DiviTum-TKa Assay for Breast Cancer

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

50 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug DiviTum-TKa Assay for Breast Cancer?

The CDK4/6 inhibitors, including palbociclib, ribociclib, and abemaciclib, have been shown to improve progression-free survival in patients with advanced or metastatic breast cancer when combined with hormone therapy. These drugs are now a standard treatment option for this type of cancer. ^{1 2 3 4 5}

Is the DiviTum-TKa Assay for Breast Cancer safe for humans?

CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib, which are related to the DiviTum-TKa Assay, have been shown to be generally safe in humans. They can cause side effects like low white blood cell counts (leukopenia) and low platelet counts (thrombocytopenia), but these are often manageable and patients usually recover. Overall, these treatments have a manageable safety profile and are well-tolerated in clinical settings. ^{6 7 8 9 10}

How does the DiviTum-TKa Assay differ from other breast cancer treatments?

The DiviTum-TKa Assay is unique because it measures thymidine kinase activity in the blood, which serves as a dynamic marker to predict outcomes in advanced breast cancer patients. This approach is different from standard treatments that focus on directly targeting cancer cells, as it provides a non-invasive way to monitor treatment response and adjust therapy accordingly. ^{3 11 12 13 14}

What is the purpose of this trial?

This clinical trial assesses whether using a test developed by DiviTum can identify optimal levels of CDK 4/6 inhibitor medications in the blood and whether assessing medical compliance and drug-drug interactions can optimize (improve) these levels in patients with estrogen receptor (ER) or progesterone receptor (PR) positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and are receiving CDK 4/6 inhibitors. CDK4/6 inhibitors in combination with endocrine therapy (ET) is first line treatment for metastatic hormone positive (ER/PR positive) breast cancer (mBC). Thymidine kinase is a biomarker (biological molecule found in blood, other body fluids, or tissues that is a sign of a condition or disease) that reflects cell proliferation (an increase in the number of cells as a result of cell growth and cell division). DiviTum-thymidine kinase activity (TKa) is a Food and Drug Administration approved assay which showed that a TKa is associated with the decreased likelihood of disease progression within 30 days or 60 days post testing. Using the DiviTum-TKa may improve medication compliance and remove potential drug-drug interactions in patients with ER/PR positive HER2-negative MBC.

Research Team

Mariya Rozenblit, MD

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors: existing and emerging differences. [2023]

2. France pubmed.ncbi.nlm.nih.gov

[Cell cycle inhibitors in endocrine receptor positive breast cancer]. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Dinaciclib for the treatment of breast cancer. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Abemaciclib, a CDK4 and CDK6 inhibitor for the treatment of metastatic breast cancer. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Hematological Events Potentially Associated with CDK4/6 Inhibitors: An Analysis from the European Spontaneous Adverse Event Reporting System. [2023]

7. Switzerland 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. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Are all cyclin-dependent kinases 4/6 inhibitors created equal? [2023]

10. England 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. [2022]

11. United States 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. [2021]

12. Netherlands 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. [2021]

13. England 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. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Abemaciclib Shows Promise for Early Breast Cancer. [2019]