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Набор по приглашению NCT07100054

Pharmacogenomic and Circulating Biomarkers for CDK4/6 Inhibitors

— Наблюдательное CDK4/6 Inhibitor Breast Cancer CYP3A4 Protein, Human Drug Interaction

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают
В протоколе указаны: Whole gene sequencing, Drug-drug interaction analysis, Biomarker analysis.
Кому может быть актуально
Состояния в реестре: CDK4/6 Inhibitor, Breast Cancer, CYP3A4 Protein, Human, Drug Interaction. Базовые параметры: от 18 лет · Женщины.
Что важно проверить
Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится
Канада
Следующий шаг
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Официальное название

Pharmacogenomic and Circulating Biomarkers for Predicting Toxicity or Suboptimal Benefit From Small Molecule Kinase Inhibitor Therapy

Обзор

The goal of this research study is to reduce adverse effects of anti-cancer medications known as kinase inhibitors, while preserving their therapeutic benefits. There have been major advances in the way cancers are treated. A class of drugs known as kinase inhibitors have proven to be highly effective for the treatment of cancers, including lung, kidney, gastrointestinal, and breast cancers. However, kinase inhibitor medications are well known for having unpredictable side effects. The body breaks down (metabolizes) medications such as kinase inhibitors using an enzyme known as cytochrome P450 3A4 (CYP3A4). CYP3A4 is the most important drug metabolizing enzyme in humans due to the fact that it is involved in the metabolism of nearly half of all prescribed medications and almost all of the currently prescribed kinase inhibitors. Among patients, there can be nearly 400 times difference in how efficiently CYP3A4 metabolizes drugs. Remarkably, very little is known about the role of genetic differences in CYP3A4 and a gene known as pregnane X receptor (PXR). PXR serves as a sensor for drugs in the body and helps to regulate how much CYP3A4 is made. Currently, there are no predictive biomarkers, whether in genes (genomic) or circulating in blood (endogenous) that could aid treating oncologists with regards predicting adverse effects or suboptimal response to this important class of anticancer drugs. The goal is to carry out DNA sequencing for genetic changes in CYP3A4 and PXR to assess differences in enzyme activity of not only common, but also rare genetic variants. CYP3A4 activity will be determined in participants blood samples based on break down products of the drug tamoxifen as well as cholesterol, the latter called 4β-hydroxycholesterol, both known to be influenced by the CYP3A4 enzyme. Since cholesterol is naturally made in the body, comparing blood cholesterol to 4β-hydroxycholesterol levels will be a biomarker of CYP3A4 metabolic activity that can be measured in anyone. Furthermore, circulating CYP3A4 messenger RNA from human blood will be measured as another independent marker of CYP3A4 gene expression. A model will be generated that includes these biomarkers of CYP3A4 expression and function, as well as genetic variation in CYP3A4 and PXR, that will aid in better identifying which patients may be at risk for loss of benefit or toxicity from kinase inhibitor therapy. This model will be evaluated in 100 breast cancer patients undergoing chemotherapy with kinase inhibitors, namely cyclin-dependent kinases CDK4 and CDK6 inhibitor (abemaciclib, ribociclib or palbociclib), as such kinase inhibitors are widely prescribed for breast cancer and are known to be broken down by CYP3A4.

Вмешательства

  • Генная терапия Whole gene sequencing
    Whole gene sequencing of CYP3A4 and PXR
  • Другое Drug-drug interaction analysis
    Evaluating potential drug interactions with CYP3A4 inhibitors and inducers
  • Другое Biomarker analysis
    Determination of circulating CYP3A4 mRNA, and 4b-hydroxycholesterol

Первичные конечные точки

  • Predictive model for CDK4/6 inhibitor concentrations [Срок оценки: From enrollment to 3 months]
Вторичные конечные точки (2)
  • Patient reported outcomes [Срок оценки: From enrollment to 3 months]
  • Patient reported outcomes [Срок оценки: From enrollment to 3 months]

Критерии участия

Критерии включения

  • female
  • breast cancer diagnosis
  • over 18 years of age
  • indication for a CDK4/6 inhibitor treatment
  • proficient in English

Критерии исключения

  • None

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения
Когортное

Центры проведения

Канада · 1 центр
  • London Health Sciences Centre Research Institute — London

Идентификаторы

NCT: NCT07100054 · P.CTP.1262

Первоисточники (государственные реестры)

Открыть это исследование на ClinicalTrials.gov ↗