Phase 2 Trial of Selinexor (KPT-330) for Metastatic Triple Negative Breast Cancer (TNBC)

Study Overview
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Brief Summary
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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.

Official Title
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Investigator-Initiated Phase 2 Clinical Trial of Selinexor (KPT-330) for the Treatment of Metastatic Triple Negative Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Selinexor


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selinexor Treatment<br>Screening period (which may last up to 28 days), followed by Selinexor treatment for qualified participants. During the treatment period, participants will undergo physical examination every 2 weeks until Cycle 6 Day 1 (C6D1), and then every 4 weeks and assessment of tumor response every 8 weeks. Participants will be treated until progression of disease or the development of unacceptable toxicities. All participants will then undergo a final visit (end of treatment visit). | Drug: Selinexor<br>* 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).<br>* Other names: Selective Inhibitor of Nuclear Export (SINE);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate | Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) ≥ 12 weeks of selinexor in patients with triple negative breast cancer (TNBC), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | Up to 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (OR) | The best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. | Up to 10 months | 
| Duration of Overall Response | The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) or death. The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented or death. | Up to 10 months | 
| Progression-Free Survival (PFS) | Median time to progression. Progression-free survival is defined as time elapsed from the beginning of study treatment to the first documentation of radiologic progression as defined by standard RECIST criteria or death. | Up to 10 months | 
| Overall Survival (OS) | Overall survival, defined as the time from randomization to death from any cause. | End of post-treatment 12 month follow-up, up to 24 months per participant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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)