CDK4/6 InhibitorNCT07100054
Pharmacogenomic and Circulating Biomarkers for CDK4/6 Inhibitors
An observational study of CDK4/6 Inhibitor and Breast Cancer, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- CDK4/6 Inhibitor, Breast Cancer, CYP3A4 Protein, Human
- What is being tested?
- Whole gene sequencing, Drug-drug interaction analysis and Biomarker analysis
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- 10 Oct 2025to Sep 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: This observational cohort will consist of female adult cancer patients routinely seen at the London Regional Cancer Program for breast cancer chemotherapy. Patients must be starting or currently on the CDK4/6 inhibitors abemaciclib, ribociclib and palbociclib for the treatment of breast cancer.
Who may be able to join
- female
- breast cancer diagnosis
- over 18 years of age
- indication for a CDK4/6 inhibitor treatment
- proficient in English
Who cannot join
- None
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Pharmacogenomic and Circulating Biomarkers for Predicting Toxicity or Suboptimal Benefit From Small Molecule Kinase Inhibitor Therapy
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.
Read more
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.
- Conditions
- CDK4/6 Inhibitor, Breast Cancer, CYP3A4 Protein, Human, Drug Interaction, Pharmacogenetic Testing
- Being tested
- Whole gene sequencing, Drug-drug interaction analysis, Biomarker analysis
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Whole gene sequencingGenetic
Whole gene sequencing of CYP3A4 and PXR
Drug-drug interaction analysisOther
Evaluating potential drug interactions with CYP3A4 inhibitors and inducers
Biomarker analysisOther
Determination of circulating CYP3A4 mRNA, and 4b-hydroxycholesterol
What is being measured
The primary outcome is the main question the study is designed to answer.
Predictive model for CDK4/6 inhibitor concentrations
A linear mixed effect model will be applied using CDK4/6 inhibitor levels considering the following independent variables: sex, age, body surface area, height, weight, serum creatinine, drug dose, CYP3A4 and PXR genotype (any impaired-function SNV carrier vs. normal function SNV carrier status/wildtype as per in vitro analysis), CYP3A4 mRNA and 4β-hydroxycholesterol. The model that best describes the fit of CDK4/6 pharmacokinetics will be selected.
Measured: From enrollment to 3 months
Secondary outcomes (2)
Patient reported outcomes
Evaluate the association in patient reported outcomes in the EORTC QLG Core Questionnaire (EORTC QLC-C30) with drug concentrations and/or treatment-related toxicity using common terminology criteria for adverse events (CTCAE). CTCAE is graded on a scale from 1 to 5 with a higher number indicating more toxicity. The EORTC QLC-C30 is a 30-item instrument to assess quality of life. The first 28 items are rated on a scale from 1 to 4 with a higher score indicating worse outcome. The last 2 items are rated on a scale of 1 to 7 with a higher number indicating better health and quality of life.
Measured: From enrollment to 3 months
Patient reported outcomes
Evaluate the association in patient reported outcomes using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-BR42) with drug concentrations and/or treatment-related toxicity using common terminology criteria for adverse events (CTCAE). The CTCAE is graded on a scale from 1 to 5 with a higher number indicating more toxicity. The QLQ-BR42 is a 42 item scale rated from 1 to 4 with a higher number indicating a worse outcome.
Measured: From enrollment to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2025
- Study start10 Oct 2025
- Primary completionSep 2028 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CDK4/6 InhibitorStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard Kim, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07100054
- Sponsor's protocol ID
- P.CTP.1262
- Status last verified
- Dec 2025
- First submitted
- 8 Jul 2025
- Last updated
- 12 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenomic and Circulating Biomarkers for Predicting Toxicity or Suboptimal Benefit From Small Molecule Kinase Inhibitor Therapy
- ClinicalTrials.gov ID
- NCT07100054
- Acronym / sponsor ID
- P.CTP.1262
- Conditions
- CDK4/6 Inhibitor, Breast Cancer, CYP3A4 Protein, Human, Drug Interaction, Pharmacogenetic Testing
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- 10 Oct 2025 (actual)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2028 (estimated)
- First posted
- 1 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- This observational cohort will consist of female adult cancer patients routinely seen at the London Regional Cancer Program for breast cancer chemotherapy. Patients must be starting or currently on the CDK4/6 inhibitors abemaciclib, ribociclib and palbociclib for the treatment of breast cancer.
Key inclusion criteria (5 listed)
- female
- breast cancer diagnosis
- over 18 years of age
- indication for a CDK4/6 inhibitor treatment
- proficient in English
Key exclusion criteria (1 listed)
- None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Whole gene sequencingWhole gene sequencing of CYP3A4 and PXR | Genetic | – |
| Drug-drug interaction analysisEvaluating potential drug interactions with CYP3A4 inhibitors and inducers | Other | – |
| Biomarker analysisDetermination of circulating CYP3A4 mRNA, and 4b-hydroxycholesterol | Other | – |
Primary outcome
Predictive model for CDK4/6 inhibitor concentrations
Time frame: From enrollment to 3 months
A linear mixed effect model will be applied using CDK4/6 inhibitor levels considering the following independent variables: sex, age, body surface area, height, weight, serum creatinine, drug dose, CYP3A4 and PXR genotype (any impaired-function SNV carrier vs. normal function SNV carrier status/wildtype as per in vitro analysis), CYP3A4 mRNA and 4β-hydroxycholesterol. The model that best describes the fit of CDK4/6 pharmacokinetics will be selected.
2 secondary outcomes
Patient reported outcomes
Time frame: From enrollment to 3 months
Patient reported outcomes
Time frame: From enrollment to 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2025.
- Individual participant dataSharing planned: No
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RecruitingPhase 3
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RecruitingPhase 2
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of CDK4/6 Inhibitor and Breast Cancer, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
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 5 inclusion and 1 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: enrolling by invitation, as of the sponsor's last update on 12 Dec 2025. 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 Canada. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Predictive model for CDK4/6 inhibitor concentrations (time frame: From enrollment to 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Dec 2025.