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A phase 2 non-randomized study to assess the safety and efficacy of the combination of tucatinib and trastuzumab with capecitabine for the treatment of leptomeningeal metastases in HER2-neu positive breast cancer.
Full description
The purpose of this study is to evaluate a new treatment for patients with HER2+ metastatic breast cancer (MBC) with leptomeningeal disease (LMD). This is a rare and fast-growing form of cancer. Leptomeningeal disease refers to the seeding of tumor cells to the leptomeninges and dissemination in the cerebrospinal fluid.
Currently, there are is no standard of care treatment for LMD. However, we think the combination therapy will be safe and well-tolerated and may also improve survival. Blood and spinal fluid samples will be collected to evaluate the effects on the body and the cancer, which will help provide greater understanding to therapy response in patients.
The study has a two-stage design with the first stage including 15 subjects from up to ten institutions nationwide. If it advances to the second stage based on the number of successes, another 15 subjects will be enrolled.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Men and women, age ≥18 years at time of consent
Histologically proven metastatic infiltrating carcinoma of the breast that is HER2 positive - Immunohistochemistry (IHC) 3+ and/or Fluorescence in situ hybridization (FISH) ratio >2.0, or average HER2 copy number >6.0 signals per cell or per current ASCO-CAP (American Society of Clinical Oncology - College of American Pathologists) or NCCN (National Comprehensive Cancer Network) guidelines. (NOTE: HER2 testing may be performed on primary and/or metastatic site; Any estrogen and progesterone [ER/PR] status is allowed.)
Evidence of leptomeningeal disease (LMD) as diagnosed by a) presence of malignant cells in CSF (+CSF cytology) and/or b) Magnetic Resonance Imaging (MRI) evidence of LMD, plus clinical signs and/or symptoms. NOTE: Measurable extra-CNS disease is not required. Note: Patients who have MRI evidence of focal LMD with negative cytology and no symptoms are not eligible for enrollment.
Karnofsky Performance Status ≥ 50 or Eastern Cooperative Oncology Group (ECOG) ≤ 3
Patient is able and willing to undergo study-required testing including:
Patients who are on steroids due to CNS disease or LMD diagnosis should be on a stable dose for at least 5 days prior to registration.
Prior treatment allowances are as follows:
>14 days since last dose of any previous endocrine therapy, chemotherapy, trastuzumab or other antibody-based therapy. NOTE: If patients have been previously receiving trastuzumab on a weekly basis (at a dose of 2mg/kg), only a 7 day washout will be required.
>14 days or five half-lives since previous treatment with any experimental agent, whichever is greater
Cumulative dose of doxorubicin >360 mg/m2 or previous treatment with another anthracycline with cumulative dose equivalent to >360 mg/m2 doxorubicin is not allowed.
Patients must not have received any therapy specifically directed at LMD, including prior systemic or intrathecal therapy for LMD.
Radiotherapy:
Patients must not have received radiotherapy to the neuroaxis following diagnosis of LMD for the purpose of treating LMD, and may not receive
Patients must not have received whole brain radiotherapy for parenchymal metastases within the last 2 weeks (14 days) or focal CNS radiotherapy within 1 week (7 days) prior to first dose of study drug. Note: Radiation for the purpose of palliation in the setting of a painful bone or dural metastasis can be allowed at the discretion of the treating physicians.
All toxicity related to prior cancer therapies must have resolved to ≤ Grade 1, with the following exceptions: alopecia; neuropathy, which must have resolved to ≤ Grade 2; and CHF, which must have been ≤ Grade 1 in severity at the time of occurrence, and must have resolved completely. Must be without significant systemic illness (e.g. infection unresponsive to treatment after 7 days)
Adequate hematologic, liver, and renal function, as follows:
Left ventricular ejection fraction (LVEF) must be within institutional limits of normal as assessed by ECHO or MUGA documented within 4 weeks prior to enrollment on the study.
Able to understand the study requirements and document informed consent indicating his/her awareness of the investigational nature and the risks of this study.
Exclusion criteria
Primary purpose
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17 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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