DiviTum-TKa Assay for Breast Cancer

No longer recruiting at 17 trial locations

Overseen By Nathalie Wiesendanger, MS

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Yale University

Must be taking: CDK4/6 inhibitors

Disqualifiers: Non-metastatic disease, prior CDK4/6 use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a specific test, called DiviTum-TKa, can identify optimal levels of certain cancer medications in the blood for individuals with hormone-positive, HER2-negative breast cancer that has metastasized. The goal is to enhance the effectiveness of these medications and ensure they do not interact poorly with other drugs. Individuals with this type of breast cancer who are beginning treatment with CDK4/6 inhibitors may be suitable candidates for the trial. As an unphased trial, this study offers patients the chance to contribute to innovative research that could improve future treatment strategies.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves starting a new treatment with CDK4/6 inhibitors, it's best to discuss your current medications with the trial team to ensure there are no interactions.

What prior data suggests that the DiviTum-TKa assay is safe for use in breast cancer patients?

Research has shown that the DiviTum-TKa test is a blood test used to assess the effectiveness of treatments for certain breast cancers, particularly hormone receptor-positive metastatic breast cancer. Although specific side effects from the test itself are not detailed, FDA approval confirms its safety. The test measures thymidine kinase activity (TKa), which relates to cancer cell growth. Lower TKa levels might suggest a reduced risk of the cancer worsening shortly after the test. While no specific side effects are noted, FDA approval for monitoring treatment response indicates it is generally safe and well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the DiviTum-TKa assay because it offers a novel way to monitor breast cancer by analyzing specific markers in the blood. Unlike traditional treatments that primarily target the cancer cells directly, DiviTum-TKa measures the activity of an enzyme called thymidine kinase 1 (TK1), which is linked to cancer cell proliferation. This method could provide real-time insights into how well a treatment is working and help tailor therapies more precisely, potentially leading to better outcomes for patients.

What evidence suggests that the DiviTum-TKa assay is effective for optimizing CDK 4/6 inhibitor levels in metastatic breast cancer?

Research shows that the DiviTum-TKa test, which participants in this trial will undergo, can track and predict the response of hormone receptor-positive metastatic breast cancer to treatment. Studies have found that thymidine kinase activity (TKa) below 250 DuA is linked to a lower risk of cancer worsening in the next 30 to 60 days. This test provides crucial insights into cancer behavior. By identifying these levels, the test may enhance the effectiveness of CDK 4/6 inhibitors, common drugs for this cancer type, ensuring they work better and have fewer side effects. This approach also helps verify medication adherence and allows for adjustments to other drugs patients may be using. ^{1 2 4 6 7}

Who Is on the Research Team?

Mariya Rozenblit, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals with ER/PR positive, HER2-negative metastatic breast cancer who are currently receiving CDK 4/6 inhibitors. It aims to optimize medication levels using the DiviTum-TKa test, which measures a biomarker associated with cell growth.

Inclusion Criteria

I have not started CDK4/6 inhibitor therapy yet.

I can take care of myself but may not be able to do heavy physical work.

Willing and able to provide written informed consent for the trial

Exclusion Criteria

My cancer has not spread to other parts of my body.

I have previously used CDK4/6 inhibitor therapy.

I am unable to give informed consent for the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CDK4/6 inhibitors in combination with endocrine therapy, with blood samples collected on days 1, 15, and 28 of cycle 1, days 15 and 28 of cycle 2, days 15 and 28 of cycle 3, and day 28 of subsequent cycles for up to 12 cycles

Up to 12 cycles

Multiple visits per cycle for blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years

What Are the Treatments Tested in This Trial?

Interventions

• DiviTum-TKa

Trial Overview The study tests if the DiviTum-TKa assay can help find the best dose of CDK 4/6 inhibitor medications and improve treatment by monitoring drug interactions and patient compliance in those undergoing first-line therapy for metastatic hormone-positive breast cancer.

How Is the Trial Designed?

Group I: Health services research (DiviTum-TKa) Experimental Treatment 1 Intervention

Patients undergo collection of blood samples per SOC on days 1, 15, and 28 of cycle 1, days 15 and 28 of cycle 2, days 15 and 28 of cycle 3, and day 28 of subsequent cycles for up to 12 cycles for analysis by DiviTum-TKa in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Selective inhibitors targeting cyclin-dependent kinases (CDK) 4 and 6, such as palbociclib, ribociclib, and abemaciclib, have shown promising preclinical activity in treating luminal breast cancer and are currently under clinical evaluation.

