SDX-7320 + Eribulin for Breast Cancer

Recruiting at 9 trial locations

Overseen By Sherry Shen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Antihyperglycemics, QT-prolonging drugs

Disqualifiers: Diabetes, CNS pathology, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for triple-negative breast cancer (TNBC) by combining the study drug SDX-7320 (Evexomostat) with standard chemotherapy, eribulin (Halaven). Researchers aim to determine if this combination is more effective and safe than using eribulin alone. The trial targets individuals with TNBC and metabolic issues, such as high blood sugar or a high body mass index (BMI), who have undergone some treatments but not more than two. Those with TNBC, metabolic dysfunction, and limited prior treatments may find this trial suitable. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, contributing to advancements in TNBC treatment.

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

The trial protocol does not specify if you must stop all current medications. However, you cannot take medications that prolong the QT interval or induce Torsade de Pointes, and you must stop these 7 days before starting the trial. Herbal preparations are also not allowed, except for cannabinoids and CBD compounds.

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

Research shows that SDX-7320, combined with the chemotherapy drug eribulin, is under study for its safety and effectiveness in treating breast cancer. Earlier studies have assessed the safety of SDX-7320 in patients with advanced cancer, suggesting that the treatment is generally well-tolerated, with most side effects being mild or moderate.

Eribulin is already approved for breast cancer treatment, and its safety profile is well-known. Common side effects include tiredness, hair loss, and nausea, which can usually be managed with medical help.

The current study includes a safety run-in period, where researchers first monitor a small group of participants closely for any side effects before adding more people. While some side effects are expected, the treatment aims to be as safe as possible. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about SDX-7320 combined with Eribulin because this new combination targets breast cancer differently. While Eribulin is a chemotherapy drug that disrupts cancer cell division, SDX-7320 is designed to inhibit a protein called PAK4, which is involved in cancer cell growth and spread. This dual approach could potentially enhance the effectiveness of treatment by not only attacking cancer cells directly but also disrupting the pathways they use to grow. Unlike standard treatments that typically focus on one mechanism, this combination offers a more comprehensive attack on the cancer, which might lead to better outcomes for patients.

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

Research has shown that combining SDX-7320 with Eribulin could effectively treat breast cancer, particularly types with metabolic issues like triple-negative breast cancer (TNBC). In this trial, some participants will receive SDX-7320 plus Eribulin, while others will receive Eribulin plus a placebo. Studies suggest that this combination may help prevent insulin resistance and improve tumor response to treatment. Early findings indicate improvements in factors related to blood vessel growth and metabolism, which are crucial for controlling tumors. Eribulin, a standard chemotherapy for breast cancer, works by stopping cancer cells from dividing. Adding SDX-7320 might enhance its effectiveness by targeting the metabolic processes that aid tumor growth. ^{1 2 5 6 7}

Who Is on the Research Team?

Sherry Shen, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with triple-negative metastatic breast cancer who have metabolic dysfunction (HbA1c > 5.5 or BMI ≥ 30), previously treated with anthracycline and taxane, and suitable for eribulin therapy. Participants must not have had more than two prior therapies for advanced cancer, no severe heart issues, uncontrolled HIV, known allergies to the drugs tested, underweight conditions (BMI < 18.5), brain malignancies or active CNS pathology.

Inclusion Criteria

I am willing and able to follow the study's requirements, including fasting before treatment.

My cancer can be measured by scans or I have a specific type of bone lesion.

If sexually active female of childbearing potential, willing to use a contraception method listed

Exclusion Criteria

My liver disease is moderately to severely advanced.

Any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, contraindicate patient participation in the clinical study

I have type 1 diabetes or type 2 diabetes that requires insulin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

The first 15 patients enrolled will receive SDX-7320 in combination with eribulin to confirm safety

4-6 weeks

Treatment

Participants receive either SDX-7320 plus eribulin or placebo plus eribulin

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Eribulin
• Placebo
• SDX-7320

Trial Overview The study tests SDX-7320 combined with standard chemotherapy drug eribulin against eribulin alone in treating breast cancer patients with metabolic dysfunction. The goal is to assess effectiveness and safety of this combination treatment compared to the standard therapy.

