T-DM1 + Chemoradiation for Salivary Gland Cancer

Recruiting at 11 trial locations

Overseen By Glenn J. Hanna, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: HER2 therapies

Disqualifiers: Stage I, IVC, Prior radiation, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 52 weeks

55 Participants Needed

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.

Will I have to stop taking my current medications?

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 T-DM1 for treating salivary gland cancer?

T-DM1, also known as Kadcyla, has shown effectiveness in treating HER2-positive breast cancer by targeting cancer cells and delivering a potent drug to kill them, which suggests potential for treating other cancers like salivary gland cancer. ^{1 2 3 4 5}

Is T-DM1 (Kadcyla) generally safe for humans?

T-DM1 (Kadcyla) has been used in treating HER2-positive breast cancer and has shown some side effects, such as skin toxicity and lacrimal drainage system stenosis (a blockage in the tear drainage system). However, it has a generally favorable safety profile when used with radiotherapy, though some patients may experience moderate to severe skin reactions. ^{1 2 6 7 8}

What makes the drug T-DM1 unique for treating salivary gland cancer?

T-DM1 is unique because it targets the HER2 protein, which is often overexpressed in aggressive salivary gland cancers, and combines a monoclonal antibody with a powerful cancer-killing agent, emtansine, to directly attack cancer cells. This targeted approach is novel for salivary gland cancer, which typically has limited treatment options beyond surgery. ^{1 2 3 9 10}

Research Team

Glenn J. Hanna, MD

Principal Investigator

Dana-Farber Cancer Institute

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

leukocytes ≥ 3,000/mcL

I am mostly self-sufficient and can carry out daily activities.

My salivary gland cancer is advanced but can be surgically removed.

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 had skin cancer or early-stage cervical/prostate cancer treated curatively, or any cancer in remission for 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive T-DM1 in combination with radiation and chemotherapy for up to 1 year

52 weeks

1 visit every 3 weeks for T-DM1 administration, multiple visits for radiation and chemotherapy

Maintenance

Participants receive maintenance T-DM1 alone for up to a year after surgery

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Treatment Details

Interventions

• Ado-trastuzumab emtansine (T-DM1)
• Standard of Care Chemotherapy
• Standard of Care Radiotherapy

Trial Overview 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.

Participant Groups

Group I: Standard of Care + T-DM1 in HER2-Positive Salivary Gland Cancer Experimental Treatment 3 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

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

Ado-trastuzumab emtansine (T-DM1) was approved in the U.S. for treating HER2 positive metastatic breast cancer based on the EMILIA phase III trial, which showed it was more effective than the standard treatment of lapatinib plus capecitabine.

Ongoing and planned trials are exploring T-DM1's use in various stages of breast cancer, and the review discusses its toxicity management and potential resistance mechanisms, highlighting its importance in current cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ado-trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: latest evidence and clinical potential. Peddi, PF., Hurvitz, SA.[2022]

The novel AJICAP® technology allows for site-specific conjugation of antibodies, resulting in a trastuzumab-maytansinoid ADC that has a higher maximum tolerated dose compared to the commercially available T-DM1, indicating an improved therapeutic index.

Initial safety studies in rats showed that the AJICAP-ADC demonstrated greater stability and tolerability than T-DM1, suggesting it could be a more effective treatment option for HER2-positive metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological Evaluation of Maytansinoid-Based Site-Specific Antibody-Drug Conjugate Produced by Fully Chemical Conjugation Approach: AJICAP®. Seki, T., Yamada, K., Ooba, Y., et al.[2022]

Trastuzumab emtansine (T-DM1) is an effective treatment for HER2-positive breast cancer, showing significant improvements in progression-free survival and overall survival in patients who have previously undergone anti-HER2 therapies, as demonstrated in phase III trials EMILIA and TR3RESA.

The safe dosing range for T-DM1 has been established at 3.6 mg/kg every 3 weeks, and it has a favorable safety and tolerability profile, making it a promising option for patients with advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of HER2 positive advanced breast cancer with T-DM1: A review of the literature. Martínez, MT., Pérez-Fidalgo, JA., Martín-Martorell, P., et al.[2022]

In a study of 128 female patients with HER2-positive metastatic breast cancer who previously received trastuzumab emtansine (T-DM1), the median progression-free survival (rwPFS) was 5.7 months, indicating some effectiveness of post-T-DM1 therapies.

Patients who continued anti-HER2 therapy after T-DM1 had a better median rwPFS of 6.3 months compared to 4.8 months for those who did not, suggesting that ongoing anti-HER2 treatment may provide additional benefits, although overall effectiveness remains limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Nakayama, T., Yoshinami, T., Yasojima, H., et al.[2023]

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that effectively targets HER2-positive breast cancer while minimizing off-target side effects, combining the benefits of targeted therapy with potent cytotoxic action.

T-DM1 has shown significant improvements in patient prognosis when used in neoadjuvant therapy and as a rescue treatment for advanced breast cancer, with ongoing clinical trials exploring its efficacy in other solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical research progress of T-DM1 in breast cancer]. Li, LX., Ma, F.[2021]

In the phase III EMILIA trial, trastuzumab emtansine (T-DM1) demonstrated a significantly better safety profile compared to capecitabine plus lapatinib (CAP + LAP) in treating HER2-positive metastatic breast cancer, leading to fewer severe treatment-related adverse events.

The management of adverse events resulted in lower costs for T-DM1 (CAD 3380) compared to CAP + LAP (CAD 6901), indicating that T-DM1 not only provides effective treatment but also offers substantial savings to the Canadian public health-care system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Piwko, C., Prady, C., Yunger, S., et al.[2019]

Trastuzumab emtansine (T-DM1) can cause lacrimal drainage system stenosis, leading to excessive tearing in patients, as seen in a case study of a 36-year-old woman with metastatic breast cancer.

The condition was successfully treated with a topical steroid (dexamethasone), demonstrating that while T-DM1 is effective for HER2-positive breast cancer, it can have side effects that are manageable with appropriate treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacrimal drainage system stenosis associated with Trastuzumab emtansine (Kadcyla®, T-DM1) administration: a case report. Kim, CY., Kim, N., Choung, HK., et al.[2020]

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]

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]

Trastuzumab emtansine (T-DM1) has demonstrated significant efficacy in treating HER2-positive metastatic breast cancer, showing improved progression-free and overall survival compared to standard treatments in the phase III EMILIA trial.

T-DM1 has a favorable safety profile and is being studied in ongoing trials to determine its effectiveness in earlier stages of HER2-positive breast cancer, indicating its potential for broader application in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. Boyraz, B., Sendur, MA., Aksoy, S., et al.[2022]

References

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

Ado-trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: latest evidence and clinical potential. [2022]

2. Singapore pubmed.ncbi.nlm.nih.gov

Biological Evaluation of Maytansinoid-Based Site-Specific Antibody-Drug Conjugate Produced by Fully Chemical Conjugation Approach: AJICAP®. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of HER2 positive advanced breast cancer with T-DM1: A review of the literature. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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]

5. China pubmed.ncbi.nlm.nih.gov

[Clinical research progress of T-DM1 in breast cancer]. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

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]

7. England pubmed.ncbi.nlm.nih.gov

Lacrimal drainage system stenosis associated with Trastuzumab emtansine (Kadcyla®, T-DM1) administration: a case report. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. [2022]