Clinical trial NCT06125834: Trastuzumab Emtansine (T-DM1) in HER2-positive Breast Cancer Patients With Progressive Disease After TKIs or HP Therapy
Official title: Trastuzumab Emtansine (T-DM1) Treatment in HER2-positive Breast Cancer Patients With Progressive Disease After TKIs or HP Therapy: a Multicenter, Single-arm, Phase II Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Breast Cancer
Objective Response Rate
Trastuzumab Emtansine
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2023-11-09
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn about the efficacy and safety of trastuzumab emtansine (T-DM1) in the treatment of patients with advanced HER2-positive breast cancer after TKIs or HP therapy. The main questions it aims to answer are:

* The objective response rate of patients receiving T-DM1 therapy with advanced HER2-positive breast cancer after TKIs or HP therapy.
* The adverse events and prognosis of patients with advanced HER2-positive breast cancer who receive the T-DM1 therapy.
* Changes of anti-tumor immunity during T-DM1 therapy in patients with advanced HER2-positive breast cancer.

Participants will receive T-DM1 treatment (3.6mg/kg, d1/21, IVD) until progressive diseases or intolerable adverse effects occurs.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years; pregnancy test (-) for premenopausal and perimenopausal patients, promising to use reliable contraception during treatment.
* Patients who were be diagnosed with invasive breast cancer according to the eighth edition of American Joint Committee on Cancer (AJCC) staging system, and develop disease progression after anti-HER2 therapy (TKIs) for stage IV disease at initial diagnosis or within one year of adjuvant anti-HER2 therapy (HP) after surgery for early breast cancer.
* At least one measurable lesion according to RECIST 1.1.
* ECOG score of 0 or 1.
* The organ function is still good and meets the following indicators: hemoglobin ≥ 90g/L, white blood cell ≥ 3.5×10\^9/L, platelet ≥ 100×10\^9/L, neutrophil ≥ 1.5×10\^9/L, aspartate aminotransferase or alanine aminotransferase ≤ 3×ULN, total bilirubin ≤ 1.5×ULN, serum creatinine value ≤ 1.5×ULN.
* Without myocardial ischemia in ECG.
* NYHA grade I; Echocardiography LVEF ≥55%; Cardiac markers: cardiac troponin (cTnI) and brain natriuretic peptide (BNP) within normal range.
* Complete all necessary baseline laboratory and radiological tests prior to treatment.
* Complete clinical data.

Exclusion Criteria:

* male breast cancer or inflammatory breast cancer.
* Patients who have other malignant tumors or have contracted malignant tumors other than breast cancer in the past 5 years, except for basal cell carcinoma of the skin or flat cell carcinoma and carcinoma in situ of the cervix that have been adequately treated and controlled.
* Accompanying other anti-tumor treatments or participating in other clinical trials.
* Serious diseases that will affect the patient's compliance or put the patient at risk.
* Major surgical procedures performed within 4 weeks prior to the commencement of study treatment or anticipated major surgical procedures during the course of the study.
* Patients who have used ADC drugs at present or before this study.
* History of allergic reactions or contraindications to use of any drug ingredient in this study.
* Patients with chronic diarrhea and intestinal obstruction, as well as other diseases that affect drug administration and absorption.
* Patients who have clinical cardiac symptoms or diseases that are not well controlled, such as: heart failure above NYHA 2; unstable angina; myocardial infarction occurred within one year; clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
* Dementia, intellectual abnormality, or any mental illness that interferes with the understanding of informed consent.

Primary outcomes:
measure: Objective response rate
timeFrame: up to 12 months
Secondary outcomes:
measure: Progression-free survival
timeFrame: up to 36 months
measure: Overall survival
timeFrame: up to 36 months
measure: Adverse events
timeFrame: every 6 weeks
measure: Antitumor immunity related parameters
timeFrame: up to 12 weeks
measure: Tumor related parameters
timeFrame: up to 12 weeks
Other outcomes:
Locations:
city: Nanjing
country: China
facility: JiangSu Province Hospital/ The First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
References:
citation: Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763.
citation: Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF; American Society of Clinical Oncology; College of American Pathologists. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013 Nov 1;31(31):3997-4013. doi: 10.1200/JCO.2013.50.9984. Epub 2013 Oct 7.
citation: Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortes J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. doi: 10.1056/NEJMoa1413513.
citation: Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortes J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. doi: 10.1016/S1470-2045(19)30863-0. Epub 2020 Mar 12.
citation: Peddi PF, Hurvitz SA. Trastuzumab emtansine: the first targeted chemotherapy for treatment of breast cancer. Future Oncol. 2013 Mar;9(3):319-26. doi: 10.2217/fon.13.7.
citation: Hunter FW, Barker HR, Lipert B, Rothe F, Gebhart G, Piccart-Gebhart MJ, Sotiriou C, Jamieson SMF. Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer. Br J Cancer. 2020 Mar;122(5):603-612. doi: 10.1038/s41416-019-0635-y. Epub 2019 Dec 16.
citation: Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Dieras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov 8;367(19):1783-91. doi: 10.1056/NEJMoa1209124. Epub 2012 Oct 1.
citation: Krop IE, Kim SB, Gonzalez-Martin A, LoRusso PM, Ferrero JM, Smitt M, Yu R, Leung AC, Wildiers H; TH3RESA study collaborators. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Jun;15(7):689-99. doi: 10.1016/S1470-2045(14)70178-0. Epub 2014 May 2.
citation: Ding S, Chen X, Shen K. Single-cell RNA sequencing in breast cancer: Understanding tumor heterogeneity and paving roads to individualized therapy. Cancer Commun (Lond). 2020 Aug;40(8):329-344. doi: 10.1002/cac2.12078. Epub 2020 Jul 12.
citation: Gao Y, Wu N, Wang S, Yang X, Wang X, Xu B. Concurrent mutations associated with trastuzumab-resistance revealed by single cell sequencing. Breast Cancer Res Treat. 2021 Jun;187(3):613-624. doi: 10.1007/s10549-021-06237-0. Epub 2021 Apr 27.