Early studies indicate that these drugs can improve prognosis for metastatic breast cancer patients, especially when used in combination with endocrine therapy or as monotherapy, highlighting their potential role in personalized cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cell cycle inhibitors in endocrine receptor positive breast cancer]. Sablin, MP., Ricci, F., Loirat, D., et al.[2019]

Abemaciclib, a CDK4/6 inhibitor, significantly reduced levels of Ki67, a protein that indicates cell proliferation, in women with hormone receptor-positive, HER2-negative breast cancer.

The results from the phase II neoMONARCH trial suggest that using abemaciclib, either alone or with endocrine therapy, may be an effective neoadjuvant treatment for early-stage breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib Shows Promise for Early Breast Cancer. [2019]

Abemaciclib is a potent oral CDK4 and CDK6 inhibitor that effectively treats hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, showing response rates between 19.7% and 59% in major clinical trials.

The drug is well-tolerated, with common side effects including diarrhea and neutropenia, and it offers the advantage of continuous dosing and potential use as a monotherapy, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer. Palumbo, A., Lau, G., Saraceni, M.[2020]

The addition of CDK4 and 6 inhibitors (like abemaciclib, palbociclib, or ribociclib) to endocrine therapy significantly improves progression-free survival and response rates in patients with HR+ and HER2- metastatic breast cancer, establishing these inhibitors as a new standard of care.

Exploratory analyses suggest that abemaciclib may be particularly beneficial for women with poor prognosis indicators, although further confirmation is needed for these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib, a CDK4 and CDK6 inhibitor for the treatment of metastatic breast cancer. Martin, M., Garcia-Saenz, JA., Manso, L., et al.[2021]

A total of 1611 individual case safety reports were analyzed, revealing that palbociclib and ribociclib were associated with serious adverse drug reactions (ADRs) like leukopenia and thrombocytopenia, although most patients recovered from these conditions.

In contrast, abemaciclib was linked to mostly non-serious ADRs, indicating a potentially better safety profile, especially when combined with treatments like fulvestrant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematological Events Potentially Associated with CDK4/6 Inhibitors: An Analysis from the European Spontaneous Adverse Event Reporting System. Martins, V., Jesus, M., Pereira, L., et al.[2023]

Dinaciclib, a CDK 1/2/5/9 inhibitor, has shown promising results in preclinical studies and a good safety profile in Phase I trials, making it a potential treatment option for breast cancer and other malignancies.

The review emphasizes the need for a deeper understanding of how CDKs contribute to cancer and suggests that identifying biomarkers for dinaciclib's effectiveness could improve patient selection for clinical trials and enhance treatment strategies, including combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dinaciclib for the treatment of breast cancer. Criscitiello, C., Viale, G., Esposito, A., et al.[2021]

A new, highly sensitive method using liquid chromatography/electrospray ionization tandem mass spectrometry was developed to simultaneously measure levels of CDK4/6 inhibitors and aromatase inhibitors in patients with advanced breast cancer, ensuring effective therapeutic drug monitoring (TDM).

The method demonstrated excellent accuracy and precision, with low relative error and coefficient of variation values, making it suitable for clinical use to enhance the safety and efficacy of cancer treatments by monitoring drug concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment of an analytical method for simultaneous quantitation of CDK4/6 inhibitors, aromatase inhibitors, and an estrogen receptor antagonist in human plasma using LC-ESI-MS/MS. Sato, Y., Shigeta, K., Hirasawa, T., et al.[2021]

In a study of 396 female patients with hormone receptor positive, HER2-negative metastatic breast cancer receiving CDK4 and 6 inhibitors, the most common adverse events were neutropenia, diarrhea, and fatigue, with varying frequencies depending on the specific drug used.

The study found that while the overall incidence of adverse events was lower than in clinical trials, the rates of dose reductions and treatment holds due to these events were higher, suggesting that clinicians may be actively managing side effects to help patients continue their therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world incidence and management of adverse events in patients with HR+, HER2- metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting. Price, GL., Sudharshan, L., Ryan, P., et al.[2022]

CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib are effective treatments for hormone receptor-positive advanced breast cancer, with ribociclib and abemaciclib showing improved overall survival in clinical trials.

