T-DM1 for Breast Cancer

Recruiting at 87 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Pregnant, Alcohol, Liver disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 28

Duration: 51 weeks

512 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA has not approved this drug for use patients undergoing adjuvant treatment for HER2+ breast cancer. Trastuzumab emtansine (T-DM1) is a drug that may stop cancer cells from growing. This drug has been used in other research studies and information from those other research studies suggests that this drug may help to prevent the recurrence of breast cancer in this research study. The use of T-DM1 in this research study is experimental, which means it is not approved by any regulatory authority for the adjuvant treatment of HER2-positive breast cancer. However, it FDA-approved for metastatic HER2-positive breast cancer. T-DM1 has caused cancer cells to die in laboratory studies. In preclinical studies, this drug has prevented or slowed the growth of breast cancer. The breast cancer treatments (paclitaxel and Trastuzumab) used in this study are considered part of standard-of-care regimens in early breast cancer. A standard treatment means that this is a treatment that would be accepted by the majority of the medical community as a suitable treatment for your type of breast cancer. In this research study, the investigators are looking to see if the study drug T-DM1 will have less side effects than traditional HER2-positive breast cancer treatment of trastuzumab and paclitaxel. The investigators are also hoping to learn about the long term benefits and disease-free survival of participants who take the study drug T-DM1 in comparison to those participants to take the combination of trastuzumab and paclitaxel.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop any investigational drugs at least 2 weeks before joining. You cannot use potent CYP3A4 inhibitors during the study.

What data supports the effectiveness of the drug T-DM1 for breast cancer?

T-DM1 has been shown to be effective for HER2-positive metastatic breast cancer, as it was approved based on a large trial that demonstrated its benefits over other treatments. It combines targeted therapy with chemotherapy to improve outcomes while reducing side effects. ^{1 2 3 4 5}

What is the safety profile of T-DM1 for breast cancer treatment?

T-DM1, used for HER2-positive breast cancer, has been studied for safety in several trials. Common side effects include skin toxicity and lacrimal drainage system issues, but it generally has a favorable safety profile compared to other treatments like capecitabine plus lapatinib. ^{1 5 6 7 8}

What makes the drug T-DM1 unique for treating HER2-positive breast cancer?

T-DM1 is unique because it combines trastuzumab, which targets cancer cells, with a powerful chemotherapy drug, emtansine, to deliver treatment directly to the cancer cells, reducing side effects on healthy cells. This targeted approach is particularly effective for HER2-positive breast cancer, even in cases where other treatments have failed. ^{2 3 7 9 10}

Research Team

Sara Tolaney, MD, MPH

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for individuals with HER2-positive Stage I breast cancer, who have had recent surgery and may have started hormonal therapy. They must not be pregnant or breastfeeding, free from certain other cancers for 5 years, without active infections or liver disease, and agree to use effective contraception.

Inclusion Criteria

All margins should be clear of invasive cancer or DCIS

Must have discontinued any investigational drug at least 2 weeks prior to participation

I have had my ovaries removed to prevent cancer.

Exclusion Criteria

Excessive alcohol intake (more than 3 alcoholic beverages per day)

I have had chemotherapy within the last 5 years.

I have an active liver condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either T-DM1 every three weeks for 51 weeks or Paclitaxel and Trastuzumab weekly for 12 weeks followed by Trastuzumab every three weeks for 39 weeks

51 weeks

17 visits (in-person) for T-DM1 group, 25 visits (in-person) for Paclitaxel/Trastuzumab group

Radiation

Participants who undergo lumpectomy receive breast radiation therapy; those with mastectomy may receive chest wall and lymph node radiation

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment with regular visits every 6 months for 3 years, then annually for 2 years

5 years

10 visits (in-person)

Treatment Details

Interventions

• Paclitaxel
• Trastuzumab
• Trastuzumab emtansine

Trial Overview The ATEMPT trial is testing the effectiveness of T-DM1 (an investigational drug) against the standard treatment combination of paclitaxel and trastuzumab in preventing breast cancer recurrence. It's a Phase II study comparing side effects and long-term benefits.

Participant Groups

Group I: Paclitaxel + Trastuzumab Active Control 2 Interventions

paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments

Group II: Trastuzumab emtansine (T-DM1) Active Control 1 Intervention

T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks

Trastuzumab emtansine is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as Kadcyla for:

• HER2-positive metastatic breast cancer
• HER2-positive early breast cancer with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment

Approved in European Union as Kadcyla for:

• HER2-positive metastatic breast cancer
• HER2-positive early breast cancer with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment

Approved in United Kingdom as Kadcyla for:

• HER2-positive metastatic breast cancer
• HER2-positive early breast cancer with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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]

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 a study of 128 patients with advanced HER2+ breast cancer treated with ado-trastuzumab emtansine (T-DM1), the median progression-free survival was 8.7 months and overall survival was 20.4 months, indicating its efficacy in a real-world setting.

The safety profile of T-DM1 was consistent with existing literature, but the study noted higher rates of peripheral neuropathy (21.9%) and liver toxicity (19.5%), which are important considerations for its use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of T-DM1 in patients with advanced HER2-positive breast cancer The Royal Marsden experience. Battisti, NML., Rogerson, F., Lee, K., et al.[2021]

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 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]

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]

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]

Trastuzumab emtansine (T-DM1) demonstrated superior inhibitory effects on HER-2-positive colon cancer cells with KRAS/BRAF mutations compared to other treatments like cetuximab and trastuzumab, suggesting its potential as an effective therapy for this challenging cancer type.

The combination of T-DM1 with metformin enhanced the drug's efficacy by increasing caveolin-1 expression, which improved T-DM1 uptake and led to significant tumor growth inhibition in a xenograft mouse model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of trastuzumab emtansine in HER-2-positive and KRAS/BRAF-mutated colon cancer cells. Chung, YC., Chiu, HH., Wei, WC., et al.[2020]

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. 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]

3. China pubmed.ncbi.nlm.nih.gov

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

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

Safety and efficacy of T-DM1 in patients with advanced HER2-positive breast cancer The Royal Marsden experience. [2021]

5. England pubmed.ncbi.nlm.nih.gov

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

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. Singapore pubmed.ncbi.nlm.nih.gov

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

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

Application of trastuzumab emtansine in HER-2-positive and KRAS/BRAF-mutated colon cancer cells. [2020]

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

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