Testing a new targeted therapy (DS-8201a) against ado-trastuzumab emtansine (T-DM1) for patients with advanced-stage breast cancer previously treated with trastuzumab and taxane.

Phase 1

• Conditions: nresectable/metastatic breast cancer with human epidermal growth factor receptor 2 (HER2)-positive expression; MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-000222-61-ES
• Lead Sponsor: Daiichi Sankyo Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-10-09
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Adults =18 years old. (Please follow local regulatory requirements if the legal age of consent for study participation is >18 y old.)
• Pathologically documented breast cancer that:
- is unresectable or metastatic
- has confirmed HER2 positive expression as determined according to American Society of Clinical Oncology – College of American Pathologists guidelines evaluated at a central laboratory.
- was previously treated with trastuzumab and taxane in the advanced/metastatic setting or progressed within 6 mo after neoadjuvant or adjuvant treatment involving a regimen including trastuzumab and taxane.
• Documented radiologic progression (during or after most recent treatment or within 6 mo after completing adjuvant therapy).
• Subjects must be HER2 positive as confirmed by central laboratory assessment of most recent tumor tissue sample available.
• Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 4.5 mo after the last dose of DS 8201a or 7 mo after the last dose of T-DM1
• Adequate renal function, defined as:
- Creatinine clearance = 30 mL/min, as calculated using the Cockcroft-Gault equation
• Adequate hepatic function, defined as:
- Total bilirubin = 1.5 × upper limit of normal (ULN) if no liver metastases or < 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline
and
- Aspartate transaminase (AST)/alanine transaminase (ALT) = 5 × ULN
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 285
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 215

Exclusion Criteria

• Prior treatment with an anti-HER2-antibody drug conjugate (ADC).
• Uncontrolled or significant cardiovascular disease, including any of the following:
- History of myocardial infarction within 6 mo before randomization
- History of symptomatic congestive heart failure (New York Heart Association Class II to IV)
- Troponin levels consistent with myocardial infarction as defined according to the manufacturer within 28 d prior to randomization
- Corrected QT interval prolongation to > 470 ms (females) or > 450 ms (male) based on average of Screening triplicate 12 lead electrocardiogram (ECG)
- Left ventricular ejection fraction (LVEF) < 50% within 28 d prior to randomization
• Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
• Spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
- Subjects with clinically inactive brain metastases may be included in the study.
- Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified