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Metastatic Colorectal CancerPhase 1NCT03295084

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

A Phase 1 study testing Irinotecan and Capecitabine in people with Metastatic Colorectal Cancer, run by Dorte Nielsen at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Irinotecan and Capecitabine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
1 siteDenmark
Study dates
15 Jul 2015to 30 Oct 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 32Show fewer
  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Herlev Hospital

    Herlev, 2730

Other trials in Denmark

About this study

Official title: 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

Read the 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.

Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03295084
Study groupRoleWhat they receive
IrinotecanExperimentalDose escalation study in cohorts of minimum 3 patients of an Irinotecan tablet taken once daily for 14 days within 3 week treatment cycle
Receives: Drug: Irinotecan
Irinotecan with CapecitabineExperimentalDose 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
Receives: Drug: Irinotecan; Drug: Capecitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximal Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of oral Irinotecan based on incidence of Treatment-Emergent Adverse Events

    Number of patients with Treatment Related Adverse Events as assessed according to the NCI Common Terminology Criteria for Adverse events CTCAE version 4.0

    Measured: 2 treatment cycles of 3 weeks

Secondary outcomes (7)

  1. 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

    Number of patients with Treatment Related Adverse Events as assessed according to the NCI Common Terminology Criteria for Adverse events CTCAE version 4.0

    Measured: 2 treatment cycles of 3 weeks

  2. Area under the Concentration-Time-Curve (AUC) for Irinotecan and its metabolites SN-38 and SN-38 glucoronide

    PK samples will be collected at predetermined time intervals and pharmacokinetic parameter calculated and reported based on the plasma concentration profile

    Measured: Day 1 and Day 14 of first 3 weeks treatment cycle

  3. Maximum Serum Concentration (Cmax) for irinotecan and its metabolites SN-38 and SN-38 glucoronide

    PK samples will be collected at predetermined time intervals and pharmacokinetic parameter calculated and reported based on the plasma concentration profile

    Measured: Day 1 and Day 14 of first 3 weeks treatment cycle

  4. Time to Maximum Serum Concentration (Tmax) for irinotecan and its metabolites SN-38 and SN-38 glucoronide

    PK samples will be collected at predetermined time intervals and pharmacokinetic parameter calculated and reported based on the plasma concentration profile

    Measured: Day 1 and Day 14 of first 3 weeks treatment cycle

  5. Half-life (t½) for irinotecan and its metabolites SN-38 and SN-38 glucoronide

    PK samples will be collected at predetermined time intervals and pharmacokinetic parameter calculated and reported based on the plasma concentration profile

    Measured: Day 1 and Day 14 of first 3 weeks treatment cycle

  6. 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

    PK samples will be collected at predetermined time intervals and pharmacokinetic parameter calculated and reported based on the plasma concentration profile

    Measured: Day 1 and Day 14 of first 3 weeks treatment cycle

  7. Objective tumor response to treatment based on RECIST 1.1 criteria

    CT scans with tumor response as assessed using RECIST 1.1. criteria

    Measured: 2 treatment cycles of 3 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2017
  2. Study start15 Jul 2015
  3. Primary completion3 Jul 2018
  4. Study completion30 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Open labelled study with enrollment in the order of confirmation of eligibility. Escalating doses of study drug in sequential patient cohorts for identification of DLT and MTD (Phase 1)
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03295084
Sponsor's protocol ID
AA1446
Status last verified
Oct 2020
First submitted
11 Sep 2017
Last updated
5 Oct 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Irinotecan and Capecitabine in people with Metastatic Colorectal Cancer, run by Dorte Nielsen at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03295084.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2020.

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