Sequential Therapies for Breast Cancer

Overseen By Jennifer Childress

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressants

Disqualifiers: Brain metastasis, Active infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if using existing breast cancer drugs in a new sequence can improve treatment for metastatic breast cancer. Participants will receive a series of treatments involving drugs like Cytoxan and Taxotere, administered in stages. Women with hormone-positive, HER2-negative metastatic breast cancer, who have previously received specific hormone therapies, might be suitable candidates. The study seeks individuals with measurable disease and elevated tumor markers visible on imaging scans. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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, you cannot participate if you have used any investigational drugs within 30 days before the study or if you are on certain immunosuppressive medications. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown varying levels of safety and patient tolerance for the drugs used in this clinical trial.

Research on the Cytoxan and Taxotere combination in early breast cancer patients found no major safety issues, indicating good tolerance. Sacituzumab govitecan, approved for another type of breast cancer, has been well-tolerated in studies. Common side effects include low blood cell counts, nausea, and tiredness, but these are usually manageable. Trastuzumab deruxtecan has a safety profile where some patients experienced lung-related side effects, though these are uncommon. Capecitabine, often used in breast cancer treatments, demonstrated significant tumor control in patients with extensive prior treatments, with generally manageable side effects. Finally, the combination of Fulvestrant and CDK 4/6 inhibitors (such as ribociclib or abemaciclib) is considered safe for patients with certain types of breast cancer, with studies showing survival benefits.

Overall, while some side effects exist, research findings suggest these treatments are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these sequential therapies for breast cancer because they offer a novel combination approach that targets the disease from multiple angles. Unlike the standard of care, which often involves single-agent therapies like hormone blockers or chemotherapy, this sequence combines chemotherapy (Cytoxan, Taxotere), antibody-drug conjugates (sacituzumab govitecan, trastuzumab deruxtecan), and CDK 4/6 inhibitors (ribociclib, abemaciclib) to attack cancer cells in different ways. This multi-pronged strategy aims to enhance effectiveness and potentially overcome resistance mechanisms seen with traditional treatments. Additionally, the inclusion of capecitabine introduces an oral chemotherapy option for convenience and flexibility in treatment plans. Researchers hope these therapies will lead to better outcomes by exploiting the unique strengths of each drug in the sequence.

What evidence suggests that this trial's treatments could be effective for metastatic breast cancer?

This trial will administer sequential therapies for breast cancer. Studies have shown that combining Cytoxan and Taxotere, which participants in this trial may receive, effectively treats breast cancer, with many patients responding well. Sacituzumab govitecan, another treatment option in this trial, has helped patients with triple-negative breast cancer live longer without disease progression compared to standard chemotherapy. Trastuzumab deruxtecan, also part of this trial, has successfully lowered the chances of recurrence or death in patients with both HER2-positive and HER2-low metastatic breast cancer. Capecitabine, included in the trial, has effectively controlled tumors in patients who have already undergone many treatments. The combination of Fulvestrant with CDK 4/6 inhibitors, such as ribociclib and abemaciclib, is another treatment sequence in this trial and has significantly improved progression-free survival and overall survival in hormone-receptor-positive breast cancer. These treatments show promising results in managing different types of breast cancer. ^{1 3 4 5 6}

Who Is on the Research Team?

Aixa Soyano, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic breast cancer. Participants should be suitable to receive the study drugs, which are all approved treatments. Specific eligibility criteria were not provided, so interested individuals should contact the study team for more details.

Inclusion Criteria

I am not pregnant.

I can understand and am willing to sign the consent form myself or have someone legally authorized to do so on my behalf.

I am fully active or can carry out light work.

Exclusion Criteria

I haven't taken any experimental drugs in the last 30 days.

I haven't been treated for another cancer within the last 2 years.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Strike 1

Participants receive Cytoxan/Taxotere/GM-CSF as the first strike in the sequential therapy

4-6 weeks

Treatment - Strike 2

Participants receive Sacituzumab govitecan or trastuzumab deruxtecan as the second strike in the sequential therapy

4-6 weeks

Treatment - Strike 3

Participants receive Capecitabine as the third strike in the sequential therapy

4-6 weeks

Treatment - Strike 4

Participants receive Fulvestrant + CDK 4/6 inhibitor (ribociclib or abemaciclib) as the fourth strike in the sequential therapy

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Cytoxan
• Fulvestrant
• Ribociclib
• Sacituzumab govitecan
• Taxotere
• Trastuzumab deruxtecan
• Xeloda

Trial Overview The trial is testing a new treatment strategy using existing drugs: Abemaciclib, Sacituzumab govitecan, Trastuzumab deruxtecan, Xeloda (capecitabine), Taxotere (docetaxel), Cytoxan (cyclophosphamide), Fulvestrant and Ribociclib. The goal is to see if administering these drugs sequentially based on evolutionary dynamics can improve outcomes in metastatic breast cancer.

How Is the Trial Designed?

Group I: Sequential therapy Experimental Treatment 8 Interventions

In this study sequential therapies will be administered. Strike 1: Cytoxan/Taxotere/GM-CSF Strike 2: Sacituzumab govitecan or trastuzumab deruxtecan Strike 3: Capecitabine Strike 4: Fulvestrant + CDK 4/6 inhibitor (ribociclib or abemaciclib)

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Published Research Related to This Trial

Cytotoxic chemotherapy remains a key treatment for metastatic breast cancer (MBC), with options like re-challenge with anthracyclines or taxanes, capecitabine, and newer agents like etirinotecan pegol showing promising results in phase II studies.

