KPT-330 to Treat Poorly Differentiated Lung and Gastroenteropancreatic Tumors

Inclusion Criteria:

• Written informed consent in accordance with federal, local, and institutional guidelines
• Age ≥18 years

• Patients must have a tissue diagnosis of any of the following:

  • Small cell lung cancer (SCLC) or poorly differentiated gastroenteropancreatic neuroendocrine tumor (GEP-NET)
  • Poorly differentiated metastatic neuroendocrine tumors of unknown primary origin
• Measurable disease: Any primary and/or metastatic mass reproducibly measurable in one or two diameters by RECIST 1.1 parameters by cat scan (CT) scan.
• Objective evidence of tumor progression within 4 months prior to study entry, as defined by serial cat scan (CT) per RECIST 1.1 criteria. (At least a 20% increase in the sum of diameters of target lesions. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression).
• Patients must have received at least one prior line of chemotherapy and must have exhausted any other standard-of-care treatment option.
• Prior radiation and surgery is allowed. At least 3 weeks should have elapsed from surgery, chemotherapy, hepatic embolization/ chemoembolization or radioactive isotopes (i.e. Yttrium 90). In any case, disease progression must be documented after treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Concomitant octreotide treatment for carcinoid syndrome is allowed for patients whose tumor has progressed while on octreotide. Patients must have been on a stable dose of octreotide two weeks prior to enrollment and must remain on a stable dose during the study.

• Hematological function:

  • Total white blood cell count (WBC) > 2,000/mm³
  • Absolute neutrophil (ANC) > 1,000/mm³
  • Platelet >100,000mm³
• Adequate hepatic function within 14 days prior to C1D1: total direct bilirubin <2 times the upper limit of normal (ULN; 1.0 mg/dL) and alanine aminotransferase (ALT) <2.5 times ULN (30 U/L). In the case of known (radiological and/or biopsy documented) liver metastasis, ALT <5.0 times ULN is acceptable.
• Adequate renal function within 7 days prior to C1D1: estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockcroft and Gault: (140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female.
• Blood electrolytes should be within the following normal limits:

Bicarbonate (total) 18-30 mEq/L Sodium 135-147 mEq/L Potassium 3.5-5.5 mEq/L Phosphorus 1.8-2.3 mEq/L Magnesium 1.5-3.0 mEq/L Chloride 98-106 mEq/L Calcium (total) 4.5-5.5 mEq/L

• Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and 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.

Exclusion Criteria:

• Patients who are pregnant or lactating
• Patients with the following tumor types: lung carcinoid, pheochromocytomas, paragangliomas, medullary thyroid carcinomas, any other tumors with neuroendocrine features not listed in the inclusion criteria
• Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤3 weeks prior to C1D1
• Major surgery ≤3 weeks prior to C1D1

• Unstable cardiovascular function:

  • Congestive heart failure (CHF) of NYHA Class ≥3 OR
  • Myocardial infarction (MI) within 3 months
• 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 HBsAg (HBV surface antigen)
• Any underlying condition that would significantly interfere with the absorption of an oral medication
• Patients who have active central nervous system (CNS) malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months. Patient with malignant cells in their cerebrospinal fluid (CSF) without CNS symptom may be included.
• Serious psychiatric or medical conditions that could interfere with treatment
• Patients with coagulation problems and active bleeding in the last month (peptic ulcer, epistaxis, spontaneous bleeding)
• Patients with signs of gastrointestinal obstruction or uncontrolled vomiting or diarrhea (>3 episodes/week) with electrolyte abnormalities
• Concurrent therapy with approved or investigational anticancer therapeutic agents other than glucocorticoids
• Participation in an investigational anti-cancer study within 3 weeks prior to cycle 1 day 1