Eribulin + AC Chemotherapy for Breast Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Antiretrovirals, Eribulin, Paclitaxel, others

Disqualifiers: Pregnancy, HIV, Cardiac illness, 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

Compensation: Varies

Number of Visits: 11

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug eribulin can improve treatment for individuals with HER2-negative inflammatory breast cancer, an aggressive form of breast cancer. It combines eribulin with standard chemotherapy drugs, adriamycin and cyclophosphamide (also known as Cytoxan, Neosar, or Endoxan), to determine if this combination is more effective before surgery. Two groups participate: one receives eribulin first, while the other begins with standard chemotherapy. Those with confirmed inflammatory breast cancer without HER2 positivity and no evidence of cancer spread to organs or bones may be suitable candidates. Participants will also undergo surgery and possibly radiation or hormone therapy, depending on their condition. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on investigational agents or HIV antiretroviral therapy, you would not be eligible to participate.

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

Research has shown that eribulin, when combined with Adriamycin (also known as doxorubicin) and Cyclophosphamide, is generally well-tolerated in breast cancer treatments. Studies have found that eribulin can significantly improve survival rates in breast cancer patients, even those who have undergone several prior treatments.

Other studies indicate that patients using this combination experience manageable side effects. Common side effects include tiredness, low white blood cell counts, and hair loss. These effects are typical with many chemotherapy treatments and usually don't last long.

Overall, the combination of eribulin with Adriamycin and Cyclophosphamide has been studied in various settings, demonstrating a safety profile similar to other cancer treatments. Patients considering joining a trial should discuss potential side effects and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Eribulin with Adriamycin and Cyclophosphamide for breast cancer because it offers a unique approach compared to standard chemotherapy options. Eribulin, derived from a natural marine sponge, works differently by inhibiting microtubule dynamics, which can potentially prevent cancer cells from dividing and spreading. Unlike traditional treatments that mainly focus on DNA damage, Eribulin provides a novel mechanism that may enhance the effectiveness of existing drugs when used in combination. This fresh angle on treatment has the potential to improve outcomes and offer hope for better management of breast cancer.

What evidence suggests that this trial's treatments could be effective for HER2 negative inflammatory breast cancer?

Research has shown that eribulin, which participants in this trial may receive, offers promising results in extending the lives of patients with metastatic breast cancer. One study found that eribulin improved survival rates compared to other treatments selected by doctors. In this trial, participants will receive either eribulin followed by Adriamycin (doxorubicin) and Cyclophosphamide (Arm A) or Adriamycin and Cyclophosphamide followed by eribulin (Arm B). The combination of Adriamycin and Cyclophosphamide damages the DNA of cancer cells, preventing their growth. This combination is a well-known treatment for breast cancer and has been shown to extend patient survival, regardless of hormone receptor status. Together, these treatments offer hope by potentially enhancing the effectiveness of preoperative therapy for HER2 negative inflammatory breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Filipa Lynce, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HER2-negative inflammatory breast cancer, no prior therapy for one affected breast, and no metastatic cancer in organs or bones. Participants need normal heart function and organ/marrow health, must not be pregnant or breastfeeding, agree to use contraception, and have no severe illnesses that could affect study participation.

Inclusion Criteria

I am mostly able to carry out my daily activities.

My blood tests show my organs are functioning well.

I have been diagnosed with inflammatory breast cancer.

Exclusion Criteria

Your heart's electrical activity (QT interval) is longer than normal.

You have had allergic reactions to drugs similar to eribulin or other drugs being used in the study.

I am HIV-positive and on combination antiretroviral therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Therapy

Participants receive preoperative chemotherapy with either Eribulin followed by AC or AC followed by Eribulin

20 weeks

8 cycles of treatment

Surgery

Surgical removal of the breasts (Mastectomy) and axillary lymph node dissection

Radiation Therapy

Participants receive radiation therapy post-surgery

Follow-up

Participants are monitored for disease-free survival and overall survival

5 years

Every 3 months for 1 year, then every 6 months for 4 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Adriamycin
• Cyclophosphamide
• Eribulin

Trial Overview The study tests eribulin combined with standard chemotherapy drugs Adriamycin (doxorubicin) and Cyclophosphamide as a preoperative treatment. It aims to evaluate the effectiveness of this drug combination in treating patients before they undergo surgery for their breast cancer.

How Is the Trial Designed?

Group I: Arm B: AC > Eribulin Experimental Treatment 3 Interventions

* Adriamycin (doxorubicin) via iv a predetermined dosage and schedule per cycle * Cyclophosphamide (AC) via iv a predetermined dosage and schedule per cycle * Two research breast biopsies * Eribulin-Administered via iv, at predetermined dosage and schedule per cycle * Surgical Removal of the breasts (Mastectomy) and axillary lymph node dissection * Radiation Therapy * Endocrine Therapy (if applicable) * Optional 5 Patient-Optional DCE-MRI (Dynamic Contrast Enhanced-Magnetic Resonance Imaging) scans

Group II: Arm A: Eribulin > AC Experimental Treatment 3 Interventions

* Eribulin-Administered via iv, at predetermined dosage and schedule per cycle * Two research breast biopsies * Adriamycin (doxorubicin) via iv a predetermined dosage and schedule per cycle * Cyclophosphamide (AC) via iv a predetermined dosage and schedule per cycle * Surgical Removal of the breasts (Mastectomy) and axillary lymph node dissection * Radiation Therapy * Endocrine Therapy (if applicable) * Optional 5 Patient-Optional DCE-MRI (Dynamic Contrast Enhanced-Magnetic Resonance Imaging) scans

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Eisai Inc.

Industry Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Published Research Related to This Trial

In a phase II clinical trial involving 55 patients with operable breast cancer, preoperative chemotherapy using nanoparticle albumin-bound paclitaxel (nab-PTX) followed by an epirubicin and cyclophosphamide regimen achieved a pathological complete response (pCR) rate of 22.2%, indicating its efficacy in treating this condition.

The study found that HER2-positive patients had a significantly higher pCR rate of 60%, suggesting that HER2 status is an important factor in predicting treatment response, while the overall safety profile of the treatment was considered tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer: a multicenter phase II trial. Futamura, M., Nagao, Y., Ishihara, K., et al.[2018]

Eribulin mesylate is an FDA-approved treatment for patients with metastatic breast cancer who have already undergone at least two chemotherapy regimens, including an anthracycline and a taxane.

This drug is specifically designed for patients whose cancer has not responded to previous treatments, providing a new option for those with anthracycline- and taxane-refractory metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eribulin mesylate (Halaven) for breast cancer. [2016]

Epirubicin, when used in combination with cyclophosphamide and 5-fluorouracil for adjuvant chemotherapy in 10 patients with Stage 2 breast cancer, showed a manageable toxicity profile, primarily causing moderate granulocytopenia without any cases of granulocytopenic fever.

While some patients experienced significant side effects like vomiting and hair loss, the absence of severe cardiac issues suggests that epirubicin may be less cardiotoxic than doxorubicin, indicating its potential for further evaluation in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of adjuvant chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil (CEF) for stage II breast cancer. Jones, SE., Mennel, RG., Peters, GN., et al.[2019]

The combination of eribulin and cyclophosphamide showed a clinical benefit rate of 79.5% in 44 patients with advanced breast cancer, indicating it is an effective treatment option for heavily pretreated individuals.

While the treatment was generally well-tolerated, neutropenia was the most common severe side effect, affecting 47.7% of patients, highlighting the need for monitoring blood cell counts during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib/II study of eribulin in combination with cyclophosphamide in patients with advanced breast cancer. Gumusay, O., Huppert, LA., Magbanua, MJM., et al.[2023]

Eribulin, a microtubule dynamics inhibitor, has been approved for treating locally advanced or metastatic breast cancer in patients who have already undergone at least two chemotherapy regimens, showing a median overall survival increase from 10.6 months to 13.2 months compared to control.

The recommended dosing regimen for eribulin is 1.23 mg/m² administered intravenously on days 1 and 8 of a 3-week cycle, with common side effects including fatigue and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European medicines agency review of eribulin for the treatment of patients with locally advanced or metastatic breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. Pean, E., Klaar, S., Berglund, EG., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4105484/

Comparison of Doxorubicin and Cyclophosphamide Versus ... National Surgical Adjuvant Breast and Bowel Project trial B-15 showed that the four cycles of cyclophosphamide and doxorubicin (AC) was equivalent to six cycles ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e12662

Real life comparison between doxorubicin and ... The dose-dense (dd) regimen demonstrated improved survival regardless of hormone receptor expression or HER2 status.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419356364

Long-term outcomes after adjuvant treatment of sequential ... This 10-year analysis of the BCIRG-005 trial confirmed that the efficacy of TAC was not superior to AC → T in women with node-positive early breast cancer.

4. asco.org asco.org/abstracts-presentations/ABSTRACT186742

Network meta-analysis of adjuvant chemotherapy in early ... Survival outcomes among DDAC-T, ACwkT, TAC, and TC were comparable. DDAC-T survival outcomes were marginally better than the other regimens. Conclusions: DDAC-T ...

5. lbbc.org lbbc.org/about-breast-cancer/treatments/chemotherapy/common-regimens/ac-adriamycin-cyclophosphamide

AC Chemotherapy Regimen Both doxorubicin and cyclophosphamide damage the DNA inside cancer cells so they can't divide, which causes them to die. Doxorubicin stops damaged cancer cells ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12482238/

Neoadjuvant therapy with eribulin, doxorubicin and ... Biological subtype, treatment response and outcomes in inflammatory breast cancer using data from the National Cancer Database. Br J Surg ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842821001633

Comparative effectiveness and safety of eribulin in ... Eribulin significantly increased overall survival in all included MBC patients. · Eribulin also significantly increased overall survival as third/later line ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01328249

Study Details | NCT01328249 | Dose Dense Doxorubucin ... The purpose of this study is to assess the feasibility of dose-dense doxorubicin and cyclophosphamide followed by eribulin mesylate for adjuvant treatment of ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3846767/

Eribulin (Halaven): a new, effective treatment for women ... In women with heavily pretreated breast cancer, eribulin has consistently demonstrated an objective, independently confirmed response rate of 10% and a clinical ...

10. aacrjournals.org aacrjournals.org/cancerres/article/72/24_Supplement/P1-13-11/576365/Abstract-P1-13-11-Adjuvant-treatment-of-early

Adjuvant treatment of early-stage breast cancer with eribulin ... Results: As of 5/22/12, 46 of 80 planned pts have been treated; 38 pts have had ≥1 dose of eribulin and are evaluable for eribulin-related ...