Breast Cancer
Conditions
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)
Brief 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.
Interventions
DRUGSelinexor
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).
Sponsors
Karyopharm Therapeutics Inc
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate | Up to 10 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response (OR) | Up to 10 months | 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. |
| Duration of Overall Response | Up to 10 months | 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. |
| Progression-Free Survival (PFS) | Up to 10 months | 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. |
| Overall Survival (OS) | End of post-treatment 12 month follow-up, up to 24 months per participant | Overall survival, defined as the time from randomization to death from any cause. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at Moffitt Cancer Center between July 2015 and January 2016.
Participants by arm
| Arm | Count |
|---|---|
| Selinexor Treatment Ten patients were treated with oral selinexor 60 mg twice per week (on days 1 and 3) on a schedule of 3 weeks on and 1 week off, each four-week cycle. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Selinexor Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 60 years |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 3 / 10 |
Outcome results
Primary
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.
Time frame: Up to 10 months
Population: All participants
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Selinexor Treatment | Clinical Benefit Rate | Complete Response | 0 Participants |
| Selinexor Treatment | Clinical Benefit Rate | Partial Response | 0 Participants |
| Selinexor Treatment | Clinical Benefit Rate | Stable Disease | 3 Participants |
| Selinexor Treatment | Clinical Benefit Rate | Progressive Disease | 7 Participants |
Secondary
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.
Time frame: Up to 10 months
Population: Participants with Complete Response or Partial Response
Secondary
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.
Time frame: Up to 10 months
Population: Participants with Complete Response or Partial Response
Secondary
Overall Survival (OS)
Overall survival, defined as the time from randomization to death from any cause.
Time frame: End of post-treatment 12 month follow-up, up to 24 months per participant
Population: All participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Selinexor Treatment | Overall Survival (OS) | 6.0 months |
Secondary
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.
Time frame: Up to 10 months
Population: All participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Selinexor Treatment | Progression-Free Survival (PFS) | 1.0 months |