Treatment With Tucatinib in Patients With an Isolated Brain Progression of a Metastatic Breast Cancer

NCT05041842 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: UC-BCG-20112020-005735-79
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 16

Brief Summary

The overall survival of patients with metastatic breast cancer has steadily improved over the past decades, mainly due to advances in systemic treatment. Despite these advances, the development of brain metastases remains a serious and devastating complication that decreases quality of life and increases morbidity and mortality. The HER2CLIMB randomized study demonstrated that adding the investigational drug tucatinib to the standard treatment trastuzumab and capecitabine improved both progression-free survival and overall survival in people diagnosed with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer, previously treated with trastuzumab, pertuzumab, and T-DM1. In patients with brain metastases, the 1-year progression-free survival was 25% in the tucatinib group and 0% in the placebo group. These results suggest that tucatinib may be a new standard treatment for HER2-positive metastatic disease. The aim of the non-randomized phase II study, InTTercePT, is to evaluate the effectiveness of adding tucatinib to trastuzumab and pertuzumab in the event of cerebral progression, after the end of local treatment.

Conditions

Metastatic Breast Cancer With a Isolated Brain Progression

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  The progression-free survival is defined as the proportion of patients with an objective tumor progression by imaging, or death from any cause, whichever occurs first at 6 months from inclusion. Progression will be determined locally by the investigator through the use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in case of lesions identified at baseline. For patients without any evidence of evidence at inclusion, the progression will be defined as an appearance of a new lesion (measurable or not measurable).

  6 months

Secondary Outcomes (4)

• Overall Survival

  Throughout study completion, up to 18 months

• Brain Progression-Free Survival

  Throughout study completion, up to 18 months

• Overall brain metastasis response

  Throughout study completion, up to 18 months

• Incidence of treatment-emergent Adverse Events

  Throughout study completion, up to 18 months

Study Arms (1)

Tucatinib plus systemic treatment with or without hormone therapy

EXPERIMENTAL

Addition of tucatinib to the systemic treatment (pertuzumab and trastuzumab) with or without hormone therapy.

Drug: Tucatinib; Drug: Pertuzumab; Drug: Trastuzumab; Drug: Hormone therapy; Drug: Pertuzumab/ Trastuzumab

Interventions

Tucatinib DRUG

300 mg orally twice daily

Tucatinib plus systemic treatment with or without hormone therapy

Pertuzumab DRUG

Initial loading: 840 mg Maintenance: 420 mg, 3-weekly

Also known as: Perjeta®

Tucatinib plus systemic treatment with or without hormone therapy

Trastuzumab DRUG

Intravenous formulation : Initial loading: 8 mg/kg Maintenance: 6 mg/kg, 3-weekly Subcutaneous formulation: 600 mg (fixed dose regardless of patient's body weight), 3-weekly

Also known as: Herceptin® or Biosimilar

Tucatinib plus systemic treatment with or without hormone therapy

Hormone therapy DRUG

Anastrozole (1 mg/day) or letrozole (2.5 mg/day) or fulvestrant (2x250 mg at day 1 and day 15 then every 4 weeks after the first injection)

Tucatinib plus systemic treatment with or without hormone therapy

Pertuzumab/ Trastuzumab DRUG

Initial loading: 1200 mg Pertuzumab / 600 mg Trastuzumab (regardless of body weight) Maintenance: 600 mg Pertuzumab / 600 mg Trastuzumab (regardless of body weight), 3-weekly

Also known as: Phesgo®

Tucatinib plus systemic treatment with or without hormone therapy

Eligibility Criteria

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

You may qualify if:

