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

NCT03295084 | Completed Phase 1 DMC

• 1 other identifier: AA1446
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief 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. As an extension trial 12 patients will be treated with oral irinotecan in combination with oral capecitabine

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (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

  2 treatment cycles of 3 weeks

Secondary Outcomes (7)

• 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

  2 treatment cycles of 3 weeks

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

  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

  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

  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

  Day 1 and Day 14 of first 3 weeks treatment cycle

Study Arms (2)

Irinotecan

EXPERIMENTAL

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

Irinotecan with Capecitabine

EXPERIMENTAL

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; Drug: Capecitabine

Interventions

Irinotecan DRUG

Dose Escalation

Irinotecan; Irinotecan with Capecitabine

Capecitabine DRUG

Dose Escalation

Irinotecan with Capecitabine

Eligibility Criteria

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

You may qualify if:

• Signed written Informed Consent
• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dorte Nielsen: lead

Study Sites (1)

Herlev Hospital

Herlev, 2730, Denmark

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Benny Vittrup

  Herlev Hospital, Department of Oncology, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD, DMSci

Model Details: 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)

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 27, 2017
• Study Start: July 15, 2015
• Primary Completion: July 3, 2018
• Study Completion: October 30, 2018
• Last Updated: October 5, 2020

Record last verified: 2020-10

Locations

DK (1)