Neoadjuvant Trastuzumab Deruxtecan (T-DXd) With Response-directed Definitive Therapy in Early Stage HER2-positive Breast Cancer (SHAMROCK Study)

NCT05710666 | Active Not Recruiting Phase 2

• 2 other identifiers: CTRIAL-IE 22-012022-002485-32
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 5

Brief Summary

This study is a Phase 2 open label, single arm, adaptive multi-centre trial. Patients with early stage HER2-positive breast cancer will receive neoadjuvant treatment of trastuzumab deruxtecan (T-DXd) 5.4mg/kg intravenously every three weeks for up to six cycles.

Conditions

HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• The percentage of patients who achieve pCR after T-DXd treatment

  The percentage of patients who achieve pCR after T-DXd treatment and thus avoid standard cytotoxic chemotherapy

  From registration until surgery, approximately 18 weeks

Secondary Outcomes (14)

• pCR rate in all other patients (patients who could not avoid standard cytotoxic chemotherapy) and in the entire study population.

  From registration until surgery, approximately 18 weeks

• 3-year EFS of patients treated with only T-DXd and trastuzumab.

  3 years from registration

• 3-year overall survival (OS) of patients treated with only T-DXd and trastuzumab.

  3 years from registration

• 3-year EFS of patients treated with systemic therapy other than trastuzumab in addition to T-DXd.

  3 years from registration

• 3-year OS of patients treated with systemic therapy other than trastuzumab in addition to T-DXd.

  3 years from registration

Study Arms (1)

T-DXd

EXPERIMENTAL

Drug: trastuzumab deruxtecan (T-DXd) (IV)

Interventions

trastuzumab deruxtecan (T-DXd) (IV) DRUG

Administered as an intravenous (IV) infusion at a dose of 5.4 mg/kg on Day 1 of each 21-day cycle for up to six cycles.

T-DXd

Eligibility Criteria

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

You may qualify if:

• Adult women and men ≥ 18 years of age.
• Histologically confirmed HER2-positive breast cancer:
• o Documented HER2 overexpression by local laboratory (IHC 3+ or FISH or CISH positive on diagnostic breast biopsy).
• Newly diagnosed breast cancer, planned for neoadjuvant therapy prior to surgery.
• Stages 2-3 breast cancer.
• Patients should not have received any prior therapy for breast cancer.
• Patients must be willing to undergo mandatory tumour biopsy at Cycle 2 Day 14 (+/- 4 days) and (if applicable, refer to section 9.5 Tomosynthesis-Guided Core Biopsies sub-study and Table 8-2) before surgery .
• ECOG performance status 0-1.
• Availability of archival tumour biopsy tissue at screening.
• Left ventricular ejection fraction (LVEF) ≥ 50%, as determined by ECHO or MUGA.
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (granulocyte-colony stimulating factor administration is not allowed within 1 week prior to C1D1)
• Platelet count ≥ 100 x 109/L (Platelet transfusion is not allowed within 1 week prior to C1D1)
• Haemoglobin ≥ 9.0 g/dL. NOTE: Participants requiring ongoing transfusions or growth factor support to maintain haemoglobin ≥9.0 g/dL are not eligible (Red blood cell transfusion is not allowed within 1 week prior to C1D1).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN)
• Total bilirubin ≤ 1.5xULN or \< 3×ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia)

You may not qualify if:

• Known metastatic or stage 4 breast cancer.
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction (MI) less than 6 months before registration, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Patients with troponin levels above ULN at screening and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out MI.
• Corrected QT interval (QTcF) prolongation to \>470 msec (females) or \>450 msec (males) based on the screening 12-lead ECG.
• Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion).
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration.
• Non-healing wound, ulcer, or bone fracture.
• Active, clinically serious infections \> CTCAE Grade 2 (CTCAE v5.0) requiring IV antibiotics, antivirals, or antifungals.
• Patients with evidence or history of bleeding diathesis. Any haemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study treatment.
• Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• 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.
• Lung criteria:
• Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months before study registration, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.)
• Any autoimmune, connective tissue or inflammatory disorders (e.g. Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for patients who are included in the study.
• Prior pneumonectomy (complete)
• Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of trastuzumab deruxtecan. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IMP.

Sponsors & Collaborators

• Cancer Trials Ireland: lead

Study Sites (5)

University Hospital Galway

Galway, Connacht, Ireland

Location

Saint Vincent's University Hospital

Dublin, Leinster, D4, Ireland

Location

Beaumont Hospital

Dublin, Leinster, D9, Ireland

Location

Cork University Hospital

Cork, Munster, Ireland

Location

University Hospital Limerick

Limerick, Munster, Ireland

Location

Related Publications (1)

• Dowling GP, Toomey S, Bredin P, Parker I, Mulroe E, Marron J, McLoughlin O, Teiserskiene A, Power C, O'Shea AM, Greally M, Morris PG, Duke D, Hill ADK, Hennessy BT. Neoadjuvant trastuzumab deruxtecan (T-DXd) with response-directed definitive therapy in early stage HER2-positive breast cancer: a phase II study protocol (SHAMROCK study). BMC Cancer. 2024 Jan 17;24(1):91. doi: 10.1186/s12885-024-11851-4.

  PMID: 38233810 DERIVED

MeSH Terms

Interventions

trastuzumab deruxtecan

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2022
• First Posted: February 2, 2023
• Study Start: October 26, 2023
• Primary Completion: September 30, 2025
• Study Completion (Estimated): March 30, 2028
• Last Updated: August 5, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

IE (5)