A Randomised Trial Comparing Trastuzumab Deruxtecan to CDK4/6 Inhibitors in Non-luminal A, ER-positive/HER2-low Metastatic Breast Cancer

NCT ID: NCT06585969

Last Updated: 2024-10-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 504 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-01
• Study Completion Date: 2029-05-31

Brief Summary

The objective of this trial, DBCG R25, will be to evaluate the effect of trastuzumab-deruxtecan versus standard of care on progression-free survival (PFS) in first-line for patients with non-Luminal A, ER-positive/HER2-negative metastatic breast cancer

Detailed Description

Study design and setting We will conduct an international, multicentre, open-label, randomised controlled trial. All oncological departments who treat patients with metastatic breast cancer can participate. The EU Clinical Trial Regulation will be applied.

Interventions Trial participants will be randomised to trastuzumab deruxtecan or standard treatment.

Trastuzumab deruxtecan

Patients randomised to trastuzumab deruxtecan will be treated as:

Trastuzumab deruxtecan until progression or intolerable toxicity, Trastuzumab deruxtecan: 5.4 mg/kg intravenous on day 1 of a 21 days cycle.

Standard

Patients randomised to standard will be treated as:

CDK4/6 inhibitor with an endocrine therapy until progression or intolerable toxicity CDK4/6 inhibitor: Physician's choice of ribociclib (600mg daily for 21 days in a 28 days cycle) or abemaciclib (150mg twice daily).

Endocrine therapy: letrozole (2.5mg daily), anastrozole (1mg daily), exemestane (25mg daily), tamoxifen (20mg daily) or fulvestrant (intramuscular 500mg every 4 weeks)

Other treatment Prophylactic antiemetics are allowed, including corticosteroids. Prophylactic antibiotics are allowed if deemed necessary for the patient. G-CSF is allowed when needed.

All other symptomatic treatment to perform best of care is allowed as long as name, administration and length is documented in the chart. Bone targeted agents are allowed. No other antineoplastic treatment is allowed.

Radiological evaluation Patients will initially be scanned every 9-12 weeks as per investigator's or co-investigator's discretion with minimum a CT of the thorax and abdomen or a FDG-PET/CT. Patients with response can have this interval extended. Upon progression treatment/control is to be done according to department preferences, but subsequent treatment and day of death must be registered.

Conditions

Metastatic Breast Cancer; ER-positive Breast Cancer; Luminal B; Her2 Enriched; Basal Like

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trastuzumab-deruxtecan

Trastuzumab deruxtecan until progression or intolerable toxicity: 5.4 mg/kg intravenous on day 1 of a 21 days cycle.

Group Type: EXPERIMENTAL

Trastuzumab deruxtecan (T-DXd)

Intervention Type: DRUG

Trastuzumab deruxtexan every three weeks

Immunohistochemistry guided treatment (standard)

• CDK4/6 inhibitor with an endocrine therapy until progression og intolerable toxicity

• CDK4/6 inhibitor: Physician's choice of ribociclib (600mg daily for 21 days in a 4 week schedule) or abemaciclib (125mg twice daily).
• Endocrine therapy: letrozole (2.5mg daily), anastrozole (1mg daily), exemestane (25mg daily), tamoxifen (20mg daily) or fulvestrant (intramuscular 500mg every 4 weeks)

Group Type: ACTIVE_COMPARATOR

Ribociclib with ET

Intervention Type: DRUG

Ribociclib with endocrine therapy

Abemaciclib with ET

Intervention Type: DRUG

Abemaciclib with endocrine therapy

Interventions

Trastuzumab deruxtecan (T-DXd)

Trastuzumab deruxtexan every three weeks

Intervention Type: DRUG

Ribociclib with ET

Ribociclib with endocrine therapy

Intervention Type: DRUG

Abemaciclib with ET

Abemaciclib with endocrine therapy

Intervention Type: DRUG

Other Intervention Names

Enhertu

Eligibility Criteria

Inclusion Criteria

• Women aged 18 or above.
• Radiologically/pathologically verified metastatic breast cancer.
• ER-positive (1% or more) and HER2-low (HER2 1+ or HER2 2+/ISH-neg)10,11.
• PAM50 Luminal B, HER2-enriched or Basal-like.
• Performance status 0-1.
• Evaluable disease

Exclusion Criteria

• Patients who are incapable of understanding the written material received
• Patients with inaccessible tumour tissue
• Other malignant disease within 5 years (in situ cervix and non-melanoma skin cancer excluded)

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Danish Breast Cancer Cooperative Group

OTHER

Sponsor Role: lead

Responsible Party

Tobias Berg

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Tobias Berg, MD

Role: CONTACT

tobias.berg.01@regionh.dk

+45 38660669

Other Identifiers

DBCG-R25-DISCORDANT

Identifier Type: -

Identifier Source: org_study_id