Selinexor in Combination With Irinotecan in Adenocarcinoma of Stomach and Distal Esophagus

NCT ID: NCT02283359

Last Updated: 2016-01-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2016-01-31

Brief Summary

The main purpose of this study is to see whether the combination of selinexor (KPT-330) and irinotecan can help people with esophageal or stomach cancer. Researchers also want to find out if the combination of selinexor (KPT-330) and irinotecan is safe and tolerable.

Detailed Description

This is an open label, single group, non-randomized, phase I study with cohort expansion that utilizes the standard 3+3 design for dose. The dose of selinexor will be escalated in combination with the standard doses of irinotecan. The maximum tolerated dose (MTD) for study is defined as the highest dose level at which 1 or less of 6 patients experience a dose limiting toxicity DLT.

Once the MTD is reached and/or the recommended dose for expansion is determined, an additional cohort of 15 patients with advanced gastric or esophageal cancer will be accrued to better define the safety and tolerability of the combination regimen.

Conditions

Esophageal Cancer; Gastric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Selinexor in Combination with Irinotecan

The first study drug is called selinexor (KPT-330). This drug is taken by mouth on days 1, 3, 8 and 10 of each cycle. The starting dose of selinexor will be dependent on the cohort in which the patient is enrolled into. Level -1: 25 mg/m^2; Level 1: 40 mg/m^2; Level 2: 50 mg/m^2; Level 3: 65 mg/m^2.

The second drug is called irinotecan. This drug is given as intravenous (IV) infusion on days 1 and 8 of each cycle. Participants will receive the standard recommended dose: 125 mg/m^2.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

Selinexor is a potent slowly reversible covalent Selective Inhibitor of Nuclear Export (SINE) that specifically blocks the karyopherin protein Exportin 1 or XPO1.

Irinotecan

Intervention Type: DRUG

Irinotecan is a topoisomerase inhibitor and is approved by FDA to treat colorectal cancer. It is administered intravenously.

Interventions

Selinexor

Selinexor is a potent slowly reversible covalent Selective Inhibitor of Nuclear Export (SINE) that specifically blocks the karyopherin protein Exportin 1 or XPO1.

Intervention Type: DRUG

Irinotecan

Irinotecan is a topoisomerase inhibitor and is approved by FDA to treat colorectal cancer. It is administered intravenously.

Intervention Type: DRUG

Other Intervention Names

KPT-330; Camptosar

Eligibility Criteria

Inclusion Criteria

• Must have histologically confirmed gastric, gastro-esophageal junction or distal esophageal adenocarcinoma (predominant histology) that is recurrent, metastatic or unresectable
• Must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1
• Must have received at least one line but less than three lines of prior systemic therapies and have either progressed or intolerant to prior therapies. Patients who have received adjuvant/neoadjuvant therapy within last one year will be eligible as well.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Life expectancy of greater than 3 months
• Must have normal organ and marrow function
• Women of child-bearing potential (WOCBP) must agree to use dual methods of contraception and have a negative serum pregnancy test at screening. Male participants must use an effective barrier method of contraception if sexually active with a WOCBP. For both male and female participants, effective methods of contraception must be used throughout the study and for three months following the last dose.
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Have had chemotherapy, biologic therapy or radiotherapy within 3 weeks prior to entering the study
• Are receiving any other investigational agents for anti-cancer treatment within 3 weeks of starting study medication
• Symptomatic central nervous system (CNS) metastases
• Progression on irinotecan containing regimen
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan
• Major surgery within 2 weeks before cycle 1 Day 1 (C1D1)
• Unstable cardiovascular function
• Patients who are pregnant or lactating
• 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 active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen)
• Any underlying condition that would significantly interfere with the absorption of an oral medication
• > Grade 2 peripheral neuropathy at baseline
• Serious psychiatric or medical conditions that could interfere with treatment
• Concurrent therapy with approved or investigational anticancer therapeutic other than steroids
• History of gastrointestinal perforation and/or fistulae within 6 months prior to C1D1
• Use of strong CYP3A4 inducers or inhibitors within 2 weeks of starting study medication

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amit Mahipal, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

Other Identifiers

MCC-17919

Identifier Type: -

Identifier Source: org_study_id