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Selinexor and Docetaxel in Treating Participants with Stage IV KRAS Mutant Non-Small Cell Lung Cancer

Trial Status: Active

This phase I / II trial studies the safety and best dose of selinexor and docetaxel in treating participants with stage IV KRAS-mutation non-small cell lung cancer that has spread to other places in the body. Selinexor may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving selinexor and docetaxel may work better in treating participant with stage IV KRAS mutant non-small cell lung cancer.

Inclusion Criteria

  • 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 informed consent form (ICF)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Histologically or cytologically confirmed advanced (stage 4, according to the American Joint Committee on Cancer [AJCC] version 7.0 Staging manual) NSCLC
  • Molecular identification of a KRAS mutation (codons 12, 13, or 61 mutations detected by sequencing) by a Clinical Laboratory Improvement Amendments (CLIA)-certified assay (source documentation required)
  • 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
  • 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)
  • Radiographic or clinical disease recurrence or progression during or after the last line of systemic therapy
  • Absolute neutrophil count [ANC] >= 1500 cells/uL
  • Hemoglobin >= 9 g/dL
  • Platelets >= 100,000/uL
  • Patients may be transfused with packed red blood cells (PRBCs) up to 7 days prior to when enrollment labs are drawn to achieve Hgb >= 9.0 mg/dL
  • Calculated creatinine clearance >= 30 mL/min using the Cockcroft-Gault equation
  • Total Bilirubin =< upper limit of normal [ULN]
  • ALT (alanine aminotransferase) =< 2 x ULN
  • AST (aspartate aminotransferase) =< 2 x ULN * NOTE: ALT and/or AST may be =< 5 x ULN if due to liver metastases. If ALT or AST is > 2 and =< 5 x ULN in patients with liver metastases
  • Alkaline phosphatase must be =< 2.5 x ULN (unless elevated alkaline phosphatase clearly due to skeletal—rather than hepatic—process; eg, normal gamma-glutamyltransferase (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 x ULN and direct bilirubin is =< ULN
  • PT (Prothrombin time) and/or international normalized ratio (INR) =< 1.5 x ULN
  • aPTT (activated partial thromboplastin time) =< 1.5 x ULN * NOTE: if patient is not on anticoagulant therapy (a therapeutic PT and/or INR and aPTT is acceptable if the patient is on anticoagulants)
  • 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 childbearing 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 follicle stimulating hormone (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)
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • 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
  • Previous treatment-associated clinically significant toxicities resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade =< 1 (except alopecia) or baseline
  • At least 3 weeks or 5 half-lives, whichever is shorter, since receiving systemic anticancer therapy, including investigational agents. At least 2 weeks since receiving radiation therapy

Exclusion Criteria

  • Patients who are pregnant or lactating
  • Major surgery (excluding skin biopsies and procedures for insertion of central venous access devices) within 2 weeks of first dose of study drug
  • Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient’s safety
  • Presence of symptomatic brain metastases or brain metastases requiring escalating doses of corticosteroids to control neurological symptoms
  • Other concurrent cancer (with the exception of non-melanoma skin cancer and low-risk localized prostate cancer on active surveillance)
  • Unstable cardiovascular function: * Symptomatic ischemia, or * Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmics are excluded; recent onset atrial fibrillation not in sinus rhythm and without cardiology evaluation are excluded; 1st degree AV block or asymptomatic left anterior fascicular block (LAFB)/right bundle branch block (RBBB) are not excluded), or * Congestive heart failure (chf) of New York Heart Association (NYHA) class >= 3, or * myocardial infarction (mi) within 3 months
  • 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
  • Active hepatitis A, B or C infection
  • Pre-existing grade 3 or 4 neuropathy
  • Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study)
  • Patients unable to swallow tablets, patients with malabsorption syndrome, or any other gastrointestinal (GI) disease or GI dysfunction that could interfere with absorption of study treatment
  • Prior exposure to docetaxel, selinexor, or another selective inhibitor of nuclear transport (SINE) compound
  • Patients unwilling to comply with study protocol

Colorado

Aurora
University of Colorado Hospital
Status: ACTIVE
Contact: Ross Camidge
Phone: 720-848-0300

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: ACTIVE
Contact: Timothy Francis Burns

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: ACTIVE
Contact: Leora Horn

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: David Eric Gerber
Phone: 214-648-4180

PRIMARY OBJECTIVES:

I. To determine the safety and the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of selinexor administered with the standard dose of docetaxel in patients with non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of selinexor in combination with docetaxel in NSCLC

EXPLORATORY OBJECTIVES:

I. To identify predictive and pharmacodynamic biomarkers of selinexor in combination with docetaxel.

OUTLINE: This is a dose escalation study of selinexor followed by a phase II study.

Participants receive selinexor orally (PO) once a week beginning on day -7. Participants also receive docetaxel intravenously (IV) over 60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up every 3 months.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
UT Southwestern / Simmons Cancer Center-Dallas

Principal Investigator
David Eric Gerber

  • Primary ID SCCC-04517; STU 032017-003
  • Secondary IDs NCI-2018-01282
  • Clinicaltrials.gov ID NCT03095612