Completed

A Phase I/II Study of ISIS 183750 in Combination With Irinotecan in Irinotecan-refractory Colorectal Cancer

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What is being tested

ISIS 183750

+ Irinotecan

+ ISIS 183750

Drug
Who is being recruted

Colonic Diseases+8

+ Digestive System Diseases

+ Digestive System Neoplasms

Over 18 Years
+10 Eligibility Criteria
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 1 & 2
Interventional
Study Start: August 2012
See protocol details

Summary

Principal SponsorNational Cancer Institute (NCI)
Last updated: April 25, 2016
Sourced from a government-validated database.Claim as a partner

Study start date: August 1, 2012

Actual date on which the first participant was enrolled.

Background: The eukaryotic translation initiation factor - eIF4E - is a potent oncogene that is found to be dysregulated in approximately 30% of human cancers. Upregulation of eIF4E is an early event in colorectal cancer (CRC) and correlates with CRC progression. ISIS 183750 is a second-generation antisense oligonucleotide (ASO) designed to inhibit the production of the human eukaryotic translation initiation factor 4E (eIF4E) protein. Objectives: Primary: To establish Maximum Tolerated Dose (MTD) and establish safety for the combination of ISIS 183750 and irinotecan in advanced solid tumors. Secondary: To evaluate Response Rate, Progression Free Survival (PFS), Overall Survival (OS) for the combination of ISIS 183750 and irinotecan in advanced irinotecan-refractory colorectal cancer. To perform correlative studies to evaluate the effect of eIF4E inhibition on relevant regulated proteins and immune cells. To characterize the plasma pharmacokinetic (PK) parameters for ISIS 183750 in the absence and presence of irinotecan To characterize the plasma PK parameters for irinotecan in the presence of ISIS 183750 Eligibility: -Adult patients with irinotecan-resistant colorectal cancer (or advanced solid tumor in phase I part). Design: This is a single-arm phase I/II study whereby all patients will receive the combination of ISIS 183750 and irinotecan. All cycles are 28 days. Cycle 1 only: ISIS 183750 will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22. Cycle 2 and beyond: ISIS 183750 will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks. Irinotecan will be administered at a dose of 160mg/m^2 as an intravenous infusion every second week commencing on Day 15 of Cycle 1. The primary endpoint of the study will be to establish maximum tolerated dose (MTD) for the combination of ISIS 183750 and irinotecan in advanced solid tumors. The phase II portion of the study will be confined to irinotecan-refractory colorectal cancer. Irinotecan-refractory will be defined as patients who have radiological evidence of disease progression whilst receiving irinotecan or within 3 months after completing it. Correlative studies will comprise: Mandatory pre- and post- dose biopsies for eIF4e messenger ribonucleic acid (mRNA) and protein (IHC) analysis will be performed in the phase II portion of the study; Immune subsets; positron emission tomography (PET) responses (only in expansion cohort); Pharmacokinetic data regarding the interaction of irinotecan and ISIS183750 in 10-12 patients.

NCT01675128
Principal SponsorNational Cancer Institute (NCI)
Last updated: April 25, 2016
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details

24 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria

Any sex

Biological sex of participants that are eligible to enroll.

Over 18 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Colonic DiseasesDigestive System DiseasesDigestive System NeoplasmsGastrointestinal DiseasesGastrointestinal NeoplasmsIntestinal DiseasesIntestinal NeoplasmsNeoplasmsNeoplasms by SiteRectal DiseasesColorectal Neoplasms

Criteria

10 exclusion criteria prevent from participating
Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy are excluded from this study due to the possibility of pharmacokinetic interactions between antiretroviral medications and the investigational agent
Known hepatitis B or hepatitis C infection
Patients may not be receiving any antineoplastics or other drugs intended to treat cancer within 4 weeks prior to starting ISIS 183750
Patients who have had chemotherapy (or so-called targeted systemic therapy), large field radiotherapy, or major surgery must wait 4 weeks after completing treatment prior to entering the study
Show More Criteria

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives

3 intervention groups are designated in this study

This study does not include a placebo group 

Treatment Groups

Group I

Experimental
Irinotecan 160 mg/m^2 every other week; ISIS 183750 started 800 mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.

Group II

Experimental
Irinotecan 180 mg/m^2 every other week; ISIS 183750 1000 mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.

Group III

Experimental
Irinotecan 160 mg/m^2 every other week; ISIS 183750 1000mg every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.

Study Objectives

Primary Objectives

Secondary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 1 location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, United StatesOpen National Institutes of Health Clinical Center, 9000 Rockville Pike in Google Maps
CompletedOne Study Center