Trial Summary
What is the purpose of this trial?This trial is testing a special drug called T-DM1 combined with regular cancer treatments in patients with HER2-positive salivary gland cancer. The drug targets cancer cells specifically and delivers chemotherapy directly to them. The goal is to see if this combination is safe and effective in preventing cancer recurrence. T-DM1 has shown effectiveness in treating HER2-positive cancers, including breast and salivary gland cancers, by targeting cancer cells and delivering chemotherapy directly to them.
What safety data is available for T-DM1 treatment?The safety profile of T-DM1 (Kadcyla) has been primarily studied in HER2-positive metastatic breast cancer. The EMILIA trial showed differences in safety between T-DM1 and capecitabine plus lapatinib, with specific adverse events noted. T-DM1 has been associated with lacrimal drainage system stenosis and skin toxicity when used with radiotherapy. These findings highlight the need for careful monitoring of adverse events during treatment.235910
Is the drug T-DM1 a promising treatment for salivary gland cancer?Yes, T-DM1 is a promising drug for treating salivary gland cancer, especially in cases where the cancer is aggressive and HER2-positive. It has shown excellent results in treating similar types of cancer, like HER2-positive breast cancer, by targeting and blocking specific cancer pathways. This makes it a valuable option for patients with this type of cancer.12489
What data supports the idea that T-DM1 + Chemoradiation for Salivary Gland Cancer is an effective treatment?The available research shows that T-DM1, also known as Kadcyla, has been effective in treating HER2-positive breast cancer, particularly in cases where the cancer has spread or is advanced. It combines a targeted approach with a powerful cancer-fighting drug, which has shown to improve outcomes for breast cancer patients. However, there is no specific data provided here about its effectiveness for salivary gland cancer. The research mainly focuses on breast cancer, so while T-DM1 has potential, more studies are needed to confirm its effectiveness for salivary gland cancer.24679
Do I have to stop taking my current medications for this trial?The trial protocol does not specify if you need to stop taking your current medications. However, since the trial involves chemoradiation and a new drug, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators or your doctor for specific guidance.
Eligibility Criteria
Adults with HER2-positive salivary gland cancer that can be surgically removed, and who haven't had prior HER2 therapy or chemotherapy/radiotherapy for head and neck cancer. They must have good organ function, not be pregnant or breastfeeding, willing to provide tissue and blood samples, and able to sign consent. Men must use effective contraception.Inclusion Criteria
I am 18 years old or older.
I am mostly self-sufficient and can carry out daily activities.
My salivary gland cancer is advanced but can be surgically removed.
My cancer is HER2 positive.
My heart's pumping ability is confirmed to be normal before starting treatment.
My cancer has a high level of HER2 according to a specific test.
My tumor shows a HER2 intensity of 2 or 3+.
My cancer has a specific HER2 or ERBB2 mutation.
Exclusion Criteria
I do not have any severe illnesses that would stop me from following the study's requirements.
I do not have any active or uncontrolled infections.
I have received radiation or chemotherapy for head and neck cancer.
My cancer is either at an early stage, very advanced, or cannot be removed by surgery.
I have received treatments specifically targeting HER2 in the past.
I have another cancer that is getting worse or needs treatment.
Treatment Details
The trial is testing the safety and effectiveness of Ado-trastuzumab emtansine (T-DM1) combined with standard chemoradiation in treating resectable HER2-positive salivary gland carcinomas. It also looks at T-DM1's impact on preventing cancer recurrence.
1Treatment groups
Experimental Treatment
Group I: Standard of Care + T-DM1 in HER2-Positive Salivary Gland CancerExperimental Treatment3 Interventions
Participants will undergo standard of care surgery followed by standard of care radiation and chemotherapy with the addition of T-DM1.
Study cycles are 21 days (3 weeks):
* Participants will be given the study treatment T-DM1 at a predetermined dose (3.6 mg/kg) intravenously once (1x) every 3 weeks for up to 52 weeks (or about 1 year).
* Participants will be given standard of care radiation and chemotherapy
* Radiation will be given on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, and Cycle 3 Day 1
* Chemotherapy (cisplatin 40 mg/m2 intravenously or carboplatin AUC 2 intravenously) will be given on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, and Cycle 3 Day 1
Participants will be followed for 3 years.
Ado-trastuzumab emtansine (T-DM1) is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Kadcyla for:
- HER2-positive, metastatic breast cancer
🇪🇺 Approved in European Union as Kadcyla for:
- HER2-positive, metastatic breast cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
Memorial Sloan Kettering CommackCommack, NY
University of Washington Medical CenterSeattle, WA
Memorial Sloan Kettering Basking RidgeBasking Ridge, NJ
Memorial Sloan Kettering BergenMontvale, NJ
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Who is running the clinical trial?
Dana-Farber Cancer InstituteLead Sponsor
Genentech, Inc.Industry Sponsor
References
Trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. [2022]Trastuzumab emtansine (T-DM1), a novel drug developed for the treatment of HER2-positive breast cancer, is a human epidermal growth factor receptor (HER2) targeted antibody drug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine). It has been shown that, in preclinical studies, it has anti-tumor activity in trastuzumab refractory cancer cells. In this review, we aim to show the clinical data about trastuzumab-DM1 (T-DM1) therapy and to discuss the therapy advantages for the management of patients with HER2-positive breast cancer.
