phase 2 trial of selinexor (kpt-330) for metastatic triple negative breast cancer (tnbc)

Conditions: Breast Cancer

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

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)