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

74 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with breast cancer are commonly treated with taxane chemotherapy. Some very common side effects of taxanes, such as anemia and peripheral neuropathy, are often as not well addressed during treatment, resulting in dose reductions, dose delays and early discontinuation (collectively called relative dose intensity) of these chemotherapy agents in 15-80 % of patients on these drugs. This reduction in relative dose intensity (RDI) results in worse clinical outcomes such as progression free and overall survival. Pre-clinical studies in mouse models subjected to standardized chemotherapy regimens containing paclitaxel or oxaliplatin have shown that the nutritional supplement Epidiferphane reduces both neuropathy and anemia. This study will investigate whether the use of Epidiferphane in patients with breast cancer receiving taxane chemotherapy results in an attenuation of the side effects experienced, as well as an improvement in tumor response rate. The safety and maximum tolerated dose of Epidiferphane in this patient population will also be determined in this study.

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.

What data supports the effectiveness of the drug Epidiferphane + Taxane Chemotherapy for breast cancer?

Research shows that docetaxel, a component of the treatment, is highly effective in treating breast cancer, especially in combination with other drugs. It has shown significant benefits in both early and advanced stages of breast cancer, improving survival rates and response to treatment. ^{1 2 3 4 5}

What safety information is available for Epidiferphane and Taxane Chemotherapy in humans?

Taxane chemotherapy, including drugs like paclitaxel, docetaxel, and nab-paclitaxel, is generally safe but can cause side effects. Common side effects include neutropenia (low white blood cell count), peripheral neuropathy (nerve damage causing tingling or numbness), and skin, hair, and nail issues. These side effects are usually manageable with proper care. ^{6 7 8 9 10}

What makes the drug Epidiferphane + Taxane Chemotherapy unique for breast cancer treatment?

Epidiferphane + Taxane Chemotherapy is unique because it combines taxanes like docetaxel, which are highly effective in breast cancer, with other agents to potentially enhance treatment efficacy. This combination is being explored to optimize dosing and reduce side effects, such as neutropenia (low white blood cell count), which is a common issue with taxane treatments. ^{4 5 11 12 13}

Research Team

Coy Heldermon, M.D., PhD

Principal Investigator

University of Florida

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. France pubmed.ncbi.nlm.nih.gov

[Update on docetaxel and breast cancer]. [2018]

2. England pubmed.ncbi.nlm.nih.gov

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

3. New Zealand pubmed.ncbi.nlm.nih.gov

Docetaxel for the post-surgery treatment of patients with node-positive breast cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Prospects with docetaxel in the treatment of patients with breast cancer. [2019]

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

Dose-finding study of epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer. [2020]

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

Clinical outcomes of women with metastatic breast cancer treated with nab-paclitaxel: experience from a single academic cancer centre. [2022]

7. Netherlands 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Randomized phase II study of nab-paclitaxel as first-line chemotherapy in patients with HER2-negative metastatic breast cancer. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

A systemic review of taxanes and their side effects in metastatic breast cancer. [2022]

10. France pubmed.ncbi.nlm.nih.gov

Dermatological adverse events with taxane chemotherapy. [2022]

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

The role of taxanes in the treatment of breast cancer. [2018]

12. Australia 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. [2021]

13. United States 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. [2018]