Selinexor in Treating Patients With Relapsed Small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of single agent selinexor as measured by progression free
survival (PFS) in patients with relapsed chemotherapy-sensitive small cell lung cancer.

SECONDARY OBJECTIVES:

I. To evaluate the objective tumor response rate and disease control rate as determined by
radiographic response.

II. To evaluate the overall survival (OS) in patients with relapsed small cell lung cancer.

III. To evaluate safety and tolerability of single agent selinexor in these patient
populations.

IV. Comparison between each patient's time to progression (TTP) on selinexor with the TTP of
his/her previous therapy(ies).

V. To evaluate correlative endpoints including tumor biopsy and analysis of secreted
factors, leukocyte ribonucleic acid (RNA) analysis.

TERTIARY OBJECTIVES:

I. Analysis of secreted factors (nerve growth factor [NGF], brain-derived neurotrophic
factor [BDNF]).

II. Tumor biopsy (baseline and cycle 2).

OUTLINE:

Patients receive selinexor orally (PO) twice weekly. Courses repeat every 21 days in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up monthly for 3 months, every 3
months for 1 year, and then every 6 months thereafter.

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