TVB-2640 and Trastuzumab With Paclitaxel or Endocrine Therapy for Treatment of HER2 Positive Metastatic Breast Cancer

Completed · Phase 2

Conditions studied: Advanced Breast Carcinoma, HER2-Positive Breast Carcinoma, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, HER2-positive Breast Cancer

In brief

This phase II trial studies how well FASN inhibitor TVB-2640, paclitaxel, and trastuzumab work in treating patients with HER2 positive breast cancer that has spread to other places in the body (metastatic). FASN inhibitor TVB-2640 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Trastuzumab is a form of targeted therapy because it attaches itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Estrogen can cause the growth of breast cancer cells. Drugs used in endocrine therapy either lower the amount of estrogen made by the body or blocks the use of estrogen by the tumor cells. This may help stop the growth of tumor cells that need estrogen to grow. Giving FASN inhibitor TVB-2640 and trastuzumab in combination with paclitaxel or endocrine therapy may help control the disease in patients with HER2 positive breast cancer.

Key facts

Study ID

NCT03179904

Run by

Mayo Clinic

People needed

17

Starts

2017-08-03

Expected to finish

2026-03-13

Last updated by the study team

2026-07-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• PRE-REGISTRATION INCLUSION CRITERIA
• Age >=18 years
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria that is:
• A non-nodal lesion is considered measurable if its longest diameter can be accurately measured as >= 1.0 cm with computed tomography (CT) scan, CT component of a positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) and/or
• A malignant lymph node is considered measurable if its short axis is > 1.5 cm when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm)
• Note: tumor lesions in a previously irradiated area are not considered measurable disease; disease that is measurable by physical examination only is not eligible
• Received =< six (6) prior chemotherapy regimens in the metastatic setting
• Cohort A one of the following must be true:
• Distant disease progression during administration of combination therapy with taxane based chemotherapy and anti-HER2 therapy (trastuzumab or pertuzumab) for metastatic disease
• Note: patients who began treatment with this combination and discontinued taxane-based chemotherapy due to intolerability before distant disease progression are eligible
• Distant disease progression during administration or within 180 days of discontinuing combination therapy with taxane based chemotherapy and anti-HER2 therapy (trastuzumab or pertuzumab) in the adjuvant disease
• Note: patients who began treatment with this combination and discontinued taxane-based chemotherapy due to intolerability before distant disease progression are eligible
• For patient who received taxane based chemotherapy and anti-HER2 therapy (trastuzumab or pertuzumab) in the neo-adjuvant setting and underwent surgical resection of primary breast disease: distant disease progression during or within 180 days of discontinuing anti-HER2 therapy (trastuzumab or pertuzumab) in the adjuvant setting
• Cohort B (one of the following must be true):
• Distant disease progression during administration of combination therapy with endocrine therapy and anti-HER2 therapy (trastuzumab or pertuzumab) for metastatic disease; permissible endocrine therapies include an aromatase inhibitor or fulvestrant
• NOTE: Tamoxifen is not permissible
• Distant disease progression during administration of combination therapy with endocrine therapy and anti-HER2 therapy (trastuzumab or pertuzumab) in the adjuvant setting; permissible endocrine therapies include an aromatase inhibitor or fulvestrant
• NOTE: Tamoxifen is not permissible
• Willingness to provide mandatory tumor tissue specimens for correlative research
• NOTE: If insufficient or no tissue is obtained by the pre-registration biopsy, an archival tissue specimen (preferably from a metastatic site) from procedure performed =< 5 years prior to pre-registration must be available to submit for Central Laboratory review prior to registration
• Exception: If there is no medically safe site for biopsy, Study Chair (Dr. Haddad) may waive this requirement
• REGISTRATION INCLUSION CRITERIA
• Registration must be completed =< 28 days of pre-registration
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Histological confirmation of HER2-expression (immunohistochemistry [IHC] 1-3+) on pre-registration biopsy. (HER2+ is defined by 2018 American Society of Clinical Oncology/College of American Pathologists [ASCO/CAP] guidelines)

You may not qualify if…

• PRE-REGISTRATION EXCLUSION CRITERIA
• Patients who previously discontinued trastuzumab due to unacceptable cardiac toxicity
• Patients with a history of LVEF decline to below 50% during or after prior trastuzumab or other HER2 directed therapy =< 6 months prior to pre-registration
• Patients with any class of New York Heart Association (NYHA) congestive heart failure (CHF) or heart failure with preserved ejection fraction (HFPEF)
• Patients with a history of known coronary artery disease or a myocardial infarction within 12 months prior to pre-registration
• Patients with persistently uncontrolled hypertension (systolic blood pressure [BP] > 160 mm Hg or diastolic BP > 100 mm Hg) despite optimal medical therapy
• Patients with known unstable angina pectoris
• Patients with a known history of serious cardiac arrhythmias requiring treatment (exception: controlled atrial fibrillation, paroxysmal supraventricular tachycardia)
• Patients with a prolonged corrected QT interval (QTc) interval (>= 450 ms)
• Leptomeningeal disease or uncontrolled brain metastasis
• NOTE: Metastases treated by surgery and/or radiotherapy such that patient is neurologically stable and off steroids >= 4 weeks prior to preregistration are eligible
• Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment
• EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment
• Tumors involving spinal cord or heart
• Visceral crisis or lymphangitic spread
• NOTE: Visceral crisis is not the mere presence of visceral metastases, but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of disease
• Uncontrolled intercurrent non-cardiac illness including, but not limited to,
• Ongoing or active infection
• Psychiatric illness/social situations
• Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
• Or any other conditions that would limit compliance with study requirements
• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
• NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

Where it is running

• Mayo Clinic in Arizona — Scottsdale, Arizona, United States
• Mayo Clinic in Florida — Jacksonville, Florida, United States
• Mayo Clinic in Rochester — Rochester, Minnesota, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.