This phase II trial tests how well a sequential treatment plan works in treating breast cancer that is hormone positive and has spread from where it first started (primary site) to other places in the body (metastatic). The usual way that most anticancer drugs are given is to give a treatment for as long as it takes for that drug(s) to either cure the cancer, prove to no longer be working, or cause unacceptable side effects. If the first treatment used against the cancer fails, another treatment is started with a different approved drug. With a sequential treatment plan, waiting until the cancer has completely gone away or worsened before changing drugs does not happen. Instead, treatment changes to a second, third, and fourth treatment when it is predicted the effectiveness of each drug has reached its peak. It is hoped that by not giving the cancer a chance to adapt to the drug or begin to grow again, that the next set of treatment will have a better chance at killing the cancer. The sequential treatment plan in this trial uses drugs that may already be used in the treatment of hormone positive metastatic breast cancer. Docetaxel is in a class of medications called taxanes. It stops cancer cells from growing and dividing and may kill them. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell’s DNA and may kill tumor cells. It may also lower the body’s immune response. Capecitabine is in a class of medications called anti-metabolites. It is taken up by tumor cells and breaks down into fluorouracil, a substance that kills tumor cells. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Sacituzumab govitecan is also an antibody-drug conjugate. It is composed of a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug, called govitecan. Sacituzumab attaches to a receptor called TROP2 on tumor cells and delivers govitecan to kill them. Fulvestrant is a type of antiestrogen, it works by blocking estrogen activity in the body which may help stop the growth of tumor cells. Ribociclib and abemaciclib are cyclin-dependent kinase inhibitors, they stop an enzyme that catalyzes the addition of a phosphate group to a protein in the cell cycle regulation pathway. Stopping the enzyme results in cell death. Following a sequential treatment plan may be more effective at treating hormone positive metastatic breast cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06409390.
Locations matching your search criteria
United States
Florida
Tampa
Moffitt Cancer CenterStatus: Active
Contact: Aixa Elena Soyano
Phone: 813-745-4673
PRIMARY OBJECTIVE:
I. To examine the feasibility of sequential therapy (ST) modeled on evolutionary dynamics in the treatment of metastatic breast cancer (MBC).
SECONDARY OBJECTIVES:
I. To explore preliminary efficacy of sequential therapy (ST) modeled on evolutionary dynamics in the treatment of MBC.
II. To evaluate and assess safety of sequential (“first strike, second strike”) therapies.
III. To assess biomarkers in prediction of response.
IV. To build and refine a mathematical model of the “first strike, second strike” strategy based on clinical and biomarker data.
TERTIARY/EXPLORATORY OBJECTIVES:
I. To evaluate the effect of “first strike, second strike” sequential therapies (ST) modeled on evolutionary dynamics on overall 5-year survival rate.
II. Evaluate changes in imaging biomarkers occurring in patients treated with sequential therapy (ST) modeled on evolutionary dynamics.
III. Evaluate the effect of “first strike, second strike” sequential therapies (ST) modeled on evolutionary dynamics on MBC tumor markers.
IV. To measure the effects of quality of life using “first strike, second strike” sequential therapies.
OUTLINE:
1ST STRIKE: Patients receive docetaxel and cyclophosphamide intravenously (IV) over 1 hour on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
2ND STRIKE: Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 of each cycle or sacituzumab govitecan IV over 1-3 hours on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.
3RD STRIKE: Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14 of each cycle. Cycles repeat every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.
4TH STRIKE: Patients receive fulvestrant intramuscularly (IM) over 1-2 minutes on days 1, 15, and 28 of cycle 1 and then on day 1 of cycles 2-4. Patients also receive ribociclib PO once daily (QD) days 1-21 of each cycle or abemaciclib PO BID days 1-28 of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI), bone scan, and/or positron emission tomography (PET) during screening and throughout the trial.
After completion of study treatment patients are followed up at 30 days and then every 6 months for up to 5 years.
Lead OrganizationMoffitt Cancer Center
Principal InvestigatorAixa Elena Soyano