Etirinotecan pegol, a novel cytotoxic agent, is being further evaluated in the phase III BEACON trial, highlighting the ongoing search for effective treatments that target new pathways and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxic chemotherapy: Still the mainstay of clinical practice for all subtypes metastatic breast cancer. Twelves, C., Jove, M., Gombos, A., et al.[2022]

The combination of trastuzumab, capecitabine, and docetaxel showed a significant overall survival benefit in HER-2-positive breast cancer patients, with a median overall survival of 25.5 months and a median progression-free survival of 7.8 months, based on a study of 29 patients.

The treatment regimen was well tolerated, with a low incidence of severe side effects, and no cardiac toxicity reported, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab plus capecitabine and docetaxel as first-line therapy for HER2-positive metastatic breast cancer: phase II results. Michalaki, V., Fotiou, S., Gennatas, S., et al.[2018]

Standard treatments for breast cancer after initial chemotherapy include capecitabine, S-1, vinorelbine, irinotecan, or gemcitabine, which are effective options for managing the disease.

Newer therapies like lapatinib for trastuzumab-resistant cases and combinations like bevacizumab with taxanes show promise, highlighting the need for further research on optimal drug sequences and combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for breast cancer refractory to anthracycline, taxane or trastuzumab]. Ito, Y., Kobayashi, K.[2016]

In a study of 658 women with high-risk node-negative early breast cancer, the sequential chemotherapy regimen (epirubicin followed by docetaxel) showed a non-significant but potentially meaningful improvement in disease-free survival (DFS) rates at 5 years (92.6% vs 88.2% for concurrent therapy).

The sequential regimen was associated with higher rates of grade 2-4 neutropenia and nausea/vomiting compared to the concurrent regimen, but there were no toxic deaths, indicating that while the sequential approach may improve outcomes, it also carries a higher risk of certain side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group. Mavroudis, D., Saloustros, E., Boukovinas, I., et al.[2018]

Trastuzumab (Herceptin) combined with endocrine therapy is a promising treatment for women with less aggressive, estrogen receptor/HER2-positive metastatic breast cancer, while for aggressive HER2-positive cases, it significantly improves survival when used with chemotherapy, particularly taxanes.

Trastuzumab has a favorable safety profile, adding little toxicity to taxane chemotherapy, and enhances quality of life compared to chemotherapy alone, making it a viable option for patients who may not tolerate cytotoxic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maximizing clinical benefit with trastuzumab. Bell, R., Verma, S., Untch, M., et al.[2019]

In a study of 40 patients with HER-2-positive advanced breast cancer who had previously failed other treatments, the combination of capecitabine and trastuzumab showed a median time to progression of 8 months and an overall survival of 24 months, indicating its efficacy in this heavily pretreated population.

The treatment was generally well-tolerated, with only mild to moderate adverse effects reported, such as diarrhea (5%) and hand-foot syndrome (15%), suggesting that capecitabine plus trastuzumab is a safe option for patients in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer. Bartsch, R., Wenzel, C., Altorjai, G., et al.[2022]

Taxanes, particularly paclitaxel and docetaxel, have been shown to significantly impact the treatment of early-stage breast cancer, with large-scale phase III trials confirming their potential to change the disease's natural history.

The strategies for using these drugs differ, with paclitaxel primarily used in sequential regimens and docetaxel in both sequential and combination therapies, highlighting the need for further research to determine the optimal use of taxanes for maximum patient benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the use of taxanes in the adjuvant therapy of breast cancer. Nabholtz, JM., Vannetzel, JM., Llory, JF., et al.[2019]

Capecitabine is a well-tolerated treatment for metastatic breast cancer, showing minimal side effects like myelosuppression and hair loss, which makes it a promising option for combination therapies with other anticancer drugs.

Ongoing phase II/III trials are investigating the use of capecitabine in early breast cancer treatment, and preliminary results indicate that it may provide significant benefits when used as part of adjuvant and neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer. Fumoleau, P., Cameron, D.[2019]

Fam-trastuzumab deruxtecan-nxki (ENHERTU) received accelerated FDA approval for treating HER2-positive breast cancer in patients who have already undergone two or more anti-HER2 therapies, based on a study involving 184 patients that showed a confirmed overall response rate of 60.3%.

While ENHERTU is effective, it carries significant risks, including severe interstitial lung disease and neutropenia, highlighting the importance of monitoring for serious side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer. Narayan, P., Osgood, CL., Singh, H., et al.[2022]

Capecitabine, when combined with docetaxel, has shown superior effectiveness compared to doxorubicin and cyclophosphamide in neoadjuvant treatment for early breast cancer, with a manageable safety profile.

A large ongoing trial program involving over 20,000 patients is investigating various capecitabine treatment strategies in early breast cancer, indicating its potential for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine: expanding options for the treatment of patients with early or locally advanced breast cancer. Wardley, A.[2015]

Sequential chemotherapy using doxorubicin followed by cyclophosphamide/methotrexate/5-fluorouracil (CMF) has been shown to be superior for patients with high-risk resectable breast cancer, improving disease-free and overall survival.

Early results from phase II trials indicate that adding paclitaxel to the sequential regimen of doxorubicin and cyclophosphamide is feasible and shows promising disease-free survival outcomes, suggesting potential for enhanced effectiveness in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential adjuvant therapy: the Memorial Sloan-Kettering Cancer Center experience. Hudis, C., Seidman, A., Raptis, G., et al.[2015]

Citations

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Capecitabine efficacy after cycline-dependent-kinase 4/6 ... Capivasertib, an AKT inhibitor, showed favourable results in endocrine resistant breast cancer with a 7.3-month PFS. In this phase III study, 69% of the ...

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