T-DXd Versus THP for Medium-risk HER2-positive Early Breast Cancer

NCT06548178 | Not Yet Recruiting Phase 2

• 1 other identifier: SCHBCC-N077
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 1

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.

Conditions

HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  Up to approximately 1 year

Secondary Outcomes (5)

• Safety including adverse events (AEs), severe adverse events (SAEs) and adverse events of special interest (AESI).

  Up to approximately 1.5 years

• Event-free survival (EFS) rate at 12, 24, 36-month

  Up to approximately 3 years

• Invasive disease-free survival (IDFS) rate at 12, 24, 36-month

  Up to approximately 3 years

• European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 Questionnaire (QLQ-C30) score

  Up to approximately 3 years

• EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR45) score

  Up to approximately 3 years

Study Arms (2)

Arm A

EXPERIMENTAL

T-DXd (5.4 mg/kg Q3W on Day 1) ×6 cycles.

Drug: T-DXd

Arm B

PLACEBO COMPARATOR

Docetaxel (75 mg/m2 Q3W on Day 1) concurrent with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg Q3W on Day 1) and pertuzumab (840 mg loading dose followed by 420 mg Q3W on Day 1) × 6 cycles.

Drug: THP

Interventions

T-DXd DRUG

T-DXd (5.4 mg/kg Q3W on Day 1) ×6 cycles.

Arm A

THP DRUG

Docetaxel (75 mg/m2 Q3W on Day 1) concurrent with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg Q3W on Day 1) and pertuzumab (840 mg loading dose followed by 420 mg Q3W on Day 1) × 6 cycles.

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female, age ≥18 years at randomisation
• 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
• 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).
• 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.
• LVEF ≥ 50% within 28 days before randomisation
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1
• 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.

You may not qualify if:

• 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.
• 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.
• Non-operable breast cancer including inflammatory breast cancer
• Any previous history of invasive breast cancer
• Multiple primary malignancies within 3 years, with the exception of
• adequately resected non-melanoma skin cancer
• curatively treated in-situ disease
• other solid tumors curatively treated
• Any evidence for existing metastatic disease (confirmed by CT Thorax/Abdomen, bone scan, or other methods according to clinical practice
• Previous or concurrent treatment with cytotoxic agents for any reason (except non-oncological reasons)
• Concurrent treatment with other experimental drugs and participation in another clinical trial with any investigational drug within 30 days prior to study entry
• Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study/inadequate organ function
• Reasons indicating risk of poor compliance
• Woman of child-bearing potential defined as a woman physiologically capable of becoming pregnant, and not using highly effective methods of contraception during the study treatment and for 3 months after stopping the treatment.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

Central Study Contacts

Zhimin Shao, Professor

CONTACT

86-021-64175590; zhimingshao@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 4, 2024
• First Posted: August 12, 2024
• Study Start: September 1, 2024
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2028
• Last Updated: August 12, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)