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

NCT02283359 | Terminated Phase 1

• 1 other identifier: MCC-17919
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Cancer; Gastric Cancer

Keywords

Distal Esophagus; Esophageal; Gastric; Carcinoma; Adenocarcinoma; Stomach; Gastro-esophageal junction; Recurrent; Metastatic; Unresectable

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  The MTD for study is defined as the highest dose level at which 1 or less of 6 patients experience a dose limiting toxicity (DLT).

  Up to 18 months

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  Up to 18 months

• Objective Response Rate (ORR)

  Up to 18 months

• Best Overall Response

  Up to 18 months

• Overall Survival (OS)

  Up to 18 months

Study Arms (1)

Selinexor in Combination with Irinotecan

EXPERIMENTAL

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.

Drug: Selinexor; Drug: Irinotecan

Interventions

Selinexor DRUG

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

Also known as: KPT-330

Selinexor in Combination with Irinotecan

Irinotecan DRUG

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

Also known as: Camptosar

Selinexor in Combination with Irinotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Carcinoma; Adenocarcinoma; Recurrence; Neoplasm Metastasis

Interventions

selinexor; Irinotecan

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Amit Mahipal, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2014
• First Posted: November 5, 2014
• Study Start: December 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2016
• Last Updated: January 15, 2016

Record last verified: 2016-01

Locations

US (1)