Selinexor in Treating Patients With Relapsed Small Cell Lung Cancer
Condition: Recurrent Small Cell Lung Carcinoma
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: Selinexor; Laboratory Biomarker Analysis; Pharmacological Study
Intervention description: Given PO; Correlative studies; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Small Cell Lung Cancer

Summary:

      This phase II trial studies how well selinexor work in treating patients with small-cell lung
      cancer that has returned after a period of improvement. One specific way cancer cells
      continue to grow is by getting rid of certain proteins called "tumor suppressor proteins:
      that would normally cause cancer cells to die. Selinexor works by trapping "tumor suppressing
      proteins" within the cell and may cause the cancer cells to die or stop growing.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent in accordance with federal, local, and institutional
             guidelines

          -  Patients should have estimated life expectancy of > 3 months at study entry

          -  Patients with relapsed small cell lung cancer - diagnosis must be histologically
             confirmed

          -  Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at the
             time of study entry

          -  Objective evidence of disease progression on study entry

          -  Prior systemic anticancer therapy: patients will have received no more than 2 prior
             chemotherapy regimens; the regimen(s) may have included biological, molecularly
             targeted or immune therapies; patients with primary refractory disease (i.e., those
             patients with progressive disease on first line chemotherapy) and patients with
             disease relapse within 90 days of completion of initial chemotherapy (chemotherapy
             resistant) are excluded; patients with limited stage small cell lung cancer (SCLC) and
             systemic relapse who are not felt to be candidates for repeat platinum-based
             chemotherapy at relapse are eligible for enrollment

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Absolute neutrophil count (ANC) > 1000/mm^3

          -  Platelet count > 75,000 mm^3

          -  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)

          -  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

          -  Albumin >= 3.0 mg/dl

          -  Estimated creatinine clearance of >= 30 mL/min, calculated using the formula of
             Cockroft and Gault

          -  Amylase =< 1.5 x ULN

          -  Lipase =< 1.5 x ULN

          -  Alkaline phosphatase limit =< 2.5 x ULN

          -  Female patients of childbearing potential must agree to use dual methods 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 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

          -  Resolution to grade =< 1 by National Cancer Institute (NCI) Common Terminology
             Criteria for Adverse Events (CTCAE v4.03) of all clinically significant toxic effects
             of prior anti-cancer therapy (with the exception neuropathy, which may be =< grade 2
             within 14 days prior to cycle 1 day 1)

          -  Available archival tumor tissue or willingness to undergo repeat biopsy is required at
             trial initiation

        Exclusion Criteria:

          -  Primary refractory disease (progressive disease on initial platinum based
             chemotherapy) or chemotherapy-resistant disease (disease progression within 90 days of
             completion of initial chemotherapy)

          -  Patients who are pregnant or lactating

          -  Radiation, chemotherapy, or immunotherapy or any other anticancer therapy =< 2 weeks
             prior to cycle 1 day 1; any clinical trial therapy (including investigational
             anti-cancer study) =< 3 weeks prior to cycle 1 day 1

          -  Prior treatment with selinexor

          -  Major surgery within 3 weeks before day 1

          -  Unstable cardiovascular function:

               -  Electrocardiogram (ECG) abnormalities requiring treatment, or

               -  Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3

               -  Myocardial infarction (MI) within 3 months

               -  Symptomatic ischemia or angina

          -  Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals
             within one week prior to first dose; patients with controlled infection or on
             prophylactic antibiotics are permitted in the study

          -  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) RNA or hepatitis B surface antigen (HBsAg) (hepatitis B virus [HBV]
             surface antigen)

          -  Serious psychiatric or medical conditions that could interfere with treatment

          -  History of seizures, movement disorders or cerebrovascular accident within the past 5
             years prior to cycle 1 day 1

          -  Concurrent therapy with approved or investigational anticancer therapeutic other than
             steroids

          -  Patients with > 3 liver metastases at time of enrollment

          -  Patients with coagulation problems and active bleeding in the last month (peptic
             ulcer, epistaxis, spontaneous bleeding)

          -  Patients with significantly diseased or obstructed gastrointestinal tract,
             malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral
             medications

          -  Patients who are severely underweight (body mass index [BMI] less than 17) or patients
             with a body surface area (BSA) < 1.4 m^2 as calculated per Dubois 1916 or Mosteller
             1987

          -  Uncontrolled brain metastases or leptomeningeal involvement; patients with brain
             metastases are permitted if they have received appropriate therapy and demonstrated
             control of the brain metastases or leptomeningeal disease following therapy; patients
             with known brain metastases will require magnetic resonance imaging (MRI) brain to
             demonstrate disease control prior to enrollment (lack of symptom progression for two
             weeks off therapeutic doses of steroids, excluding chronic steroids used for control
             of chronic obstructive pulmonary disease [COPD])

          -  Prior cancer diagnosis is allowed if patient is disease-free for >= 3 years, or
             disease free for < 3 years for treated basal cell/ squamous cell skin cancer or in
             situ cervical cancer