Abemaciclib is the only CDK4/6 inhibitor that has demonstrated sustained improvement in invasive disease-free survival in early breast cancer, highlighting differences in efficacy among these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors: existing and emerging differences. Johnston, S., Emde, A., Barrios, C., et al.[2023]

Thymidine kinase 1 (TK1) activity in blood is a dynamic biomarker that can indicate how well patients with advanced breast cancer respond to palbociclib, with significant changes observed after treatment.

In a study of 46 patients, a decrease in TK1 activity after one cycle of palbociclib correlated with better progression-free survival, while an increase in TK1 activity was linked to worse outcomes, suggesting it could help identify patients needing treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma Thymidine Kinase Activity as a Biomarker in Patients with Luminal Metastatic Breast Cancer Treated with Palbociclib within the TREnd Trial. McCartney, A., Bonechi, M., De Luca, F., et al.[2021]

In a phase II trial involving 124 post-menopausal women with hormone receptor-positive/HER2-negative metastatic breast cancer, serum thymidine kinase activity (sTKa) was identified as an independent prognostic biomarker for patients treated with palbociclib and fulvestrant.

The study found that higher levels of sTKa, especially if not adequately suppressed during treatment, were associated with shorter progression-free survival, indicating that monitoring sTKa could help identify patients at risk of poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum thymidine kinase activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with palbociclib and fulvestrant. Malorni, L., Tyekucheva, S., Hilbers, FS., et al.[2022]

CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, have significantly improved treatment outcomes for hormone receptor-positive and HER2-negative breast cancer, establishing themselves as key options in both first- and second-line therapies.

While these inhibitors effectively prolong overall survival and progression-free survival in patients, they are also associated with notable adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Overview of the Safety Profile and Clinical Impact of CDK4/6 Inhibitors in Breast Cancer-A Systematic Review of Randomized Phase II and III Clinical Trials. Stanciu, IM., Parosanu, AI., Nitipir, C.[2023]

Cyclin-dependent kinases 4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, have significantly improved treatment outcomes for hormone receptor-positive metastatic breast cancer, showing enhanced response rates and progression-free survival in Phase II-III clinical trials.

These inhibitors have manageable toxicity profiles and positively impact patients' quality of life, prompting ongoing research to identify differences among them for better clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are all cyclin-dependent kinases 4/6 inhibitors created equal? Marra, A., Curigliano, G.[2023]

Palbociclib has been approved for treating hormone receptor-positive advanced breast cancer due to its ability to improve progression-free survival when used with endocrine agents, highlighting its efficacy in this patient population.

Abemaciclib and ribociclib, two other CDK4/6 inhibitors, are in late-stage clinical development and may offer different benefits, such as single-agent activity and central nervous system penetration, which could influence treatment choices and patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer. Barroso-Sousa, R., Shapiro, GI., Tolaney, SM.[2020]

Citations

1. divitum.com divitum.com/

DiviTum® TKa: Innovative Biomarker Testing For Breast Cancer DiviTum TKa is a blood-based biomarker test that monitors and predicts treatment response in hormone receptor-positive metastatic breast cancer.

2. divitum.com divitum.com/knowledge-hub/clinical-evidence/

Clinical Evidence The DiviTum TKa test has been studied widely in HR+ metastatic breast cancer, as well as in other solid tumor types.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06388122

Study Details | NCT06388122 | DiviTum®TKa: A Biomarker ... The purpose of this study is to explore the clinical utility of routinely measuring thymidine kinase activity (TKa) in HR+ metastatic breast cancer patients ...

4. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/reviews/K202852.pdf

A 510(k) Number K202852 B Applicant Biov A TKa value of < 250 DuA is associated with the decreased likelihood of disease progression within 30 days or 60 days post testing. DiviTumTKa results should be ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.1028

Use of liquid biomarker thymidine kinase activity (TKa) to ... TKa is a liquid proliferation biomarker providing prognostic, predictive and monitoring information in MBC. TKa can be measured in blood using the DiviTum TKa ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10681159/

Thymidine kinase activity levels in serum can identify HR+ ... In that report, it was concluded that high serum TKa at baseline and at subsequent timepoints is associated with worse prognosis in patients starting first-line ...

7. divitum.com divitum.com/about-the-test/

Understand More About Our TKa Biomarker Test The DiviTum TKa test is an innovative tumor TK activity (TKa) profile test for early prognosis and prediction of mBC treatment outcomes in postmenopausal HR+ ...