Tolinapant + Eribulin for Breast Cancer

Recruiting at 2 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Neuropathy, Infections, Hypertension, others

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

Compensation: Varies

Number of Visits: 2

Duration: 28 days per cycle

42 Participants Needed

Trial Summary

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

The trial does not specify if you need to stop all current medications, but you must stop using any medication that is a moderate or strong CYP3A4 inhibitor or inducer at least 2 weeks before starting the study.

What data supports the effectiveness of the drug combination Tolinapant + Eribulin for breast cancer?

Eribulin mesylate (Halaven) is approved for treating metastatic breast cancer in patients who have already tried at least two other chemotherapy treatments, showing it can be effective in difficult-to-treat cases. ^{1 2 3 4 5}

Is the combination of Tolinapant and Eribulin safe for humans?

Eribulin, also known as Halaven, has been used in treating advanced breast cancer and is generally considered safe, but common side effects include tiredness and low white blood cell counts. There is no specific safety data available for the combination of Tolinapant and Eribulin. ^{1 2 3 5 6}

How is the drug Tolinapant + Eribulin unique for breast cancer treatment?

The combination of Tolinapant and Eribulin is unique because Eribulin is a non-taxane microtubule dynamics inhibitor, which has shown effectiveness in treating metastatic breast cancer with a lower risk of causing peripheral neuropathy (nerve damage) compared to other similar drugs like paclitaxel. ^{1 2 3 7 8}

What is the purpose of this trial?

This phase I/Ib trial tests the safety, side effects, best dose, and effectiveness of ASTX660 (tolinapant) in combination with eribulin mesylate (eribulin) in treating patients with triple negative breast cancer that cannot be removed by surgery (unresectable) or that has spread to nearby tissues or lymph nodes (locally advanced) or to other places in the body (metastatic). Tolinapant may stop the growth of tumor cells by blocking proteins, such as XIAP and cIAP1, needed for tumor cell survival. Chemotherapy drugs, such as eribulin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving tolinapant in combination with eribulin may be safe, tolerable, and/or effective in treating patients with unresectable, locally advanced, or metastatic triple negative breast cancer.

Research Team

Kristen Kelley

Principal Investigator

Ohio State University Comprehensive Cancer Center LAO

Eligibility Criteria

This trial is for adults with advanced triple negative breast cancer that can't be surgically removed or has spread. Participants must have tried at least two systemic treatments, have measurable disease by certain criteria, and meet specific blood cell count requirements.

Inclusion Criteria

My cancer can be measured by standard health guidelines.

I can do most activities, but may need help.

My cancer is advanced and cannot be removed by surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tolinapant orally once daily on days 1-7 and 15-21 and eribulin intravenously on days 1 and 15 of each 28-day cycle

28 days per cycle

2 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 months

Treatment Details

Interventions

• ASTX660 (Tolinapant)
• Eribulin Mesylate

Trial Overview The trial tests the safety and effectiveness of ASTX660 (tolinapant) combined with usual chemotherapy drug eribulin in patients with unresectable or metastatic triple negative breast cancer. It aims to find the best dose and see if this combination helps stop tumor growth.

Participant Groups

Group I: Treatment (tolinapant, eribulin) Experimental Treatment 7 Interventions

Patients receive tolinapant PO QD on days 1-7 and 15-21 and eribulin IV over 2-5 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, tissue biopsy, chest X-ray, and CT or MRI throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

In a phase II study involving 66 patients with advanced non-small cell lung cancer (NSCLC) previously treated with taxanes, eribulin mesylate showed a modest objective response rate of 5%, with a median duration of response lasting 7.8 months, particularly in taxane-sensitive patients.

Eribulin was well tolerated, with primarily hematologic toxicities and only two cases of grade 3 neuropathy, indicating it may be a safe treatment option for patients with pretreated NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of halichondrin B analog eribulin mesylate (E7389) in patients with advanced non-small cell lung cancer previously treated with a taxane: a California cancer consortium trial. Gitlitz, BJ., Tsao-Wei, DD., Groshen, S., et al.[2022]

Eribulin mesylate is an effective treatment for metastatic breast cancer, showing a median overall survival of 13.1 months compared to 10.6 months with other chemotherapy options, based on a Phase III trial.

In contrast, eribulin did not improve response rates or survival outcomes in patients with head and neck or pancreatic cancers, indicating its efficacy is limited to specific cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eribulin mesylate (E7389): review of efficacy and tolerability in breast, pancreatic, head and neck, and non-small cell lung cancer. Scarpace, SL.[2016]

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]

In a study of 40 elderly women with metastatic breast cancer, Eribulin mesylate demonstrated a median overall survival of 12.8 months and a median progression-free survival of 3.2 months, indicating its efficacy as a treatment option after previous therapies.

Eribulin was well tolerated with a manageable toxicity profile, and it positively impacted the quality of life for patients, suggesting it is a viable chemotherapy option for elderly patients with metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Eribulin mesylate as second-line therapy in elderly patients with HER/2 negative metastatic breast cancer (MBC): efficacy, tolerability and Quality of Life. De Luca, R., Alù, M., Genova, G., et al.[2021]

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 two phase 2 trials involving 108 patients, first-line treatment with eribulin mesylate, either alone or in combination with trastuzumab, showed promising objective response rates of 28.6% and 71.2%, respectively, with median progression-free survival of 6.8 and 11.6 months.

The treatment did not significantly worsen health-related quality of life for most patients, with over 60% reporting stable or improved quality-of-life scores, indicating that eribulin has an acceptable safety profile comparable to other chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life in patients receiving first-line eribulin mesylate with or without trastuzumab for locally recurrent or metastatic breast cancer. Schwartzberg, L., McIntyre, K., Wilks, S., et al.[2020]

In a study comparing the effects of eribulin mesylate and paclitaxel on mice with preexisting paclitaxel-induced peripheral neuropathy (PN), eribulin mesylate did not worsen nerve function, while additional paclitaxel treatment significantly decreased nerve conduction velocity and amplitude.

These findings suggest that eribulin mesylate may be a safer alternative for patients with advanced breast cancer who have experienced PN from previous paclitaxel treatment, potentially allowing for continued chemotherapy without exacerbating nerve damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropathy-inducing effects of eribulin mesylate versus paclitaxel in mice with preexisting neuropathy. Wozniak, KM., Wu, Y., Farah, MH., et al.[2021]

References

1. England 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. [2021]

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

A phase II study of halichondrin B analog eribulin mesylate (E7389) in patients with advanced non-small cell lung cancer previously treated with a taxane: a California cancer consortium trial. [2022]

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

Eribulin mesylate (E7389): review of efficacy and tolerability in breast, pancreatic, head and neck, and non-small cell lung cancer. [2016]

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

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

5. Italy pubmed.ncbi.nlm.nih.gov

Use of Eribulin mesylate as second-line therapy in elderly patients with HER/2 negative metastatic breast cancer (MBC): efficacy, tolerability and Quality of Life. [2021]

6. United States 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. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Health-related quality of life in patients receiving first-line eribulin mesylate with or without trastuzumab for locally recurrent or metastatic breast cancer. [2020]

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

Neuropathy-inducing effects of eribulin mesylate versus paclitaxel in mice with preexisting neuropathy. [2021]