How Is the Trial Designed?

Group I: SDX-7320 plus Eribulin (safety run-in period) Experimental Treatment 2 Interventions

During the safety run-in period, the first 15 patients enrolled will be assigned to received study drug SDX-7320 plus Eribulin. Not randomized.

Group II: SDX-7320 plus Eribulin Experimental Treatment 2 Interventions

Patients randomized to SDX-7320 plus Eribulin.

Group III: Eribulin Plus Placebo Placebo Group 2 Interventions

Patients randomized to the control arm will receive placebo plus Eribulin.

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

Approved in European Union as Halaven for:

• Locally advanced or metastatic breast cancer

Approved in United States as Halaven for:

• Metastatic breast cancer
• Liposarcoma

Approved in Japan as Halaven for:

• Breast cancer
• Soft tissue sarcoma

Approved in Canada as Halaven for:

• Metastatic breast cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

SynDevRx, Inc.

Industry Sponsor

Trials

3

Recruited

140+

Published Research Related to This Trial

Eribulin, a synthetic analog of the tubulin inhibitor halichondrin B, is being developed by Eisai Co Ltd as a potential cancer treatment, currently undergoing Phase III trials for breast cancer in the US and Europe.

In addition to breast cancer, eribulin is also in various stages of clinical trials for multiple other cancers, including non-small cell lung cancer (NSCLC) and soft tissue sarcoma, indicating its broad potential application in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eribulin, a simplified ketone analog of the tubulin inhibitor halichondrin B, for the potential treatment of cancer. Newman, S.[2019]

Eribulin demonstrates broad-spectrum antitumor activity against various human cancer types in preclinical models, showing significant tumor growth inhibition and even regression in some cases.

The study suggests that moderately intermittent dosing schedules (like the approved clinical schedule of days 1 and 8 of a 21-day cycle) provide optimal effectiveness and tolerability for eribulin treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Broad spectrum preclinical antitumor activity of eribulin (Halaven(R)): optimal effectiveness under intermittent dosing conditions. Towle, MJ., Nomoto, K., Asano, M., et al.[2016]

In a phase II study involving 103 heavily pretreated metastatic breast cancer patients, eribulin mesylate showed an objective response rate of 11.5% and a clinical benefit rate of 17.2%, indicating its efficacy in this challenging population.

Eribulin was generally well-tolerated, with manageable side effects; the most common severe toxicities included neutropenia (64%) and leukopenia (18%), but there were infrequent cases of neuropathy, suggesting a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of eribulin mesylate, a halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. Vahdat, LT., Pruitt, B., Fabian, CJ., et al.[2022]

Eribulin mesylate (ERI) demonstrated statistically longer overall survival compared to treatment by physician's choice and a combination of gemcitabine and vinorelbine in patients with metastatic breast cancer, based on a network meta-analysis of seven trials.

In patients with triple negative breast cancer, ERI also showed a significant overall survival benefit compared to capecitabine, highlighting its potential as an effective treatment option in this specific subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Network meta-analysis of eribulin versus other chemotherapies used as second- or later-line treatment in locally advanced or metastatic breast cancer. Zhao, Q., Hughes, R., Neupane, B., et al.[2021]

Eribulin mesylate is an effective treatment for metastatic breast cancer in patients who have already undergone at least two prior chemotherapy regimens, showing significant improvements in overall and progression-free survival in Phase III clinical trials.

This novel synthetic agent works by binding to the microtubule cap and inhibiting tubulin polymerization, leading to microtubule arrest, and has a manageable safety profile with low rates of peripheral neuropathy, primarily causing neutropenia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eribulin mesylate: a novel halichondrin B analogue for the treatment of metastatic breast cancer. McBride, A., Butler, SK.[2022]

The combination of eribulin and S-1 was evaluated in 12 metastatic breast cancer patients, with the recommended dose for phase II trials set at eribulin 1.4 mg/m² and S-1 65 mg/m², after observing dose-limiting toxicity at higher doses.

Preliminary results showed that 41.7% of patients with measurable disease experienced a partial response, indicating potential anticancer activity that merits further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose-escalation study of eribulin and S-1 for metastatic breast cancer. Sakiyama, T., Tsurutani, J., Iwasa, T., et al.[2018]

Eribulin is an effective treatment for patients with advanced or metastatic breast cancer who have previously been treated with anthracyclines and taxanes, as shown by analyses from large Phase III clinical trials.

The drug works through both mitotic and nonmitotic mechanisms, and ongoing studies are exploring its use in combination with immunotherapies, which could enhance treatment options for aggressive breast cancer cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives on the mechanism of action and clinical application of eribulin for metastatic breast cancer. O'Shaughnessy, J., Kaklamani, V., Kalinsky, K.[2019]

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]

In a study of 48 patients with metastatic breast cancer treated with eribulin, the drug was found to be safe and well tolerated, with no hypersensitivity reactions or toxic deaths reported.

Approximately 48% of patients experienced a clinical benefit, with one patient achieving complete remission and 33.3% showing a partial response, indicating that eribulin can be effective even in heavily pretreated individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective safety and efficacy analysis of the first patients treated with eribulin for metastatic breast cancer in Stockholm, Sweden. Kessler, L., Falato, C., Margolin, S., et al.[2022]

Eribulin is an effective treatment option for patients with metastatic breast cancer who have not responded to other chemotherapy drugs, such as anthracyclines and taxanes, as it induces cancer cell death by disrupting microtubule growth.

While eribulin can be life-saving, it is associated with side effects like neutropenia, neuropathy, and QT prolongation, and ongoing trials are exploring its efficacy in other types of cancers, indicating its potential for broader applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eribulin drug review. Shetty, N., Gupta, S.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05570253

NCT05570253 | A Study of SDX-7320 in Combination With ... The researchers are doing this study to find out whether the study drug, SDX-7320, when combined with the standard chemotherapy eribulin, is an effective ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS1131

The ARETHA study: A phase 2 randomized control trial ... The goal of this phase 2 study is to test whether evexomostat prevents worsening of insulin resistance and augments tumor response in patients with metastatic ...

3. aacrjournals.org aacrjournals.org/cancerres/article/83/5_Supplement/OT2-17-02/717517/Abstract-OT2-17-02-The-ARETHA-Study-A-phase-2

The ARETHA Study: A phase 2 randomized control trial of ... The goal of this phase 2 study is to test whether evexomostat in combination with eribulin chemotherapy prevents worsening of insulin resistance ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12183619/

A Phase 1 Safety Study of Evexomostat (SDX-7320) in ... Improvements were observed in angiogenic and metabolic biomarkers. Significance: Obesity and insulin resistance are known to promote tumor ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-08559

A Study of SDX-7320 in Combination with Eribulin for ... Giving evexomostat in combination with eribulin may be more effective at treating metastatic TNBC than standard chemotherapy on its own. Eligibility Criteria ...

6. aacrjournals.org aacrjournals.org/cancerrescommun/article/5/6/1008/763101/A-Phase-1-Safety-Study-of-Evexomostat-SDX-7320-in

A Phase 1 Safety Study of Evexomostat (SDX-7320) in ... To investigate the safety and tolerability of evexomostat (SDX-7320) in patients with late-stage cancer. Patients and Methods:.

7. clinicaltrial.be clinicaltrial.be/en/details/22494?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

A Study of SDX-7320 in Combination With Eribulin for Peop... The study includes a safety run-in period in which the first 15 patients enrolled will be assigned to receive the study drug SDX-7320 in ...