Ado-trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: latest evidence and clinical potential. [2022]In February 2013, ado-trastuzumab emtansine (T-DM1, Kadcyla®) received regulatory approval in the United States for treatment-refractory human epidermal growth factor receptor 2 (HER2) positive metastatic or locally advanced breast cancer based on results from EMILIA, a large phase III trial that compared standard of care lapatinib plus capecitabine to T-DM1. Several other studies have been reported in the metastatic setting and multiple trials are ongoing or planned in the neoadjuvant, adjuvant and advanced disease settings. Here we provide an updated and comprehensive review of clinical trials evaluating T-DM1, discuss management of toxicity associated with this drug, propose potential mechanisms of resistance and offer practical considerations for the treating oncologist.
Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System. [2019]Trastuzumab emtansine (T-DM1, KADCYLA(®)) is an antibody-drug conjugate comprised of the cytotoxic agent DM1 and trastuzumab (HERCEPTIN(®)). The safety profile of T-DM1 in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane was investigated in the phase III EMILIA trial. The trial demonstrated clinically and statistically meaningful differences in the safety profile between T-DM1 and capecitabine plus lapatinib (CAP + LAP). The objective of this study was to estimate the costs of managing treatment-related grade ≥ 3 adverse events (AEs) that occurred in ≥ 2% of patients and grade 2 AEs that occurred in ≥ 5% of patients taking T-DM1 compared with patients taking CAP + LAP based on the EMILIA trial, from the perspective of Canadian public payers.
Treatment of HER2 positive advanced breast cancer with T-DM1: A review of the literature. [2022]Trastuzumab emtansine (T-DM1), a new agent developed for the treatment of HER2-positive breast cancer, is an antibody-drug conjugate with a complex compound obtained by the conjugation of trastuzumab, a stable thioether linker, and the potent cytotoxic drug maytansine-derivate(DM1), which inhibits cell division and induces cell death.
Lacrimal drainage system stenosis associated with Trastuzumab emtansine (Kadcyla®, T-DM1) administration: a case report. [2020]Trastuzumab emtansine (Kadcyla®, T-DM1) is an antibody-drug conjugate used to treat HER2 (human epidermal growth factor receptor 2) overexpressing metastatic breast cancer. In this report, we present the first case of lacrimal drainage system stenosis identified after T-DM1 administration, and its successful treatment with a topical steroid.
[Clinical research progress of T-DM1 in breast cancer]. [2021]Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) composed of trastuzumab, a linker, and a microtubule inhibitor. T-DM1 combines the highly effective targeting of antibody with the high anti-tumor activity of cytotoxic drugs, while reduces the off-target toxic side effects of cytotoxic drugs. T-DM1 has been applied in neoadjuvant therapy of HER2-positive breast cancer and rescue treatment of advanced breast cancer, greatly improves the prognosis of breast cancer patients. More and more clinical trials of T-DM1 for HER2 breast cancer and other solid tumors are ongoing, and more positive results are expected.
Real-world effectiveness of post-trastuzumab emtansine treatment in patients with HER2-positive, unresectable and/or metastatic breast cancer: a retrospective observational study (KBCSG-TR 1917). [2023]Trastuzumab emtansine (T-DM1) is a second-line standard therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Evidence regarding post-T-DM1 treatments is currently lacking. We evaluated the effectiveness of post-T-DM1 drug therapy in patients with HER2-positive, unresectable and/or metastatic breast cancer.
Role of ado-trastuzumab emtansine (T-DM1) in HER2 positive salivary gland tumour with brain metastasis. [2022]Malignant neoplasms of salivary gland neoplasms are rare and often involve the parotid gland. The primary treatment of these malignancies is surgery with or without adjuvant therapy. Chemotherapy or systemic therapy is indicated in recurrent or metastatic disease where surgery or radiotherapy is not possible. Salivary gland carcinomas, which are human epidermal growth factor receptor 2 (HER2) positive, show an aggressive behaviour with a poor prognosis. Targeting the HER2 pathway with drugs designed to block this pathway is an interesting novel therapy to treat salivary gland carcinomas. We report a case of a patient with HER 2-overexpressing parotid gland adenocarcinoma with brain metastasis, who was managed with ado-trastuzumab emtansine (T-DM1): a monoclonal antibody-cytotoxic drug conjugate that combines trastuzumab with the microtubule inhibitor, emtansine. The patient showed excellent response to the therapy. This case highlights the role of systemic chemotherapy with T-DM1 in HER2 positive salivary gland tumours that could be considered a part of the treatment regimen.
Biological Evaluation of Maytansinoid-Based Site-Specific Antibody-Drug Conjugate Produced by Fully Chemical Conjugation Approach: AJICAP®. [2022]Trastuzumab-emtansine (T-DM1, commercial name: Kadcyla) is well-known antibody-drug conjugate (ADC) and was first approved for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. This molecular format consisting of trastuzumab and maytansinoid payload (emtansine) is very simple, however, T-DM1 has wide heterogeneity due to non-specific conjugation, lowering its therapeutic index (TI).
Acute skin radiation toxicity seen with concurrent T-DM1: A single institutional report of 35 patients. [2023]Trastuzumab emtansine (T-DM1) is a novel therapeutic for HER2+ breast cancer patients with residual disease after neoadjuvant chemotherapy. Concurrent radiotherapy (RT) is offered to a subset of patients based on results from the KATHERINE trial which showed a favorable safety profile. With emerging therapies that necessitate concurrent RT, we must closely follow rates of skin toxicity. Our first 35 patients who underwent concurrent T-DM1 treatment with breast/chest wall (CW) ± nodal irradiation are reported. Most patients (22/35) had grade 2+ toxicity and 3 patients had grade 3 toxicities. We add our experience with radiation dermatitis and concurrent T-DM1 to contribute to existing reports.