Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluating SINE KPT-330 in Treating Patients With Melanoma That Cannot Be Removed By Surgery (KPT-330)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02120222
Recruitment Status : Unknown
Verified July 2017 by Kari Kendra, Ohio State University Comprehensive Cancer Center.
Recruitment status was:  Recruiting
First Posted : April 22, 2014
Last Update Posted : July 12, 2017
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
Kari Kendra, Ohio State University Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE April 17, 2014
First Posted Date  ICMJE April 22, 2014
Last Update Posted Date July 12, 2017
Actual Study Start Date  ICMJE May 27, 2014
Estimated Primary Completion Date July 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2014)
Incidence of adverse events graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: 28 days ]
Types of toxicities, incidences and severity will be summarized by descriptive statistics such as frequencies/proportions.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2014)
  • CBR (complete response, partial response, stable disease or stable disease) using Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 1 year ]
  • PFS [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause or last contact, assessed up to 1 year ]
    Kaplan-Meier method will be used to assess the PFS.
  • Change in tumor markers by immunohistochemistry [ Time Frame: Baseline to up to 1 year ]
    Markers with continuous numerical data will be analyzed using linear mixed effects models (LMEMs). Binary markers (presence vs. absence) will be summarized by proportions and the confidence intervals will be calculated. Marker changes by mutation groups in plots will be presented. To correlate the marker changes with response, mainly summary statistics and plots will be used given the potentially small subgroups.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluating SINE KPT-330 in Treating Patients With Melanoma That Cannot Be Removed By Surgery
Official Title  ICMJE A Phase 1 Expansion Cohort Evaluating the Selective Inhibitor of Nuclear Export (SINE) KPT-330 in Patients With Unresectable Melanoma
Brief Summary This phase I clinical trial studies the side effects of selinexor in treating patients with melanoma that cannot be removed by surgery. Drugs used in chemotherapy, such as selinexor, may stop the growth of tumor cells, by stopping them from dividing.
Detailed Description

PRIMARY OBJECTIVES:

I. To estimate safety of KPT-330 (selinexor) in patients with melanoma at the maximum tolerated dose (MTD) defined by the phase 1 study.

SECONDARY OBJECTIVES:

I. To determine the clinical benefit rate (CBR) (complete response, partial response, and stable disease) of patients with unresectable melanoma.

II. To assess the efficacy at the MTD as measured by progression free survival (PFS) in patients with melanoma.

TERTIARY OBJECTIVES:

I. To validate nuclear transport inhibition resulting from treatment. II. To assess if v-raf murine sarcoma viral oncogene homolog B1 (BRAF), neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS), or platelet-derived growth factor receptor, beta polypeptide (PDGFRB) mutational status impacts response.

III. To assess alteration in signaling pathways as a result of therapy with KPT-330.

IV. To assess immunologic changes resulting from treatment with KPT-330.

OUTLINE:

Patients receive selinexor orally (PO) twice weekly (BIW). Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 year

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent Melanoma
Intervention  ICMJE
  • Drug: selinexor
    Given PO
    Other Names:
    • CRM1 nuclear export inhibitor KPT-330
    • KPT-330
    • selective inhibitor of nuclear export KPT-330
    • SINE KPT-330
  • Other: Correlative studies
    Blood will be collected for pK and pDn analysis pretreatment on day 1 and 8 hours after treatment, on day 1 of cycles 1 and 2.
    Other Names:
    • pharmacological studies
    • pharmacokinetics
    • pharmacodynamics
Study Arms  ICMJE Experimental: Treatment (selinexor)
Patients receive selinexor PO BIW. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Blood will be collected for correlative studies to perform pK (pharmacokinetics) and pDn (pharmacodynamics) analysis pretreatment on day 1 and 8 hours after treatment, on day 1 of cycles 1 and 2.
Interventions:
  • Drug: selinexor
  • Other: Correlative studies
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: April 17, 2014)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2019
Estimated Primary Completion Date July 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent in accordance with federal, local, and institutional guidelines
  • Patients with unresectable melanoma
  • Patients must have received a biologic therapy (e.g. interleukin 2) and a BRAF and/or MEK inhibitor (if tumor contains the V600E or V600K mutation) for 628 metastatic disease. If patient did not receive such agents, rationale for not treating the patients with the 629 agent must be cleared with the study PI (ie no V600e/k BRAF mutation or patient with autoimmunity, thus 630 not eligible for biologic therapy).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Total white blood cell (WBC) count >= 3000/mm^3
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • 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)
  • Alanine aminotransferase (ALT) < 2.5 times ULN; in the case of known (radiological and/or biopsy documented) liver metastasis, ALT < 5.0 times ULN is acceptable
  • Estimated creatinine clearance of >= 50 mL/min, calculated using the formula of Cockroft and Gault
  • Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential; acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose

Exclusion Criteria:

  • Patients who are pregnant or lactating
  • Radiation, chemotherapy, immunotherapy or any other systemic anticancer therapy =< 2 weeks prior to initiation of therapy
  • Major surgery within four weeks before initiation of therapy
  • Unstable cardiovascular function:

    • Symptomatic ischemia, or
    • Uncontrolled clinically significant conduction abnormalities (e.g.: ventricular tachycardia on antiarrhythmics are excluded and 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded)
    • Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3, or
    • Myocardial infarction (MI) within 3 months of initiation of therapy
  • Uncontrolled active infection within one week prior to first dose
  • Known to be human immunodeficiency virus (HIV) seropositive
  • Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) ribonucleic acid (RNA) or HBsAg (hepatitis B virus [HBV] surface antigen)
  • Patients with active central nervous system (CNS) malignancy

    • Asymptomatic small lesions are not considered active
    • Treated lesions may be considered inactive if the patient is able to taper off steriods without any recurrent neurologic symptoms.
  • Patients will be excluded if they have had a major resection of the bowel that could influence absorption, inflammatory bowel disease, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation within 28 days prior to beginning study treatment
  • Grade >= 2 peripheral neuropathy within 14 days prior to initiation of therapy
  • History of seizures, movement disorders or cerebrovascular accident within the past 5 years
  • Patients with known macular degeneration or uncontrolled glaucoma
  • In the opinion of the investigator, patients who are significantly below their ideal body weight
  • Serious psychiatric or medical conditions that could interfere with treatment
  • Participation in an investigational anti-cancer study within 3 weeks prior to initiation of therapy
  • Concurrent therapy with approved or investigational anticancer therapeutic
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02120222
Other Study ID Numbers  ICMJE OSU-13124
NCI-2014-00676 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kari Kendra, Ohio State University Comprehensive Cancer Center
Study Sponsor  ICMJE Kari Kendra
Collaborators  ICMJE Karyopharm Therapeutics Inc
Investigators  ICMJE
Principal Investigator: Kari Kendra Ohio State University Comprehensive Cancer Center
PRS Account Ohio State University Comprehensive Cancer Center
Verification Date July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP