Epidiferphane + Taxane Chemotherapy for Breast Cancer

Overseen By Priya Gurjar

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Florida

Must be taking: Taxane chemotherapy

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: Pregnancy, Infection, Psychiatric illness, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding a supplement called Epidiferphane to taxane chemotherapy (including drugs like Paclitaxel, Docetaxel, and Nab-paclitaxel) can reduce common side effects such as anemia and nerve damage in breast cancer treatment. Researchers aim to determine if this combination can also enhance the cancer's response to treatment. It suits those beginning taxane chemotherapy for breast cancer at UF Health and who agree to avoid green tea and curcumin supplements during the trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on strong CYP3A4 inhibitors like tacrolimus or verapamil during the trial.

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

Research shows that Epidiferphane, when combined with taxane chemotherapy, is under careful study for its safety in treating breast cancer. Previous studies suggest that Epidiferphane might reduce common side effects of taxane drugs, such as anemia (low red blood cell count) and peripheral neuropathy (nerve damage causing pain or numbness). These side effects often necessitate changes in treatment plans, impacting overall treatment success.

Although taxane chemotherapy is generally considered safe, side effects can still occur. Researchers are testing the combination with Epidiferphane to determine if it can reduce these side effects. As this trial is in the early stages, researchers are still determining the safest and most effective dose. In earlier studies, participants began with lower doses of taxane and gradually increased to the full dose to monitor for any negative effects.

Overall, evidence suggests that the combination is being thoroughly studied and monitored for safety, but the complete safety profile is still being established. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Epidiferphane combined with taxane chemotherapy is unique because it introduces a novel active ingredient, Epidiferphane, which is being explored to enhance the effectiveness of existing treatments. While standard breast cancer treatments often involve taxane-based chemotherapy, the addition of Epidiferphane might offer a new mechanism of action that could potentially improve outcomes. Researchers are excited about this combination because it could provide a more targeted approach, potentially leading to better efficacy and fewer side effects compared to traditional chemotherapy alone.

What evidence suggests that Epidiferphane might be an effective treatment for reducing side effects in breast cancer patients receiving taxane chemotherapy?

Research has shown that adding Epidiferphane to taxane chemotherapy, which participants in this trial will receive, might reduce common side effects like anemia (low red blood cell count) and neuropathy (nerve damage). Studies in mice found that Epidiferphane lessened these side effects when used with chemotherapy drugs like paclitaxel. This could enable patients to continue their treatment plans more easily, potentially leading to better outcomes. Early findings also suggest that this combination could slow tumor growth. While research in humans continues, these initial results are promising for improving the treatment experience for breast cancer patients. ^{1 4 5 6 7}

Who Is on the Research Team?

Coy Heldermon, M.D., PhD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

Adults with breast cancer starting a new taxane chemotherapy regimen at UF Health may join this trial. They must have good performance status, no more than one active cancer, and a functioning digestive tract without obstruction. Participants should not be pregnant or breastfeeding, avoid green tea and curcumin supplements, and use effective contraception.

Inclusion Criteria

My digestive system is working well without blockages.

Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study.

I am using effective birth control to prevent pregnancy during the study.

Exclusion Criteria

Must not be receiving any other investigational agents

My bilirubin levels are higher than normal, possibly due to Gilbert's Syndrome.

Your ALT or AST levels are more than 2.5 times the normal limit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive taxane chemotherapy and Epidiferphane to assess the attenuation of side effects and improvement in tumor response rate

3 months

Regular visits for chemotherapy administration and monitoring

Pharmacokinetics Assessment

Blood concentration measurements of taxanes and Epidiferphane components at various time points

24 hours

Multiple visits for blood sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Epidiferphane
• Taxane Chemotherapy

Trial Overview The study is testing whether Epidiferphane can reduce side effects like anemia and neuropathy in patients receiving taxane chemotherapy for breast cancer. It will also determine the safety of Epidiferphane and its maximum tolerated dose alongside standard treatment.

How Is the Trial Designed?

Group I: Epidiferphane + taxane chemotherapy Experimental Treatment 2 Interventions

Taxane Chemotherapy is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxanes for:

• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer
• Prostate cancer
• Stomach cancer

Approved in European Union as Taxanes for:

• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer
• Prostate cancer
• Stomach cancer

Approved in Canada as Taxanes for:

• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer
• Prostate cancer
• Stomach cancer

Approved in Japan as Taxanes for:

• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer
• Prostate cancer
• Stomach cancer

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

In the DEVA trial involving 803 postmenopausal women with node-positive early breast cancer, the combination of epirubicin followed by docetaxel (EPI-DOC) significantly improved disease-free survival (DFS) rates to 79.5% compared to 72.7% for epirubicin alone, indicating a more effective treatment regimen.

