Clinical Trials /

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

NCT02402764

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: MCC-18150
  • NCT ID: NCT02402764

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
SelinexorKPT-330, Selective Inhibitor of Nuclear Export (SINE)Selinexor Treatment

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Selinexor TreatmentExperimentalScreening 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).
  • Selinexor

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical Benefit Rate
Time Frame:Up to 10 months
Safety Issue:
Description: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 Outcome Measures

Measure:Best Overall Response (OR)
Time Frame:Up to 10 months
Safety Issue:
Description: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.
Measure:Duration of Overall Response
Time Frame:Up to 10 months
Safety Issue:
Description: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.
Measure:Progression-Free Survival (PFS)
Time Frame:Up to 10 months
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:End of post-treatment 12 month follow-up, up to 24 months per participant
Safety Issue:
Description:Overall survival, defined as the time from randomization to death from any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial 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)

Last Updated

December 12, 2017