FASN Inhibitor TVB-2640, Paclitaxel, and Trastuzumab in Treating Patients With HER2 Positive Advanced Breast Cancer

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Scottsdale/Phoenix, Arizona: 16-010066
    • Jacksonville, Florida: 16-010066
    • Rochester, Minnesota: 16-010066
    NCT ID: NCT03179904
    Sponsor Protocol Number: MC1633

About this study

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. FASN inhibitor TVB-2640 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and trastuzumab, 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. Giving FASN inhibitor TVB-2640, paclitaxel, and trastuzumab may work better in treating patients with HER2 positive breast cancer.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • PRE-REGISTRATION INCLUSION CRITERIA
  • 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 =< four (4) prior chemotherapy regimens in the metastatic setting
  • One of the following must be true:
    • Progressed on taxane-based chemotherapy in the metastatic setting OR
    • Metastatic disease was diagnosed during or =< 12 months after last dose of neoadjuvant or adjuvant taxane-based chemotherapy
  • One of the following must be true:
    • Progressed on trastuzumab and pertuzumab in the metastatic setting OR
    • Metastatic disease was diagnosed during or =< 6 months after last dose of neoadjuvant or adjuvant HER2-directed therapy
  • Unlimited prior endocrine therapy for hormone receptor positive disease
  • Willingness to provide mandatory tumor tissue specimens for correlative research
  • 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-positive advanced breast cancer; HER2+ is defined by 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
  • Hemoglobin >= 9.0 g/dL
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • Direct bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate transaminase (AST) =< 3 x ULN (=< 5 x ULN for patients with liver involvement)
  • Calculated creatinine clearance >= 45 ml/min using the Cockcroft-Gault formula
  • Cardiac ejection fraction (left ventricular ejection fraction [LVEF]) >= 50% by echocardiogram =< 30 days of registration
  • Provide written informed consent
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Negative urine pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
    • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Patient and his/her partner agree to use adequate contraception after providing written informed consent through 3 months after the last dose of TVB-2640, as follows:
    • For women: Compliant with a medically-approved contraceptive regimen during and for 3 months after the treatment period or documented to be surgically sterile or postmenopausal
    • For men: Compliant with a medically-approved contraceptive regimen during and for 3 months after the treatment period or documented to be surgically sterile; men whose sexual partners are of child-bearing potential must agree to use 2 methods of contraception prior to study entry, during the study, and for 3 months after the treatment period
  • Willingness to provide mandatory tumor tissue and/or blood specimens for correlative research

Exclusion Criteria:

  • 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
  • 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 >=12 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
  • Prior history of hypersensitivity, drug or radiation-induced, or other immune-mediated pneumonitis
  • Patient is unable to swallow oral medications or has impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption (e.g. active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome); concomitant therapy with proton pump inhibitors and/or H2-receptor antagonists is permissible
  • Patient has a history of clinically significant dry eye (xerophthalmia) or other corneal abnormality, or if a contact lens wearer, does not agree to abstain from contact lens use from baseline through the last TVB-2640 dose
  • Patients with a history of intolerance to trastuzumab (i.e. a grade 3 or 4 infusion reaction) are excluded; Note: patients with a history of mild infusion reaction to trastuzumab who have previously been successfully re-challenged after an infusion reaction with or without prophylactic medication are allowed
  • Other active malignancy =< 5 years prior to pre-registration
    • EXCEPTIONS: Non-melanoma skin cancer or carcinoma-in-situ of the cervix which has been adequately treated
    • NOTE: If there is a history of prior malignancy, patients must not be receiving other treatment for their cancer and the disease must be inactive/stable
  • REGISTRATION EXCLUSION CRITERIA
  • Any of the following:
    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Any of the following therapies prior to registration:
    • Chemotherapy =< 3 weeks
    • Immunotherapy =< 3 weeks
    • Biologic therapy =< 3 weeks
    • Hormonal therapy =< 2 weeks
    • Monoclonal antibodies =< 3 weeks
    • Radiation therapy =< 2 weeks
    • CDK 4/6 inhibitors =< 4 weeks
    • mTOR inhibitors =< 4 weeks

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Tufia Haddad, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Tufia Haddad, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Tufia Haddad, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

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CLS-20366138

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