Overview

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

Status:
Not yet recruiting
Trial end date:
2025-03-30
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
UNICANCER
Collaborators:
ARCAGY/ GINECO GROUP
Seagen Inc.
Treatments:
Hormones
Pertuzumab
Trastuzumab
Tucatinib
Criteria
Inclusion Criteria:

1. Male or female, Age ≥18;

2. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1;

3. Histologically confirmed HER2 positive breast cancer, with HER2 positive defined by in
situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ
hybridization (FISH) methodology;

4. 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);

5. Complete local treatment of brain progression (Surgery and/or radiation therapy)
should have been completed no more than 12 weeks before inclusion and there is no
clinical indication for immediate re-treatment with local therapy in the opinion of
the investigator;

6. Able to undergo MRI scanning of the brain;

7. Normal renal function: creatinine <1.5 x upper limit of normal (ULN);

8. 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);

9. Normal hematological function: Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L; platelets
count ≥100 x 10⁹/L; and hemoglobin ≥9.0 g/dL;

10. Adequate cardiac functions, including:

- 12 Lead electrocardiograms (ECG) with normal tracing or non-clinically
significant changes that do not require medical intervention

- QT/Corrected QT interval (QTc) ≤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

11. 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);

12. Stable dose of steroids at the time of enrolment;

13. Women of childbearing potential must have a negative pregnancy test (blood or urine
test) within 14 days prior to inclusion;

14. Woman of childbearing potential and male patients must agree to use adequate
contraception for the duration of trial participation and up to 7 months after
completing treatment/therapy (association of trastuzumab, pertuzumab +/- tucatinib).
Hormonal contraceptives such as birth control pills, patches, implants, or injections
are not allowed in patients who are hormone receptor positive;

15. Patient must have signed a written informed consent form prior to any trial specific
procedures. When the patient is physically unable to give their written consent, a
trusted person of their choice, independent from the investigator or the sponsor, can
confirm in writing the patient's consent;

16. Patients affiliated to the social security system (or equivalent);

17. Patient must be willing and able to comply with the protocol for the duration of the
trial including scheduled visits, treatment plan, laboratory tests, and examinations
including follow-up.

Exclusion Criteria:

1. 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;

2. Proven leptomeningeal disease;

3. Any progressive brain lesion between the brain local treatment completion and the
enrolment;

4. Poorly controlled seizures (more than 1/week);

5. Clinically significant cardiopulmonary disease;

6. 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

7. Previous treatment with a tyrosine kinase inhibitor;

8. Carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease;

9. Positive for human immunodeficiency virus (HIV);

10. Known prior severe hypersensitivity to tucatinib or compounds chemically or/and
biologically similar or any component in its formulation;

11. 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;

12. Pregnant women or women who are breast-feeding;

13. Inability to swallow tablets or significant gastrointestinal disease which would
preclude the adequate oral absorption of medications;

14. Person deprived of their liberty or under protective custody or guardianship or unable
to give informed consent;

15. Participation in another therapeutic trial within the 30 days prior to tucatinib
treatment initiation.