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Phase 1/2 Trial of Selinexor (KPT-330) With Docetaxel for Non-small Cell Lung Cancer (NSCLC)

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ClinicalTrials.gov Identifier: NCT03095612
Recruitment Status : Recruiting
First Posted : March 29, 2017
Last Update Posted : September 9, 2019
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date  ICMJE March 23, 2017
First Posted Date  ICMJE March 29, 2017
Last Update Posted Date September 9, 2019
Actual Study Start Date  ICMJE March 22, 2018
Estimated Primary Completion Date May 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 23, 2017)
Maximum Tolerated Dose (MTD) [ Time Frame: Each 21 day cycle for 2 years ]
A standard 3 + 3 dose escalation schedule will be used for all escalations. The selinexor will be taken starting 1 week for dose escalation at 60, 80, 100, 40 mg once per week every 3 weeks before the first docetaxel infusion. The docetaxel will be given the first day of each 21 day cycle at the dose of either 60 or 75 mg/m2 every 3 weeks.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03095612 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1/2 Trial of Selinexor (KPT-330) With Docetaxel for Non-small Cell Lung Cancer (NSCLC)
Official Title  ICMJE An Investigator-Sponsored, Phase 1/2 Trial of the Oral XPO1 Inhibitor Selinexor (KPT-330) in Combination With Docetaxel for Previously Treated, Advanced KRAS Mutant Non-small Cell Lung Cancer (NSCLC)
Brief Summary This study is being done to evaluate the safety of the investigational study drug, selinexor when given with docetaxel to patients who have been previously treated for advanced KRAS mutant lung cancer.
Detailed Description This is a phase 1/2 clinical trial of the oral XPO1 inhibitor selinexor (KPT-330) in combination with docetaxel for previously treated, advanced KRAS mutant non-small cell lung cancer (NSCLC). It is a single-arm, non-blinded study, which will compare safety and outcomes with historical controls (docetaxel monotherapy). The multi-center study will be conducted within the Academic Thoracic Oncology Medical Investigator Consortium (ATOMIC).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
This is a phase 1/2 single-arm, non-blinded, multi-institutional study. Selinexor will be administered once weekly starting one week before chemotherapy initiation (to permit pharmacodynamic assessment of selinexor alone and in combination with chemotherapy), in combination with docetaxel. Docetaxel will be given once every 3 weeks. Treatment will be administered in 21-day cycles. Dose limiting toxicities (DLTs) will be assessed based on the first cycle (7-day lead-in plus 21-day cycle = 28 days) toxicity using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03. A standard 3 + 3 dose escalation paradigm will be used.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE Drug: Selinexor
Oral XPO1 inhibitor selinexor (KPT-330) in combination with Docetaxel
Other Name: KPT-330
Study Arms  ICMJE Experimental: Selinexor in Combination with Docetaxel
Selinexor will be administered once weekly starting one week before chemotherapy initiation in combination with docetaxel. Docetaxel will be given once every 3 weeks. Treatment will be administered in 21-day cycles. Selinexor dose escalation: 60, 80, 100, 40 mg once weekly. Docetaxel 75 mg/m2 IV, 60 every 3 weeks.
Intervention: Drug: Selinexor
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 23, 2017)
59
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2021
Estimated Primary Completion Date May 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:

