We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

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

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: NCT03095612
Recruitment Status : Active, not recruiting
First Posted : March 29, 2017
Last Update Posted : November 18, 2022
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
David E Gerber, University of Texas Southwestern Medical Center

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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: Selinexor Drug: Docetaxel Phase 1 Phase 2

Detailed 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).This study will compare safety and outcomes with historical controls (docetaxel monotherapy).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 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
Official Title: An Investigator-sponsored, Phase 1/2 Trial of the Oral XPO1 Inhibitor Selinexor (KPT-330) Monotherapy and in Combination With Docetaxel for Previously Treated, Advanced KRAS Mutant Non-small Cell Lung Cancer (NSCLC)
Actual Study Start Date : March 22, 2018
Actual Primary Completion Date : November 8, 2022
Estimated Study Completion Date : November 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Selinexor Monotherapy and in Combination with Docetaxel

For the selinexor monotherapy cohort, 6 patients each will be treated in two dosing cohorts (weekly and biweekly). Selinexor once weekly oral (40mg, 60mg, 80mg) OR Selinexor twice weekly oral (60mg, 40mg, 60mg weekly).

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, 40 mg once weekly. Docetaxel 75 mg/m2 IV, 60 every 3 weeks.

Drug: Selinexor
Selinexor once weekly oral or twice weekly oral
Other Name: KPT-330

Drug: Docetaxel
Docetaxel once every 3 weeks (75 mg/m2 IV)

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Tumor size will be assessed using the RECIST v1.1 [ Time Frame: Each 21 day cycle for 2 years ]
    To evaluate the efficacy of selinexor monotherapy and in combination with docetaxel in patients with advanced KRAS mutant NSCLC. Tumor size will be assessed at baseline and every 2 cycles (ie, after 7 weeks for first 2 cycles, and then every 6 weeks) during the treatment period using the Response Evaluation Criteria in Solid Tumors RECIST v1.1 criterion.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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. However, the Investigator should not repeat procedures that are performed as part of standard of care (SOC), if they are within the screening window and are done prior to signing the ICF.
    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 mutations detected by sequencing) by a CLIA-certified assay (source documentation required).
    6. Tissue available for analysis at time of enrollment for biomarker analysis: 10 unstained slides plus 1 H+E slide. If archival tumor tissue is not available in select cases, subjects may be permitted to enroll on the study with prior approval of the study PI.
    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) for advanced NSCLC.
    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. Patients may be transfused with PRBCs up to 7 days prior to when enrollment labs are drawn to achieve Hgb ≥9.0 mg/dL.
    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. 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
      • 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).

    13. Measurable disease according to RECIST v1.1
    14. 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.
    15. Previous treatment-associated clinically significant toxicities resolved to CTCAE grade ≤2 (except alopecia) or to their baseline. NOTE: Prior immunotherapy-related endocrinopathy controlled with ongoing medical management (eg, hypothyroidism, adrenal insufficiency, diabetes) is permitted
    16. 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. Concurrent active malignancy that would interfere with treatment administration or assessment in the opinion of the treating investigator
    5. 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
    6. 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
    7. Pre-existing grade 3 or 4 neuropathy
    8. Active Hepatitis A, B or C infection
    9. Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study)
    10. 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
    11. Prior exposure to docetaxel, selinexor, or another selective inhibitor of nuclear transport (SINE) compound (NOTE: prior docetaxel exposure permitted in selinexor monotherapy cohort)
    12. Patients unwilling to comply with study protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03095612

Layout table for location information
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, Pennsylvania
University of Pittsburgh Medical Center-Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
University of Vanderbilt Medical Center-Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75063
United States, Washington
University of Washington-Seattle Cancer Care Alliance
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Karyopharm Therapeutics Inc
Layout table for additonal information
Responsible Party: David E Gerber, Professor of Medicine, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT03095612    
Other Study ID Numbers: STU 032017-003
First Posted: March 29, 2017    Key Record Dates
Last Update Posted: November 18, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action