HER2-positive Breast Cancer
Conditions
Brief summary
This study (EXTEND trial) is a multicentre, interventional, prospective, randomised, open-label, controlled neoadjuvant, phase 2 trial evaluating the efficacy and safety of T-DXd monotherapy vs. standard-of-care docetaxel+ trastuzumab + pertuzumab (THP) in medium-risk (lymph node negative with a primary tumour stage T2) HER2-positive early breast cancer.
Interventions
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female, age ≥18 years at randomisation 2. Participants with invasive, untreated Locally assessed HER2-positive (IHC 3+ or ISH+) according to ASCO-CAP guidelines (Wolff et al 2018), maximum 6 weeks before registration 3. Clinical stage at presentation (based on mammogram or breast MRI assessment): cT2 (\>2cm, ≤5cm ), cN0, M0 as determined by the AJCC staging system, 8th edition (Hortobagyi et al 2017). 4. Written informed consent: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol. 5. LVEF ≥ 50% within 28 days before randomisation 6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 7. Adequate organ and bone marrow function within 14 days before randomisation as described: Platelet Count ≥ 100000/mm3; Haemoglobin ≥ 9.0 g/dL; Absolute neutrophil count ≥ 1500/mm3; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3×ULN; Total Bilirubin ≤ 1.5×ULN; Serum albumin ≥ 2.5 g/dL; CrCL ≥ 30 mL/min as determined by Cockcroft Gault (using actual body weight). International normalised ratio or Prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN. All parameters must be the most recent results available. Note: Transfusion (red blood cell or platelet) or G-CSF administration is not allowed within 14 days prior to the day on which bone marrow function is assessed, or at any time after this day and prior to C1D1. 8. Adequate treatment washout period before randomisation, defined as: Major Surgery ≥ 4 weeks; Radiation Therapy including palliative stereotactic radiation therapy to chest ≥ 4 weeks; Palliative stereotactic radiation therapy to other anatomic areas including whole brain radiation (see
Exclusion criteria
2) ≥ 2 weeks; Anti-Cancer chemotherapy \[Immunotherapy (non-antibody based therapy)\], retinoid therapy, hormonal therapy ≥ 3 weeks; Antibody based anti-cancer therapy ≥ 4 weeks; Targeted agents and small molecules ≥ 2 weeks or 5 half-lives, whichever is longer; Nitrosoureas or mitomycin C ≥ 6 weeks; TKIs approved for treatment of NSCLC ≥ 1 week; Chloroquine/Hydroxychloroquine ≥ 14 days; Cell-free and Concentrated Ascites Reinfusion Therapy (CART), peritoneal shunt or drainage of pleural effusion, ascites or pericardial effusion ≥2 weeks prior to screening assessment. 9. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner. For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU/mL) must be available at the screening visit and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of study treatment. Women of childbearing potential are defined as those who are not surgically sterile (i.e., underwent bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. 10. Female participants must not donate, or retrieve for their own use, ova from the time of enrolment and throughout the study treatment period, and for at least 7 months after the final study drug administration. They should refrain from breastfeeding throughout this time. Preservation of ova may be considered prior to enrollment in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery | Up to approximately 1 year | pCR rate after neoadjuvant treatment, defined as the proportion of participants who have no evidence by H&E staining of residual invasive disease in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by investigator assessment following completion of neoadjuvant therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety including adverse events (AEs), severe adverse events (SAEs) and adverse events of special interest (AESI). | Up to approximately 1.5 years | Incidence of AEs, SAE, AESIs (interstitial lung disease, LVEF decrease), AEs resulting in study intervention interruption and discontinuation, etc. |
| Event-free survival (EFS) rate at 12, 24, 36-month | Up to approximately 3 years | EFS is defined as time from date of randomisation until disease progression precluding initial surgery, invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause. |
| Invasive disease-free survival (IDFS) rate at 12, 24, 36-month | Up to approximately 3 years | IDFS is defined as time from surgery until invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause. |
| European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 Questionnaire (QLQ-C30) score | Up to approximately 3 years | The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. |
| EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR45) score | Up to approximately 3 years | The EORTC-QLQ-BR45 is a 45-item questionnaire developed to assess the quality of life of breast cancer patients. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. |
Countries
China
Contacts
Primary ContactZhimin Shao, Professor
Outcome results
None listed