Personalized dosing of FOLFIRINOX in pancreatic cancer patients: a phase-2 pharmacokinetic, safety and feasibility trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Catharina Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Neoplasms [C04]

Trial duration

18 Sep 2024 → ongoing

Decision date (initial)

2024-07-09

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-510576-21-00

WHO UTN

U1111-1301-8896

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Others, Safety, Therapy

PART A: To validate the population AUC0-46h range of intravenous 5-FU in patients with pancreatic cancer treated with BSA-dosed FOLFIRINOX, and to determine the percentage of these patients that achieves therapeutic exposure (AUC) range of 5-FU, defined as an AUC0-46h target range of 5-FU between 20 and 30 mg*h/L.
PART B: To determine the safety, model performance and feasibility of MIPD of 5-FU in pancreatic cancer patients treated with FOLFIRINOX.

Secondary objectives 13

1. To develop a population PK model of 5-FU for applying 5-FU MIPD in for patients treated with FOLFIRINOX
2. To identify patient and treatment characteristics correlated with 5-FU exposure/PK (variability) and 5-FU induced toxicity
3. To determine the intra-individual and inter-individual variation in 5- FU AUC0-46
4. To determine the incidence of grade 1-5 toxicity, toxicity-related hospital admissions, treatment delay and early treatment withdrawal at 5-FU exposure below, within and above the target window.
5. To determine efficacy outcomes at 5-FU exposure below, within and above the target window, accounted for stage of disease
6. To determine the percentage of patients that achieves therapeutic (AUC) range of 5-FU defined by an AUC target of 5-FU AUC0-46h between 20 and 30 mg*h/L when dosed based on 5-FU MIPD
7. To get insights in the preliminary clinical benefit (ORR, OS, PFS) of 5-FU MIPD, accounted for stage of disease
8. To determine the feasibility/turn-around-time of 5-FU model-informed precision dosing defined as no delay of treatment due to 5-FU MIPD
9. To verify the use of 5-FU MIPD by treating physicians in clinical practice for 5-FU dosing
10. To determine the population irinotecan, SN-38 and SN-38G exposure (AUC) of intravenous irinotecan in patients with pancreatic cancer treated with FOLFIRINOX
11. To get insights in whether limited sampling of 5-FU samples is sufficient to safely adjust 5-FU dosing in routine clinical practice, and which limited sampling strategy is adequate for use
12. To get insights in the safety and pharmacokinetics of irinotecan dosages in different UGT1A1 genotypes.
13. To get insights the optimal therapeutic 5-FU exposure range (AUC0-46h) in patients pancreatic cancer treated with FOLFIRINOX.

Conditions and MedDRA coding

Pancreatic cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Pathologically confirmed pancreatic cancer diagnosis (for PART B: unresectable locally advanced or metastatic setting)
2. Patient scheduled to start FOLFIRINOX treatment
3. Patient with age ≥ 18
4. Patient is able and willing to give written IFC
5. Patient is able and willing to undergo extra blood sampling for 5-FU analysis
6. WHO performance status 0-2

Exclusion criteria 2

1. Patient with known substance abuse, psychotic disorders, and/or other diseases expected to interfere with study or patient’s safety
2. Patient with DPYD gene-activity score 0 and 0.5

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percentage of patients undergoing FOLFIRINOX treated with standard-dosed (BSA) 5-FU achieving a 5-FU target AUC range (5-FU AUC0-46h between 20 and 30 mg*h/L) within two dose cycles of 5-FU
2. Percentage of patients undergoing FOLFIRINOX treated with 5-FU MIPD achieving a 5-FU target AUC range (5-FU AUC0-46h between 20 and 30 mg*h/L) within two dose cycles of 5-FU

Secondary endpoints 8

1. Incidence of grade ≥ 1-5 toxicity, toxicity-related hospitalization, treatment delay (> 2 days) and early treatment withdrawal in patients treated with FOLFIRINOX
2. Turn-around-time of 5-FU MIPD (or incidence of treatment delay due to 5-FU MIPD)
3. Compliance to 5-FU MIPD dosing advice by treating physicians
4. Pharmacokinetics of 5-FU, FUH2, Irinotecan, SN-38, SN38G and Oxaliplatin
5. Direct medical costs of 5-FU based treatment
6. Disease free surivival, progression free survival, objective response rate and overall survival of patients treated with FOLFIRINOX
7. AUC0-46h of 5-FU in patients treated with FOLFIRINOX
8. Correlation of patient and treatment characteristics with AUC of 5-FU and/or irinotecan and their metabolites

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Catharina Ziekenhuis Stichting

Sponsor organisation

Catharina Ziekenhuis Stichting

Address

Michelangelolaan 2

City

Eindhoven

Postcode

5623 EJ

Country

Netherlands

Scientific contact point

Organisation

Catharina Ziekenhuis Stichting

Contact name

Study-coordinator

Public contact point

Organisation

Catharina Ziekenhuis Stichting

Contact name

Study-coordinator

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications