male gender may increase the risk of serious side effects. ^{6 7 8 9 10}

How is the drug Trastuzumab Emtansine unique for treating salivary gland cancer?

Trastuzumab Emtansine (T-DM1) is unique because it combines trastuzumab, which targets the HER2 protein often overexpressed in aggressive salivary gland cancers, with emtansine, a drug that helps kill cancer cells. This combination allows it to specifically target and treat HER2-positive salivary gland tumors, offering a novel approach compared to traditional chemotherapy. ^{1 2 3 5 10}

What is the purpose of this trial?

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.

Research Team

Alan L Ho

Principal Investigator

NRG Oncology

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Role of ado-trastuzumab emtansine (T-DM1) in HER2 positive salivary gland tumour with brain metastasis. [2022]

2. England 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Metastatic HER-2-positive salivary gland carcinoma treated with trastuzumab and a taxane: a series of six patients. [2017]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Second-Line Treatment of HER2-Positive Salivary Gland Tumor: Ado-Trastuzumab Emtansine (T-DM1) after Progression on Trastuzumab. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Metastatic Parotid Gland Carcinoma With ERBB2 Amplification With Complete Response to Fam-Trastuzumab Deruxtecan. [2022]

6. England 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. [2023]

7. England 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. [2022]

8. Australia pubmed.ncbi.nlm.nih.gov

Adverse Event Profile Differences between Trastuzumab Emtansine and Trastuzumab Deruxtecan: A Real-world, Pharmacovigilance Study. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Acute skin radiation toxicity seen with concurrent T-DM1: A single institutional report of 35 patients. [2023]

10. England 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. [2020]