Safety, Tolerability and Pharmacokinetics of Oral Tablet of Irinotecan in Adult Patients With Solid Tumors

October 1, 2020 updated by: Dorte Nielsen

Irinotecan Gastro-resistant Tablet. An Open Label Phase I, Dose Escalating Study Evaluating Safety, Tolerability and Pharmacokinetics of Oral Administration of Irinotecan in Adult Patients With Solid Tumors

This study evaluates the safety, tolerability and pharmacokinetics of oral administration of irinotecan in adult patients. Oral irinotecan will be administered as monotherapy in a dose escalation trial to establish the Maximal Tolerated Dose. Totally 25 patients will be treated with irinotecan tablets as mono-therapy. As an extension trial 12 patients will be treated with oral irinotecan in combination with oral capecitabine

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study is a phase I, open-label, dose escalation single center study in patients with solid tumors. The study will investigate safety, tolerability and Maximal Tolerated Dose as primary end-points of an irinotecan tablet given as single agent or in combination with oral capecitabine. Secondary end-points are pharmacokinetics and preliminary anti-tumor response.

Cohorts of 3 patients will be treated on selected dose level with oral irinotecan in order to identify Dose Limiting Toxicity (DLT) and Maximal Tolerated Dose (MTD). Totally 12 subjects will be treated at the MTD level. Patients will receive irinotecan tablets once daily in the morning for 14 consecutive days within 3 week treatment cycles. As an extension trial totally 12 subjects will be treated with oral irinotecan in combination with oral capecitabine. Patients treated in combination therapy will receive irinotecan tablets once daily in the morning for 14 consecutive days in combination with capecitabine dosed twice daily for 14 consecutive days within 3 week treatment cycles.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
39

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Herlev, Denmark, 2730
        • Herlev Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Signed written Informed Consent
  • 18 years of age or older
  • Capable of understanding the protocol requirements and risk associated with the study
  • Patients must have histological confirmed malignancy (solid tumor) that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
  • Patients with either measurable disease according to RECIST 1.1 or non-measurable disease
  • Performance status 0-1 (ECOG)
  • Life expectancy ≥ 3 months
  • Coagulation INR < 1.3 and APTT within normal limits
  • WBC ≥ 3000/mm3
  • Absolute neutrophil count ≥ 1500/mm3
  • Hemoglobin ≥ 6.0 mmol/L
  • Platelet count ≥ 100.000/mm3
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN AST and ALT ≤ 2.5 times ULN. For patients with liver metastasis adequate hepatic function is defined by aspartate aminotransferase (AST) ≤ 5 x ULN and alanine aminotransferase ALT ≤ 5 x ULN
  • No severe or uncontrolled renal condition (creatinine ≤ than 1.5 ULN)
  • No significant cardiovascular disease (New York Heart Association Class III and IV)
  • No other severe cardiac condition not defined above
  • No significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year prior for patients to be enrolled and treated in combination with oral capecitabine
  • No severe or uncontrolled pulmonary condition
  • No known prior hypersensitivity reaction to irinotecan
  • No known prior hypersensitivity to capecitabine or 5-fluorouracil for patients to be enrolled and treated in combination with oral capecitabine
  • No chronic enteropathy (e.g. active inflammatory bowel disease, extensive intestinal resection or chronic diarrhea)
  • No bowel obstruction or sub-obstruction
  • No prior history of intestinal malabsorption
  • Patients have to be able to swallow normally and have to be willing to comply with the intake of tablets
  • No psychiatric condition that would preclude study participation
  • No co-existing active infection requiring antibiotics or any co-existing medical conditions likely to interfere with study procedures
  • No other condition that will preclude study participation
  • A negative pregnancy test for women of childbearing potential. For men and women of child-producing potential, the use of effective contraceptives methods during the study and at least 3 months after discontinuations of the study drug is required.
  • Not pregnant or nursing
  • Peripheral neuropathy NCI CTCAE grade less than 2 for patients to be enrolled and treated in combination with oral capecitabine
  • The patient is willing and able to comply with hospitalization for treatment and scheduled follow-up visits and examinations

Exclusion Criteria:

  • Simultaneous participation in any other study involving investigational drugs or having participated in a study within 4 weeks prior to start of study treatment
  • Symptomatic brain metastases
  • Intake of any prohibited concomitant medication
  • Known Dihydropyrimidine dehydrogenase (DPD) deficiency for patients to be enrolled and treated in combination with oral capecitabine.