While the EPI-DOC regimen showed better overall survival rates (88.9% vs. 81.8% for epirubicin alone), it was associated with greater toxicity; however, there was no difference in quality of life between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, phase III trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with node-positive breast cancer. Coombes, RC., Bliss, JM., Espie, M., et al.[2018]

Taxanes, such as docetaxel and paclitaxel, are widely used anticancer drugs for various cancers, but they are associated with significant dermatological adverse events (AEs) that have not been thoroughly studied in a prospective manner.

Understanding and managing these skin, hair, and nail toxicities is crucial for maintaining the quality of life in cancer patients and preventing necessary dose adjustments in their treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatological adverse events with taxane chemotherapy. Sibaud, V., Lebœuf, NR., Roche, H., et al.[2022]

Docetaxel is an effective treatment for metastatic breast cancer, particularly in patients whose cancer has progressed after anthracycline therapy, and it works by blocking tumor cell division during the M phase of the cell cycle.

The drug has a recommended dosage of 60-100 mg/m2 administered intravenously every three weeks, but it can cause significant side effects like neutropenia, mucositis, and hypersensitivity reactions, and is not suitable for patients with liver metastases or impaired liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: a taxoid for the treatment of metastatic breast cancer. Tankanow, RM.[2019]

Adjuvant chemotherapy, particularly with taxanes like docetaxel, significantly reduces the risk of relapse and cancer-related mortality in early-stage breast cancer, highlighting its efficacy in treatment.

Clinical trials have demonstrated that combining taxanes with targeted therapies enhances their effectiveness in managing breast cancer, supporting the continued use of docetaxel in patients with node-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel for the post-surgery treatment of patients with node-positive breast cancer. Pant, S., Chilukuri, MP., Ramaswamy, B.[2022]

Docetaxel is highly effective in treating breast cancer, achieving response rates of 41% as a second-line treatment and 50-72% as a first-line therapy, with meaningful response durations of 7-8 months.

The main side effect of docetaxel is short-duration, non-cumulative neutropenia, and no cumulative cardiotoxicity has been observed, making it a promising candidate for combination therapies in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospects with docetaxel in the treatment of patients with breast cancer. Marty, M., Extra, JM., Cottu, PH., et al.[2019]

In a study involving 42 patients with advanced breast cancer, the combination of epidoxorubicin and docetaxel was found to be effective and safe, achieving an overall response rate of 60%, particularly in patients with liver disease (58%) and soft tissue involvement (84%).

The maximum tolerated dose (MTD) was established at 120 mg/m2 of epidoxorubicin and 85 mg/m2 of docetaxel with granulocyte colony-stimulating factor (G-CSF) support, allowing for higher doses without severe toxicity, although increasing the dose did not improve response rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-finding study of epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer. Pagani, O., Sessa, C., Martinelli, G., et al.[2020]

The TEC regimen, which includes docetaxel, epirubicin, and cyclophosphamide, demonstrated a pathologic complete response rate of 25% in a phase II study involving 20 patients with locally advanced breast cancer.

The treatment was well-tolerated, with a 5-year overall survival rate of 94.7% and no cases of cardiac failure or treatment-related deaths, although neutropenia was a common side effect in 35% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Concurrent Docetaxel, Epirubicin and Cyclophosphamide as a Neoadjuvant Chemotherapy Regimen in Patients with Locally Advanced Breast Cancer. Yao, X., Hosenpud, J., Chitambar, CR., et al.[2021]

In a study of 43 women with metastatic breast cancer treated with nab-paclitaxel, 76.2% of those receiving weekly treatment experienced clinical benefits, indicating that this chemotherapy is effective for many patients.

The treatment was generally well tolerated, with mild sensory neuropathy being the main side effect, and those who experienced clinical benefits had a significantly longer median overall survival of 17.3 months compared to 7.7 months for those who did not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of women with metastatic breast cancer treated with nab-paclitaxel: experience from a single academic cancer centre. Dent, S., Fraser, J., Graham, N., et al.[2022]

In a phase II study involving 200 Japanese patients with metastatic breast cancer, weekly nab-paclitaxel showed similar efficacy to docetaxel, with median progression-free survival of 9.8 months for nab-paclitaxel compared to 11.2 months for docetaxel, indicating that both treatments are effective options.