• Male or female, Age ≥18;
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1;
• Histologically confirmed HER2 positive breast cancer, with HER2 positive defined by in situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization (FISH) methodology;
• Documented isolated brain progression (defined as new or progressive brain metastases with stable or responding systemic disease) under pertuzumab and trastuzumab treatment (with or without taxane) for metastatic disease (There is no limit to the number and size of brain metastasis);
• Able to undergo MRI scanning of the brain;
• Normal renal function: creatinine \<1.5 x upper limit of normal (ULN);
• Adequate liver function: total bilirubin ≤1.5 ULN (unless documented Gilbert's syndrome); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 ULN (≤5 ULN in the presence of liver metastases);
• Normal hematological function: Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L; platelets count ≥100 x 10⁹/L; and hemoglobin ≥9.0 g/dL;
• Adequate cardiac functions, including:
• Lead electrocardiograms (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention
• QT/Corrected QT interval (QTcF) ≤470 msec for woman and ≤450 msec for men (mean of replicate values, correction per institutional standard) on the ECG at the screening visit and a normal kalemia
• Left ventricular ejection fraction (LVEF) ≥50%
• No history of Torsades de Pointes or other symptomatic QTc abnormality
• Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 5.0 Grade 1 or to baseline (except alopecia or others toxicities not considered a safety risk for the patient at investigator's discretion);
• Stable dose of steroids at the time of enrolment;

You may not qualify if:

• Radiologic extra-cranial progression under pertuzumab and trastuzumab treatment, at the time of enrolment. The systemic disease must be stable or responding at the time of enrolment;
• Proven leptomeningeal disease;
• Any progressive brain lesion between the brain local treatment completion and the enrolment;
• Poorly controlled seizures (more than 1/week);
• Clinically significant cardiopulmonary disease;
• Used of a strong cytochrome P450 (CYP)2C8 inhibitor within 5 half-lives of the inhibitor, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment. Use of sensitive CYP3A substrates should be avoided one week before enrollment and during study treatment
• Previous treatment with a tyrosine kinase inhibitor;
• Carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease;
• Positive for human immunodeficiency virus (HIV);
• Known prior severe hypersensitivity to tucatinib or compounds chemically or/and biologically similar or any component in its formulation;
• History of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless the patient has been in remission and off all other cancer therapy for at least 3 years;
• Pregnant women or women who are breast-feeding;
• Inability to swallow tablets or significant gastrointestinal disease which would preclude the adequate oral absorption of medications;
• Person deprived of their liberty or under protective custody or guardianship or unable to give informed consent;
• Participation in another therapeutic trial within the 30 days prior to tucatinib treatment initiation.

Sponsors & Collaborators

• UNICANCER: lead
• Seagen Inc.: collaborator
• ARCAGY/ GINECO GROUP: collaborator

Study Sites (16)

Institut de Cancérologie de l'Ouest - Site Paul Papin

Angers, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre Francois Baclesse

Caen, France

Location

Centre Georges François Leclerc

Dijon, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

Centre Leon Berard

Lyon, France

Location

Hôpital privé Jean Mermoz

Lyon, France

Location

Institut du cancer de Montpellier

Montpellier, 34090, France

Location

Centre Antoine Lacassagne

Nice, France

Location

CARIO - Centre Armoricain Radiothérapie Imagerie Médicale et Oncologi

Plérin, France

Location

Centre Hospitalier Annecy Genevois

Pringy, France

Location

Institut Jean Godinot

Reims, France

Location

Centre Henri Becquerel

Rouen, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Centre Hospitalier Universitaire de Tours

Tours, France

Location

Gustave Roussy

Villejuif, France

Location

MeSH Terms

Interventions

tucatinib; pertuzumab; Trastuzumab; Biosimilar Pharmaceuticals

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Thomas Bachelot, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

• Anne-Claire Hardy-Bessard, MD

  Centre Armoricain d'Oncologie

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Patients treated with pertuzumab and trastuzumab for metastatic breast cancer who will develop an isolated brain relapse treated with local treatment will receive tucatinib in addition to pertuzumab and trastuzumab. Tucatinib will be taken orally 300 mg twice a day, pertuzumab (420 mg) and trastuzumab (6 mg/kg) will be taken every 3 weeks.

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: September 13, 2021
• Study Start: December 17, 2021
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2026
• Last Updated: November 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (16)