Trial Title:
Tucatinib With Brain and/or Spinal XRT in Patients With HER2+ Metastatic Breast Cancer and LMD
NCT ID:
NCT06016387
Condition:
HER2-positive Breast Cancer
LMD
Conditions: Official terms:
Breast Neoplasms
Capecitabine
Trastuzumab
Tucatinib
Conditions: Keywords:
HER2+
Breast Cancer
Leptomeningeal disease
Tucanitib
CLIMB-LMD
HER2 CLIMB LMD
CLIMB LMD HER2+
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tucatinib 150 MG
Description:
Tucatinib is a potent, selective, adenosine triphosphate-competitive small-molecule
inhibitor of the receptor tyrosine kinase HER2. The molecular formula for tubatinib is
C26H24N8O2 and it has a molecular weight of 480.52 g/mol.
Arm group label:
Tucatinib, Transtuzumab, Capecitabine
Other name:
Tukysa
Intervention type:
Drug
Intervention name:
Trastuzumab
Description:
MYL-1401O contains the active substance trastuzumab, which is an IgG1 monoclonal
antibody. The molecular size of the intact molecule is around 148 kDa.
Each vial of MYL-1401O contains 150 mg of lyophilized proposed active biosimilar
substance trastuzumab as well as 3.36 mg L-Histidine Hydrochloride, 2.16 mg L-Histidine,
115.2 mg sorbitol and 33.6 mg PEG-3350 (Macrogol 3350). Sorbitol and PEG-3350 substitute
the α- trehalose dehydrate and polysorbate-20, which are used as excipients in the
EU-approved and US-licensed Herceptin formulations.
Arm group label:
Tucatinib, Transtuzumab, Capecitabine
Intervention type:
Drug
Intervention name:
Capecitabine
Description:
Capecitabine is a tumour-activated antineoplastic agent (antimetabolite). The molecular
formula for capecitabine is C15H22FN3O6 and has a molecular weight of 359.35 g/mol.
Arm group label:
Tucatinib, Transtuzumab, Capecitabine
Intervention type:
Radiation
Intervention name:
Brain & Spinal Radiation
Description:
Brain & Spinal XRT is a treatment for patients with HER2+ metastatic breast cancer and
leptomeningeal disease,
Arm group label:
Tucatinib, Transtuzumab, Capecitabine
Other name:
Brain & Spinal XRT
Summary:
The proposed study will evaluate the safety and efficacy of XRT followed by systemic
therapy among patients with HER2+ metastatic breast cancer and LMD
Detailed description:
Breast cancer is the most common cancer among women worldwide, and the second leading
cause of brain metastases (BrM). Despite recent treatment advances, the prognosis of
patients with breast cancer BrM remains poor, and the prognosis among those with
leptomeningeal disease (LMD) is particularly dire with a median survival of only 2-4
months.
Patients with HER2+ metastatic breast cancer have a high life-time risk of central
nervous system (CNS) metastases, with an approximately 50% lifetime risk. Although the
cause of death among patients with breast cancer BrM is challenging to ascertain,
approximately 50% of patients with HER2+ BrM are thought to die from central nervous
system (CNS) disease involvement. Among patients with LMD specifically, the cause of
death is most commonly related to CNS disease.
In an analysis of 430 patients (96 of whom had breast cancer) treated for LMD in the
National Cancer Database between 2005 and 2014, those patients treated with chemotherapy
plus radiotherapy had a longer median overall survival of 5 months (3.5 - 6.5 months)
compared to patients treated with XRT or chemotherapy alone. In addition, a majority
(n=18/26, 69%) of observational studies irrespective of primary tumor site have shown an
"improvement or likely improvement" in survival with the use of XRT for LMD, either alone
or in combination with systemic therapy. Hence, this proposed study will evaluate the
safety and efficacy of XRT followed by systemic therapy (which is considered standard of
care) among patients with HER2+ metastatic breast cancer and LMD.
Criteria for eligibility:
Criteria:
Inclusion Criteria: Phase 1
1. Men or women with HER2+ metastatic breast cancer.
2. Evidence of LMD in the brain and/or spine
3. Age 18+ at time of consent;
4. ECOG ≤ 2;
5. If applicable, the last dose of prior chemotherapy, immunotherapy, endocrine therapy
therapy must have been completed 14 days prior to study enrollment.
6. More than 14 days or 5 half-lives from the last dose of any experimental agent is
required, whichever is greater;
7. All toxicity related to prior cancer therapies must have resolved to ≤ Grade 1 prior
to enrollment, except for alopecia; neuropathy, must have resolved to ≤ Grade 2.
Phase 2: Inclusion Criteria
1. Left ventricular ejection fraction (LVEF) must be within institutional limits of
normal as assessed by ECHO or MUGA documented within 2 weeks prior to starting
systemic therapy on the study;
2. Adequate hematologic, liver, and renal function within 2 weeks prior to phase 2
enrollment, as follows:
1. Hemoglobin ≥ 9 g/dL
2. ANC ≥ 1 x109/L
3. Platelets ≥ 100 x109/L
4. Total bilirubin ≤ 1.5 X upper limit of normal (ULN)
5. AST and ALT ≤ 2.5X ULN
6. International normalized ratio (INR) and activated partial thromboplastin time
(aPTT) ≤ 1.5 X ULN
7. Creatinine clearance (CrCL) ≥ 50 mL/min
Exclusion Criteria: Phase 1
1. Prior WBRT for brain metastases
2. Prior therapy specifically directed at LMD
3. Inability to comply with MRI-based surveillance of CNS disease.
4. Inability to swallow pills or any significant gastrointestinal diseases such as
inflammatory bowel disease.
5. Presently known dihydropyrimidine dehydrogenase deficiency;
6. Diagnosed with Hereditary fructose intolerance;
7. Diagnosed with Gilbert's disease;
8. Prior history of other cancer with evidence of disease within the last 5 years;
9. Prior use of tucatinib at any time prior to enrollment.
Phase 2:
1. Currently pregnant or breastfeeding;
2. Use 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 the
first dose of systemic therapy
3. Myocardial infarction or unstable angina within 6 months prior to the first dose of
systemic therapy.
4. Blood product transfusions in order to meet eligibility criteria
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The Ottawa Hospital
Address:
City:
Ottawa
Country:
Canada
Status:
Recruiting
Contact:
Email:
climb-lmd@sunnybrook.ca
Facility:
Name:
Sunnybrook Health Sciences Centre
Address:
City:
Toronto
Zip:
M4N 3M5
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Katarzyna Jerzak, MD
Email:
katarzyna.jerzak@sunnybrook.ca
Contact backup:
Last name:
Clarissa Chau
Email:
clarissa.chau@sunnybrook.ca
Investigator:
Last name:
Arjun Sehgal, MD
Email:
Sub-Investigator
Investigator:
Last name:
Katarzyna Jerzak, MD
Email:
Principal Investigator
Start date:
November 25, 2023
Completion date:
October 5, 2028
Lead sponsor:
Agency:
Sunnybrook Health Sciences Centre
Agency class:
Other
Collaborator:
Agency:
Seagen Inc.
Agency class:
Industry
Collaborator:
Agency:
Biocon Biologics
Agency class:
Other
Source:
Sunnybrook Health Sciences Centre
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06016387
