A study to compare the efficacy and safety of SYD985 to four standard available treatments in patients with HER2-positive unresectable locally advanced or metastatic breast cancer.
- Conditions
- breast tumoursMedDRA version: 21.1Level: LLTClassification code 10006317Term: Breast tumour malignantSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001994-18-SE
- Lead Sponsor
- Byondis BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 423
Any patient must meet the following inclusion criteria:
1. Female patients, age = 18 years old at the time of signing informed consent;
2. Patients with histologically-confirmed, unresectable locally advanced or metastatic breast cancer;
3. Patients should have had either progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after (ado-)trastuzumab emtansine treatment for locally advanced or metastatic disease;
4. HER2-positive tumour status according to the ASCO-CAP guidelines (defined as a 3+ score on immunohistochemistry (IHC) and/or positive by in situ hybridization (ISH)) confirmed by the central laboratory;
5. Patients must have measurable or non-measurable disease that is evaluable per Response Evaluation Criteria for Solid Tumours (RECIST version 1.1). Patients with bone-only sclerotic disease without a lytic component are not eligible;
6. Eastern Cooperative Oncology Group (ECOG) performance status = 2;
7. Estimated life expectancy > 12 weeks at randomization;
8. Adequate organ function, evidenced by the following (local) laboratory results:
–Absolute neutrophil count = 1.5 x 109/L;
–Platelet count = 100 x 109/L;
–Hemoglobin = 9.0 g/dL;
–Total bilirubin = 1.5 x the upper limit of normal (ULN);
–Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3.0 x ULN (or = 5.0 x ULN in the presence of liver metastases);
–Serum creatinine = 1.5 x ULN;
9. For women of childbearing potential two methods of effective contraception must be used during the study and up to 6 months after last study treatment. This is not required in case the patient or sole partner is surgically sterilized or in case the patient truly abstains from sexual activity.
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 322
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 101
Any patient who meets any of the exclusion criteria below must be excluded from participation in the study:
1. Having been treated with:
a. SYD985 at any time;
b. Anthracycline treatment within 12 weeks prior to randomization;
c. Other anticancer therapy including chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to randomization;
d. Radiotherapy within 2 weeks prior to randomization;
e. Hormone therapy within 1 week prior to randomization;
The patient must have sufficiently recovered from any treatment-related toxicities to NCI CTCAE Grade = 1 (except for toxicities not considered a safety risk for the patient at the investigator’s discretion);
2. History of infusion-related reactions and/or hypersensitivity to trastuzumab, (ado-)trastuzumab emtansine or excipients of the study drug which led to permanent discontinuation of the treatment;
3. History of keratitis;
4. Severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) at screening;
5. Left ventricular ejection fraction (LVEF) < 50% as assessed by either echocardiography or multigated acquisition (MUGA) scan at screening, or a history of clinically significant decrease in LVEF during previous treatment with trastuzumab or (ado-)trastuzumab emtansine leading to permanent discontinuation of treatment;
6. Cardiac troponin value above the ULN (local laboratory) at screening;
7. History (within 6 months prior to randomization) of clinically significant cardiovascular disease such as unstable angina, congestive heart failure (CHF), myocardial infarction, uncontrolled hypertension, or cardiac arrhythmia requiring medication;
8. Untreated brain metastases, symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within 8 weeks prior to randomization. Patients with prior treatment of brain metastasis must have evidence of disease stability on baseline brain imaging as compared to historical brain imaging;
9. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan;
10. Known active Hepatitis B or C infection;
11. Major surgery within 4 weeks prior to randomization;
12. Pregnancy or lactation;
13. Other condition, which in the opinion of the investigator, would compromise the safety of the patient or the patient's ability to complete the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to demonstrate that SYD985 is superior to physician’s choice in prolonging PFS on the basis of the blinded independent central review of tumour assessment. ;Secondary Objective: The secondary objectives of this study are to compare the two treatment groups with respect to:<br>•Overall survival (OS);<br>•Objective response rate (ORR) on the basis of the blinded independent central review;<br>•Investigator assessed PFS;<br>•Patient reported outcomes for health related quality of life;<br>•Safety and tolerability.<br>;Primary end point(s): The primary endpoint of this study is to demonstrate that SYD985 is superior to physician’s choice in prolonging PFS on the basis of the blinded independent central review of tumour assessment.;Timepoint(s) of evaluation of this end point: As per trial flow chart documented in the protocol.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The secondary efficacy endpoints are:<br>• Overall Survival;<br>• Objective Response Rate on the basis of the blinded independent central review;<br>• Investigator assessed PFS;<br>• Patient reported outcomes for health related quality of life;<br><br>;Timepoint(s) of evaluation of this end point: As per trial flow chart documented in the protocol.