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Irinotecan
Dose escalation study in cohorts of minimum 3 patients of an Irinotecan tablet taken once daily for 14 days within 3 week treatment cycle
Drug: Irinotecan
Dose Escalation
Experimental: Irinotecan with Capecitabine
Dose escalation study in cohorts of minimum 3 patients of an Irinotecan tablet taken once daily in combination with Capecitabine tablet taken twice daily for 14 days within 3 week treatment cycle
Drug: Irinotecan
Dose Escalation
Drug: Capecitabine
Dose Escalation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximal Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of oral Irinotecan based on incidence of Treatment-Emergent Adverse Events
Time Frame: 2 treatment cycles of 3 weeks
Number of patients with Treatment Related Adverse Events as assessed according to the NCI Common Terminology Criteria for Adverse events CTCAE version 4.0
2 treatment cycles of 3 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) and the Dose Limiting Toxicity (DLT) of oral Irinotecan in combination with oral Capecitabine based on incidence of Treatment-Emergent Adverse Events
Time Frame: 2 treatment cycles of 3 weeks
Number of patients with Treatment Related Adverse Events as assessed according to the NCI Common Terminology Criteria for Adverse events CTCAE version 4.0
2 treatment cycles of 3 weeks
Area under the Concentration-Time-Curve (AUC) for Irinotecan and its metabolites SN-38 and SN-38 glucoronide
Time Frame: Day 1 and Day 14 of first 3 weeks treatment cycle
PK samples will be collected at predetermined time intervals and pharmacokinetic parameter calculated and reported based on the plasma concentration profile
Day 1 and Day 14 of first 3 weeks treatment cycle
Maximum Serum Concentration (Cmax) for irinotecan and its metabolites SN-38 and SN-38 glucoronide
Time Frame: Day 1 and Day 14 of first 3 weeks treatment cycle
PK samples will be collected at predetermined time intervals and pharmacokinetic parameter calculated and reported based on the plasma concentration profile
Day 1 and Day 14 of first 3 weeks treatment cycle
Time to Maximum Serum Concentration (Tmax) for irinotecan and its metabolites SN-38 and SN-38 glucoronide
Time Frame: Day 1 and Day 14 of first 3 weeks treatment cycle
PK samples will be collected at predetermined time intervals and pharmacokinetic parameter calculated and reported based on the plasma concentration profile
Day 1 and Day 14 of first 3 weeks treatment cycle
Half-life (t½) for irinotecan and its metabolites SN-38 and SN-38 glucoronide
Time Frame: Day 1 and Day 14 of first 3 weeks treatment cycle
PK samples will be collected at predetermined time intervals and pharmacokinetic parameter calculated and reported based on the plasma concentration profile
Day 1 and Day 14 of first 3 weeks treatment cycle
Serum concentration 24 hours after dosing and prior to administration of the next dose (C24) for Irinotecan and its metabolites SN-38 and SN-38 glucoronide
Time Frame: Day 1 and Day 14 of first 3 weeks treatment cycle
PK samples will be collected at predetermined time intervals and pharmacokinetic parameter calculated and reported based on the plasma concentration profile
Day 1 and Day 14 of first 3 weeks treatment cycle
Objective tumor response to treatment based on RECIST 1.1 criteria
Time Frame: 2 treatment cycles of 3 weeks
CT scans with tumor response as assessed using RECIST 1.1. criteria
2 treatment cycles of 3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dorte Nielsen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Benny Vittrup, Herlev Hospital, Department of Oncology, Denmark

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 15, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 3, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 11, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 26, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 27, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 5, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 1, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AA1446

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metastatic Colorectal Cancer

Clinical Trials on Irinotecan

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings