Global open label phase-III study having 3 treatment arm in neoadjuvant setting in Patients with High-risk HER 2-positive Early-stage Breast Cancer
- Conditions
- Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
- Registration Number
- CTRI/2022/01/039210
- Lead Sponsor
- ASTRAZENECA AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
1.Male or female participants greater than or equal to 18 years of age.
2.Histologically documented HER2-positive EBC participants with (a) Locally assessed HER2-positive (IHC 3+ or ISH+) according to ASCO-CAP guidelines (see Appendix N) and prospectively centrally confirmed as HER2-positiveWolff et al 2018 based on a tumour sample.
(b) Unifocal and multifocal tumours ( > 1 tumour confined to the same quadrant as the primary tumour) must have 1 focus sampled and centrally confirmed as HER2-positive.
(c) Multi-centric tumours (multiple tumours involving > 1 quadrant of the breast) must have 1 lesion from each involved quadrant sampled and centrally confirmed as HER2-positive. All quadrants tested must be centrally confirmed as HER2 positive.
(d) Tumours documented as HR-positive (either ER and/or PgR positive [ER or PgR greater than or equal to 1%]) or HR-negative (ER and PgR negative) by local assessment per ASCO-CAP guidelines.
(e) Clinical stage at presentation (based on mammogram or breast MRI assessment): T0-4 (inclusive of inflammatory breast cancer), N1-3, M0 or greater than or equal to T3, N0, M0 as determined by the AJCC staging system, 8th edition.(f) Pathologic confirmation of nodal involvement with malignancy as determined by fine-needle aspiration or core-needle biopsy, when applicable.
3.Must have an adequate FFPE tumour tissue sample available for assessment of HER2 by central laboratory (either from an archival diagnostic biopsy or a newly obtained biopsy). At least 2 cores must be provided in the form of FFPE tissue blocks
4.ECOG performance status of 0 or 1 at randomisation.
5.Adequate organ and bone marrow function during screening:
6.LVEF greater than or equal to 50% within 28 days before randomisation.
7.Negative pregnancy test (serum) for women of childbearing potential who are sexually active with a non-sterilised male partner.
8.Female participants must be 1 year post-menopausal, surgically sterile, or using one highly effective form of non-hormonal birth control. Women of childbearing potential who are sexually active with a non-sterilised male partner must agree to use one highly effective method of non-hormonal birth control. They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study to 7 months after the last dose of study treatment or as dictated by local prescribing information for SOC treatments received after neoadjuvant treatment. Female participants must refrain from egg cell donation and breastfeeding while on study and for 7 months after the last dose of study treatment or as dictated by prescribing information for SOC treatments received after neoadjuvant treatment. Non-sterilised male partners of a woman of childbearing potential must use a male condom plus spermicide (condom alone in countries where spermicides are not approved) throughout this period.
9.Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of screening throughout the total duration of the study and for 6 months after the last dose of study intervention or as dictated by local prescribing information for SOC treatments received after neoadjuvant treatment to prevent pregnancy in a partner. Male participants must not donate or bank sperm during thi
Medical conditions
1.Prior history of invasive breast cancer.
2.Stage IV breast cancer as determined by AJCC staging system, 8th edition.
3.Any primary malignancy within 3 years, except adequately resected non-melanoma skin cancer, or curatively treated in situ disease.
4.History of DCIS, except for participants treated with mastectomy only > 5 years prior to current diagnosis.
5.As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including ongoing or active infection, uncontrolled hypertension, renal transplant and active bleeding diseases, serious chronic gastrointestinal conditions associated with diarrhoea) which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
6.Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
7.Active hepatitis C infection. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Participants with current active or history of hepatitis B infection with either HBsAg(+) or anti-HBc(+) are not eligible
8.Active primary immunodeficiency or known to have tested positive for HIV or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
9.Participants with a medical history of myocardial infarction within 6 months before enrolment, symptomatic CHF (NYHA Class II to IV), unstable angina pectoris, or a recent ( < 6 months) cardiovascular event including stroke. Participants with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrolment to rule out myocardial infarction.
10.Investigator judgement of 1 or more of the following:
(a) Mean resting corrected QTcF interval > 470 ms (females) or > 450 ms (males), obtained from triplicate ECGs performed at screening.
(b) History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause TdP.
(c) Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
11.History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the Study Physician.
12.History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
13.Lung criteria:
(a) Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of study enrolment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method