Nab-paclitaxel had a lower incidence of severe neutropenia (35.0%) compared to docetaxel (89.0%), suggesting a potentially safer profile regarding this common side effect, although both treatments had similar overall adverse event rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of nab-paclitaxel as first-line chemotherapy in patients with HER2-negative metastatic breast cancer. Tamura, K., Inoue, K., Masuda, N., et al.[2022]

In a review of five phase III clinical trials, docetaxel was associated with a higher incidence of grade 3/4 neutropenia compared to paclitaxel, indicating a distinct safety profile for each taxane.

Paclitaxel was more likely to cause peripheral neuropathy, while docetaxel had higher rates of gastrointestinal adverse events, suggesting that the choice of taxane may depend on the patient's tolerance to these specific side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systemic review of taxanes and their side effects in metastatic breast cancer. Lai, JI., Chao, TC., Liu, CY., et al.[2022]

Docetaxel (Taxotère) has shown significant efficacy in breast cancer treatment, particularly in adjuvant settings, where it improved disease-free survival compared to the FAC regimen, especially in patients with fewer than four positive lymph nodes.

In neoadjuvant settings, adding docetaxel after anthracycline treatment led to better clinical responses and increased pathological response rates, indicating its potential to enhance breast conservation and overall treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Update on docetaxel and breast cancer]. Diéras, V., Girre, V., Pierga, JY., et al.[2018]

Taxanes, while effective in treating breast cancer, pose greater toxicity risks in older patients, necessitating careful treatment planning to balance efficacy and safety, especially since elderly women are increasingly affected by breast cancer.

In metastatic breast cancer, weekly paclitaxel and three-weekly docetaxel are commonly used with acceptable toxicity, but the standard three-weekly docetaxel dose of 100mg/m² is not suitable for elderly patients, highlighting the need for tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxanes in the treatment of breast cancer: Have we better defined their role in older patients? A position paper from a SIOG Task Force. Biganzoli, L., Aapro, M., Loibl, S., et al.[2022]

Paclitaxel and docetaxel are effective treatments for breast cancer, with paclitaxel showing a response rate of 20% to 60% in various patient groups, and docetaxel achieving approximately 70% major responses in untreated patients.

Both drugs have significant side effects: paclitaxel can cause neutropenia and peripheral neuropathy, while docetaxel is associated with fluid retention syndrome and may limit its use in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of taxanes in the treatment of breast cancer. Capri, G., Tarenzi, E., Fulfaro, F., et al.[2018]

Citations

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Epidiferphane and Taxane Chemotherapy for the ... This phase I/II trial tests the safety, side effects, best dose, and effectiveness of epidiferphane in combination with taxane chemotherapy in treating ...

2. withpower.com withpower.com/trial/epidiferphane-taxane-chemotherapy-for-breast-cancer-c3818

Epidiferphane + Taxane Chemotherapy for Breast Cancer This study will investigate whether the use of Epidiferphane in patients with breast cancer receiving taxane chemotherapy results in an attenuation of the side ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22728026/

Phase II trial of nab-paclitaxel compared with docetaxel as ... A randomized phase II study in first-line MBC demonstrated superior efficacy and safety of weekly nab-paclitaxel compared with docetaxel.

4. cancertherapyadvisor.com cancertherapyadvisor.com/home/cancer-topics/breast-cancer/breast-cancer-epidiferphane-taxanes/

Clinical Trial: Epidiferphane and Taxanes in Breast Cancer The study's primary outcomes include various pharmacokinetic measures, the maximum tolerated dose of epidiferphane, and rates of neuropathy and ...

5. youtube.com youtube.com/watch?v=8w7GbB76mfo

Investigating epidiferphane with taxane chemotherapy in ... We decided to test this this combination in our multiple xenograph models and we showed that it delayed growth of the tumors.

6. clinicaltrial.be clinicaltrial.be/en/details/174247?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Pharmacokinetics and Safety of Epidiferphane ... This study will investigate whether the use of Epidiferphane in patients with breast cancer receiving taxane chemotherapy results in an ...

7. onclive.com onclive.com/view/dr-heldermon-on-a-phase-1-2-trial-design-of-epidiferphane-plus-a-taxane-in-breast-cancer

Dr Heldermon on a Phase 1/2 Trial Design ... In the study, patients with breast cancer started at half of the target taxane dose before receiving the full target dose, Heldermon begins.