A multicenter, single arm study of trastuzumab emtansine (T-DM1) in HER2 positive locally advanced or metastatic breast cancer patients who have received prior anti-HER2 and chemotherapy-based treatment

Phase 3

Completed

• Conditions: breast cancer; HER2 positive locally advanced or metastatic breast cancer; 10006291

• Registration Number: NL-OMON39697
• Lead Sponsor: Roche Nederland B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 30

Inclusion Criteria

1. HER2-positive disease determined locally i.e., IHC 3 + and/or gene-amplified by in-situ hybridization (ISH) as per institutional practice, (however, both tests should be performed wherever possible and only one positive result is required for eligibility)
2. Histologically or cytologically confirmed invasive BC
3. Prior treatment for BC in the advanced/metastatic, unresectable locally advanced or metastatic setting must include an anti-HER2 agent and chemotherapy in combination or sequential administration (complementary hormonal therapy is allowed)
4. Documented progression of incurable, unresectable, locally advanced, or mBC, defined by the investigator: progression must occur during or after most recent treatment for locally advanced/mBC or within 6 months after completing adjuvant therapy
5. Measurable and/or non-measurable disease
6. Signed written informed consent approved by the institution*s independent Ethics Committee (EC)
7. Age >= 18 years
8. Left ventricular ejection fraction >= 50% by either ECHO or MUGA
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
10. Adequate organ function
11. For women of childbearing potential and men with partners of childbearing potential agreement by the patient and/or partner to use a highly effective non-hormonal form of contraception.
12. Negative serum pregnancy test for women of childbearing potential and for all women not meeting the definition of postmenopausal, and who have not undergone surgical
sterilization with a hysterectomy and/or bilateral oophorectomy. For all other women, documentation must be present in medical history confirming that the patient is not of childbearing potential.

Exclusion Criteria

1. History of treatment with trastuzumab emtansine;2. Prior enrolment into a clinical study containing trastuzumab emtansine regardless of having received trastuzumab emtansine or not;3. Peripheral neuropathy of Grade >= 3 per NCI CTCAE Version 4.0;4. History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed HER2-positive breast cancer, or cancers with a similar curative outcome as those mentioned above;5. History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to first study treatment except hormone therapy, which can be given up to 7 days prior to first study treatment; recovery of treatment-related toxicity consistent with other eligibility criteria;6. History of exposure to the following cumulative doses of anthracyclines:;• Doxorubicin or liposomal doxorubicin > 500 mg/m2;• Epirubicin > 900 mg/m2;• Mitoxantrone >120 mg/m2;• If another anthracycline, or more than one anthracycline, has been used, the cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin.;7. History of radiation therapy within 14 days of first study treatment. The patient must have recovered from any resulting acute toxicity (to Grade <= 1) prior to first study treatment.;8. Metastatic CNS disease only;9. Brain metastases which are symptomatic. NOTE: A 14 days window after end of radiotherapy must be observed. Patient must not be receiving steroids to control symptoms.;10. History of a decrease in LVEF to < 40% or symptomatic CHF with previous trastuzumab treatment;11. History of symptomatic congestive heart failure (CHF; New York Heart Association [NYHA] Classes II*IV) or serious cardiac arrhythmia requiring treatment;12. History of myocardial infarction or unstable angina within 6 months of first study treatment;13. Current dyspnea at rest due to complications of advanced malignancy or requirement for continuous oxygen therapy;14. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease);15. Pregnancy or lactation;16. Currently known active infection with HIV, hepatitis B virus, or hepatitis C virus;17. History of intolerance (such as Grade 3*4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any component of the product. ;18. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol throughout

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of this study is to evaluate the safety and tolerability<br /><br>of trastuzumab emtansine.<br /><br>The safety outcome measures for this study are as follows:<br /><br>• Incidence, nature and severity by National Cancer Institute (NCI) common<br /><br>terminology criteria for adverse events (CTCA version 4.0 of AEs and SAEs<br /><br>• Incidence of congestive heart failure (CHF)<br /><br>• Left ventricular ejection fraction (LVEF) decrease over the course of the<br /><br>study<br /><br>• Laboratory test abnormalities<br /><br>• Premature withdrawal from study and study medication<br /><br>• Exposure to study medication</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>A secondary objective of this study is to evaluate efficacy of trastuzumab<br /><br>emtansine treatment.<br /><br>The efficacy outcome measures for this study are as follows:<br /><br>• Progression free survival (PFS)<br /><br>• Overall survival (OS)<br /><br>• Overall response rate (ORR) = partial response (PR) + complete response (CR)<br /><br>• Clinical benefit rate (CBR)<br /><br>• Duration of response (DoR)<br /><br>• Time To Response (TTR)<br /><br>The pharmacoeconomics outcomes defined in Section 2.3 will be measured.<br /><br>• To evaluate the resource expenditures, while on study treatment, due to<br /><br>hospitalizations that are not study-defined evaluations. The number of hospital<br /><br>visits, number of days admitted, and type of visits (emergency department<br /><br>versus inpatient care) will be recorded</p><br>