    1. Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
    2. Age ≥ 18 years
    3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
    4. Histologically or cytologically confirmed advanced (stage 4, according to the American Joint Committee on Cancer [AJCC] version 7.0 Staging manual) NSCLC
    5. Molecular identification of a KRAS mutation (codons 12, 13, or 61)
    6. Tissue available for analysis at time of enrollment for biomarker analysis (may be obtained via biopsy prior to initiation of treatment, or submission of available archival tissue): 10-15 slides, or 5 slides with 3 sections per slide
    7. At least one and up to two previous lines of systemic cytotoxic therapy for advanced NSCLC, of which one must have been a platinum-based doublet therapy. Up to four total previous lines of systemic therapy (including immunotherapy and molecularly targeted therapy)
    8. Radiographic or clinical disease recurrence or progression during or after the last line of systemic therapy
    9. Adequate hematologic function (absolute neutrophil count [ANC] ≥ 1500 cells/μL; hemoglobin ≥ 9 g/dL; platelets ≥ 100,000/μL. Use of PRBC transfusion to achieve Hgb ≥9.0 mg/dL is allowed.
    10. Adequate renal function (calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation)
    11. Adequate hepatic function (total bilirubin ≤ upper limit of normal [ULN], alanine aminotransferase [ALT] ≤ 2 × ULN and aspartate aminotransferase [AST] ≤ 2 × ULN). ALT and/or AST may be ≤ 5 × ULN if due to liver metastases. If ALT or AST is > 2 and ≤ 5 × ULN in patients with liver metastases, alkaline phosphatase must be ≤ 2.5 × ULN (unless elevated alkaline phosphatase clearly due to skeletal—rather than hepatic—process; eg, normal GGT, presence of multiple bone metastases, absence of bulky and/or central liver metastases). Patients with Gilbert's syndrome are allowed if total bilirubin ≤ 2 × ULN and direct bilirubin is ≤ ULN.
    12. Prothrombin time (PT) and/or international normalized ratio (INR) ≤ 1.5 × ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN if patient is not on anticoagulant therapy (a therapeutic PT and/or INR and aPTT is acceptable if the patient is on anticoagulants)
    13. Female patients of childbearing potential must agree to use 2 methods of contraception (including 1 highly effective and 1 effective method of contraception) and have a negative serum pregnancy test at Screening. Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment. Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use 2 reliable methods of contraception throughout the study and for 3 months after their last dose of medication. Female patients are considered NOT of childbearing potential if they have a history of surgical sterility (including hysterectomy and/or bilateral oophorectomy, but not tubal ligation alone) or evidence of post-menopausal status defined as any of the following:

      • Natural menopause with last menses >1 year ago and confirmed by FSH blood level
      • Radiation-induced oophorectomy with last menses >1 year ago
      • Chemotherapy-induced menopause with last menses >1 year ago. Male patients and their partners must use 2 reliable methods of contraception, at least one of them a barrier method (if sexually active with a female of child-bearing potential).
    14. Measurable disease according to RECIST v1.1
    15. Previously treated (surgery and/or radiation therapy) or untreated brain metastases are eligible, provided that patients are asymptomatic and not requiring escalating doses of corticosteroids
    16. Previous treatment-associated clinically significant toxicities resolved to CTCAE grade ≤1 (except alopecia) or to their baseline
    17. At least 3 weeks or 5 half-lives, whichever is shorter, since receiving systemic anticancer therapy, including investigational agents, prior to starting study therapy. At least 2 weeks since receiving radiation therapy prior to starting study therapy

Exclusion Criteria:

  • Patients meeting any of the following exclusion criteria are not eligible to enroll in this study:

    1. Patients who are pregnant or lactating
    2. Major surgery (excluding skin biopsies and procedures for insertion of central venous access devices) within 2 weeks of first dose of study drug
    3. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety
    4. Presence of symptomatic brain metastases or brain metastases requiring the escalating doses of corticosteroids to control neurological symptoms
    5. Other concurrent cancer (with the exception of non-melanoma skin cancer and low-risk localized prostate cancer on active surveillance)
    6. Unstable cardiovascular function:

      • Symptomatic ischemia, or
      • Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmics is excluded; 1st degree AV block or asymptomatic LAFB/RBBB are not excluded; asymptomatic rate controlled atrial fibrillation is not excluded), or
      • Congestive heart failure (CHF) of NYHA Class ≥3, or
      • Myocardial infarction (MI) within 3 months
    7. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral
    8. Pre-existing grade 3 or 4 neuropathy
    9. Active Hepatitis A, B or C infection
    10. Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study)
    11. Patients unable to swallow tablets, patients with malabsorption syndrome, or any other GI disease or GI dysfunction that could interfere with absorption of study treatment
    12. Prior exposure to docetaxel, selinexor, or another selective inhibitor of nuclear transport (SINE) compound
    13. Patients unwilling to comply with study protocol.
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: Joyce Bolluyt 214-648-7097 joyce.bolluyt@utsouthwestern.edu
Contact: David Principal Investigator, MD
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03095612
Other Study ID Numbers  ICMJE STU 032017-003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Texas Southwestern Medical Center
Study Sponsor  ICMJE University of Texas Southwestern Medical Center
Collaborators  ICMJE Karyopharm Therapeutics Inc
Investigators  ICMJE Not Provided
PRS Account University of Texas Southwestern Medical Center
Verification Date September 2019

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