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

Primary Purpose

Esophageal Cancer, Gastric Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Selinexor
Irinotecan
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring Distal Esophagus, Esophageal, Gastric, Carcinoma, Adenocarcinoma, Stomach, Gastro-esophageal junction, Recurrent, Metastatic, Unresectable

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • H. Lee Moffitt Cancer Center and Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Selinexor in Combination with Irinotecan

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Progression Free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Objective Response Rate (ORR)
Only those participants who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Best Overall Response
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response will be evaluated using RECIST guideline V 1.1. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
Overall Survival (OS)
Overall Survival is defined as the time period from start of treatment to death.

Full Information

First Posted
November 3, 2014
Last Updated
January 14, 2016
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02283359
Brief Title
Selinexor in Combination With Irinotecan in Adenocarcinoma of Stomach and Distal Esophagus
Official Title
An Investigator Sponsored Phase 1a/1b Trial of Selinexor in Combination With Irinotecan in Patients With Adenocarcinoma of Stomach and Distal Esophagus
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Terminated
Why Stopped
Principal Investigator left the institution
Study Start Date
December 2014 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Cancer, Gastric Cancer
Keywords
Distal Esophagus, Esophageal, Gastric, Carcinoma, Adenocarcinoma, Stomach, Gastro-esophageal junction, Recurrent, Metastatic, Unresectable

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Selinexor in Combination with Irinotecan
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Selinexor
Other Intervention Name(s)
KPT-330
Intervention Description
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
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Camptosar
Intervention Description
Irinotecan is a topoisomerase inhibitor and is approved by FDA to treat colorectal cancer. It is administered intravenously.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
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).
Time Frame
Up to 18 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Time Frame
Up to 18 months
Title
Objective Response Rate (ORR)
Description
Only those participants who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame
Up to 18 months
Title
Best Overall Response
Description
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response will be evaluated using RECIST guideline V 1.1. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
Time Frame
Up to 18 months
Title
Overall Survival (OS)
Description
Overall Survival is defined as the time period from start of treatment to death.
Time Frame
Up to 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amit Mahipal, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States

12. IPD Sharing Statement

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

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