Phase 2 Trial of Selinexor (KPT-330) for Metastatic Triple Negative Breast Cancer (TNBC)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: Selinexor
Intervention description: Participants will receive selinexor twice weekly on Monday/Wednesday, Tuesday/Thursday or Wednesday/Friday of Weeks 1, 2 and 3 of each 4-week cycle. Selinexor will not be taken during Week 4. One cycle is defined as 28 days or 6 doses. The starting dose for this trial is 60 mg (flat dose as long as their dose-based body surface area (BSA) analysis does not exceed 70 mg/m^2).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Triple Negative Breast Cancer (TNBC); Breast - Female; Breast - Male; Metastatic Triple Negative Breast Cancer; Receptor Tyrosine-protein Kinase erbB-2 (HER2) Negative; Erythroblastosis virus oncogene B (erbB)

Summary:

      The main purpose of this study is to see whether the combination of selinexor (KPT-330) can
      help people with triple negative breast cancer (TNBC). Researchers also want to study the
      safety and tolerability of Selinexor in TNBC patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed triple negative breast cancer (TNBC), defined as negative
             immunohistochemical staining for estrogen and progesterone receptors (≤5% of nuclei
             positive by IHC) and receptor tyrosine-protein kinase erbB-2 (HER2) negative (IHC 0-1+
             or HER2-neu negative according to American Society of Clinical Oncology; College of
             American Pathologists (ASCO-CAP) HER2 Test Guideline Recommendations)

          -  Written informed consent in accordance with federal, local, and institutional
             guidelines

          -  Body surface area ≥1.4 m^2

          -  Age ≥18 years

          -  Estimated life expectancy of >3 months at study entry

          -  TNBC must be either locally recurrent or metastatic. Locally recurrent disease must
             not be amenable to surgical resection or radiation with curative intent.

          -  Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

          -  Documented disease progression at study entry

          -  Must have received at least 1 chemotherapy regimens in the setting of metastatic
             disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

          -  Adequate hematological function: Absolute neutrophil count (ANC) > 1500/mm^3,
             platelets count >100,000mm^3

          -  Adequate hepatic function within 14 days prior to Cycle 1 Day 1 (C1D1): total
             bilirubin <2 times the upper limit of normal (ULN) (except patients with Gilbert's
             syndrome who must have a total bilirubin of < 3 times ULN) and aspartate
             aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5 x ULN. In the case of
             known (radiological and/or biopsy documented) liver metastasis, AST/ALT ≤5.0 times ULN
             is acceptable.

          -  Amylase and lipase ≤ 1.5 x ULN

          -  Adequate renal function within 14 days prior to C1D1: estimated creatinine clearance
             of ≥ 30 mL/min

          -  Women of child-bearing potential (WOCBP) must agree to use dual methods of
             contraception and have a negative serum pregnancy test at screening, and male
             participants must use an effective barrier method of contraception if sexually active
             with a female of child-bearing potential. For both male and female participants,
             effective methods of contraception must be used throughout the study and for 3 months
             following the last dose. To be considered of non-childbearing potential,
             postmenopausal women must be amenorrheic for at least 12 months naturally (not in the
             setting of post chemotherapy) or participants must be surgically sterile.

          -  Must have received prior anthracycline and taxane therapy unless clinically
             contraindicated

        Exclusion Criteria:

          -  Significant medical illness that in the investigator's opinion cannot be adequately
             controlled with appropriate therapy or would compromise the participant's ability to
             tolerate this therapy

          -  Women who are pregnant or lactating

          -  Radiation, chemotherapy, or immunotherapy or any other approved anticancer therapy ≤2
             weeks prior to cycle 1 day 1

          -  Major surgery within 4 weeks before Day 1

          -  Unstable cardiovascular function: Electrocardiogram (ECG) abnormalities requiring
             treatment, or congestive heart failure (CHF) of New York Hearth Association (NYHA)
             Class ≥3; myocardial infarction (MI) within 3 months

          -  Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals
             within one week prior to first dose. Potential participants with controlled infection
             or on prophylactic antibiotics are permitted in the study.

          -  Known history of HIV

          -  Known active hepatitis A, B, or C infection that requires treatment

          -  Any underlying condition that would significantly interfere with the absorption of an
             oral medication

          -  Grade >2 peripheral neuropathy at baseline (within 14 days prior to cycle 1 day 1)

          -  Participation in an investigational anti-cancer study within 3 weeks prior to Cycle 1
             Day 1

          -  Coagulation problems and active major bleeding within 4 weeks prior to C1D1 (peptic
             ulcer, epistaxis, spontaneous bleeding)

          -  Active central nervous system (CNS) malignancy. Asymptomatic small lesions are not
             considered active. Treated lesions may be considered inactive if they are stable for
             at least 3 months.

          -  Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks
             prior to Cycle 1 Day 1 or radio-immunotherapy ≤ 4 weeks prior to Cycle 1 Day 1

          -  Have not recovered to Grade ≤ 1 or to their baseline from clinically significant
             adverse effects