Clinical trial NCT02250885: KPT-330 to Treat Poorly Differentiated Lung and Gastroenteropancreatic Tumors
Official title: Investigator Initiated, Phase 2 Clinical Trial of Selinexor (KPT-330) for the Treatment of Poorly Differentiated Lung and Gastroenteropancreatic Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Neuroendocrine
Keywords: Selinexor
phase 2
Gabrail
Lead sponsor: Gabrail Cancer Center Research
Sponsor class: OTHER
Collaborators: name: Karyopharm Therapeutics Inc
First posted: 2014-09-26
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Evaluate the efficacy of Selinexor in patients with poorly differentiated lung and gastrointestinal and pancreatic neuroendocrine tumors.

Detailed description: Evaluate the efficacy of Selinexor in patients with poorly differentiated lung and gastrointestinal and pancreatic neuroendocrine tumors in adult patients age \>/= to 18.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate
timeFrame: Every 8 weeks from screening until documented disease progression or date of death, whichever occurs first, up to approximately 100 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
Study officials:
affiliation: Gabrail Cancer Center Research
name: Nashat Y Gabrail, MD
role: PRINCIPAL_INVESTIGATOR
References: