Improving the Safety of Fluoropyrimidine-based Chemotherapy

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

1440 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-15

Study Completion Date

2021-01-31

Brief Summary

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In this study it will be determined whether the rate of severe toxicity associated with fluoropyrimidine treatment (capecitabine or 5-fluorouracil) can be significantly diminished by individualized dosing of fluoropyrimidines based on upfront phenotypic assessment of dihydropyrimidine dehydrogenase (DPD) deficiency.

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Detailed Description

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In this study a phenotypic approach will be studied to determine the additional value of pretreatment uracil level-guided dose individualization in wildtype patients. Patients with a pretreatment serum uracil concentration above 16 ng/ml will be treated with a 50% reduced fluoropyrimidine starting dose. The pretreatment serum uracil levels in DPYD variant carriers will be assessed retrospectively and non-interventional. Additionally, the effect of a higher dose reduction in c.1236G\>A and c.2846A\>T DPYD variants carriers (50% instead of 25%) will be studied.

Conditions

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Neoplasms

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Wild type for DPYD

Patients screened for four single nucleotide polymorphisms (SNPs) in DPYD (DPYD\*2A, c.2846A\>T, c.1236G\>A/HapB3 and DPYD\*13) that are found to be wild type for these SNPs

Group Type EXPERIMENTAL

Fluoropyrimidine (capecitabine or 5-fluorouracil)

Intervention Type DRUG

Patients that are found to be wild type and have a pre-treatment uracil concentration above 16 ng/mL will receive a reduced dosage of capecitabine or 5-fluorouracil (50% reduction). The dose will be titrated after 2 cycles , to achieve maximal safe exposure. Patients that are wildtype with a uracil concentration below 16 ng/mL will receive a normal (full) dose.

heterozygous carrier of c.1236G>A or c.2846A>T DPYD variant

Patients screened for four single nucleotide polymorphisms (SNPs) in DPYD (DPYD\*2A, c.2846A\>T, c.1236G\>A/HapB3 and DPYD\*13) that are found to be heterozygous for c.1236G\>A or c.2846A\>T of these SNPs

Group Type EXPERIMENTAL

Fluoropyrimidine (capecitabine or 5-fluorouracil)

Intervention Type DRUG

Patients that are heterozygous carriers of c.1236G\>A or c.2846A\>T DPYD variant will receive a reduced dosage of capecitabine or 5-FU (50 % reduction). The dose will be titrated after 2 cycles, to achieve maximal safe exposure.

Homozygous or compound heterozygous carrier of DPYD variants

Patients screened for four single nucleotide polymorphisms (SNPs) in DPYD (DPYD\*2A, c.2846A\>T, c.1236G\>A/HapB3 and DPYD\*13) that are found to be homozygous or compound heterozygous for these SNPs

Group Type EXPERIMENTAL

Fluoropyrimidine (capecitabine or 5-fluorouracil)

Intervention Type DRUG

Patients with homozygous or compound heterozygous DPYD variants will be treated with a reduced dose of capecitabine or 5-FU based on the DPD enzyme activity measured in peripheral blood mononuclear cells.

Interventions

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Fluoropyrimidine (capecitabine or 5-fluorouracil)

Patients that are found to be wild type and have a pre-treatment uracil concentration above 16 ng/mL will receive a reduced dosage of capecitabine or 5-fluorouracil (50% reduction). The dose will be titrated after 2 cycles , to achieve maximal safe exposure. Patients that are wildtype with a uracil concentration below 16 ng/mL will receive a normal (full) dose.

Intervention Type DRUG

Fluoropyrimidine (capecitabine or 5-fluorouracil)

Patients that are heterozygous carriers of c.1236G\>A or c.2846A\>T DPYD variant will receive a reduced dosage of capecitabine or 5-FU (50 % reduction). The dose will be titrated after 2 cycles, to achieve maximal safe exposure.

Intervention Type DRUG

Fluoropyrimidine (capecitabine or 5-fluorouracil)

Patients with homozygous or compound heterozygous DPYD variants will be treated with a reduced dose of capecitabine or 5-FU based on the DPD enzyme activity measured in peripheral blood mononuclear cells.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Pathologically confirmed malignancy for which treatment with a fluoropyrimidine is considered to be in the patient's best interest
2. Patient need to be of Western descent
3. Age ≥ 18
4. Able and willing to give written informed consent
5. WHO performance status of 0, 1 or 2
6. Able and willing to undergo extra blood sampling for study related analysis
7. Adequate baseline patient characteristics, in the opinion of the treating physician (complete blood count, hepatic function which involves serum bilirubin, AST, ALT, and renal function)

Exclusion Criteria

1. Prior treatment with fluoropyrimidines
2. Patients with known substance abuse, psychotic disorders, and/or other diseases expected to interfere with study or the patient's safety in the opinion of the treating physician
3. Patients treated with the combination of a fluoropyrimidine and irinotecan

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No