Tolinapant + Eribulin for Breast Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, tolinapant (an experimental treatment) and eribulin (a chemotherapy drug), to treat triple negative breast cancer. The goal is to determine the safety and effectiveness of these drugs when used together for breast cancer that cannot be surgically removed or has metastasized. It is open to individuals with this type of breast cancer that has advanced or spread after at least two treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

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.

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

Research has shown that eribulin is generally well-tolerated for treating advanced breast cancer and can extend patient survival. One study found that patients lived an average of 13.1 months with eribulin, compared to 10.6 months with other treatments. Although eribulin is usually safe, it can cause side effects, which are often manageable.

Tolinapant remains under study. Early trials are examining its safety and side effects when used with eribulin. Currently, detailed safety information for tolinapant alone or with eribulin is unavailable. As this combination is in early testing, researchers are still assessing its tolerability. This trial aims to determine if using tolinapant with eribulin is a safe option for patients with advanced breast cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Tolinapant and Eribulin for breast cancer because it offers a new way to tackle the disease. Tolinapant is unique as it targets proteins that help cancer cells evade death, potentially making the cancer more vulnerable to treatment. Eribulin, on the other hand, is a chemotherapy drug known for its ability to disrupt cancer cell division. Together, these treatments might enhance each other's effectiveness, offering hope for better outcomes compared to standard chemotherapy options like anthracyclines or taxanes. This combination could lead to more efficient cancer cell destruction with potentially fewer side effects.

What evidence suggests that the combination of tolinapant and eribulin might be an effective treatment for triple negative breast cancer?

Research has shown that eribulin, one of the drugs in this trial's combination treatment, effectively treats advanced breast cancer. Studies have found that patients using eribulin live an average of 13.1 months, compared to 10.6 months with other treatments. Tolinapant, the other drug in this trial, blocks proteins that help cancer cells survive, potentially stopping the cancer from growing. Combining tolinapant with eribulin, as tested in this trial, could enhance eribulin's effectiveness by further weakening the cancer cells. While this combination is still under study, each drug has shown promise in fighting cancer individually. ^{1 2 6 7 8}

Who Is on the Research Team?

Kristen Kelley

Principal Investigator

Ohio State University Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06590558?term=AREA%5BBasicSearch%5D(ASTX660)&rank=8

Testing the Addition of an Investigational Anti-Cancer Drug ... This phase I/Ib trial tests the safety, side effects, best dose, and effectiveness of ASTX660 (tolinapant) in combination with eribulin mesylate (eribulin) ...

2. withpower.com withpower.com/trial/phase-1-locally-advanced-hormone-receptor-positive-breast-carcinoma-8-2024-5273e

Tolinapant + Eribulin for Breast Cancer · Info for Participants 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 ...

3. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06590558/

Trial | NCT06590558 This phase I/Ib trial tests the safety, side effects, best dose, and effectiveness of ASTX660 (tolinapant) in combination with eribulin mesylate (eribulin) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4243003/

Efficacy of eribulin in women with metastatic breast cancer Despite improvements in treatment, long-term survival for women with advanced breast cancer remains poor, with a 5-year survival rate of less than 25 % for ...

5. media-us.eisai.com media-us.eisai.com/2021-05-18-Eisai-Announces-Real-World-Data-on-the-Effectiveness-of-HALAVEN-R-eribulin-mesylate-for-the-Treatment-of-Patients-with-Metastatic-Breast-Cancer-mBC-Published-in-Advances-in-Therapy

Eisai Announces Real-World Data on the Effectiveness of ... A greater proportion of patients with TNBC were treated with HALAVEN in the 3rd line (87.9%) compared with the overall patient cohort (78%), ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-05666

Testing the Addition of an Investigational Anti-Cancer Drug ... This phase I/Ib trial tests the safety, side effects, best dose, and effectiveness of ASTX660 (tolinapant) in combination with eribulin mesylate (eribulin)

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12179173/

Efficacy and safety of Eribulin-based chemotherapy in HER2 ... It has been demonstrated to significantly extend both progression-free survival (PFS) and overall survival (OS), especially when administered as ...

8. halaven.com halaven.com/hcp/metastatic-breast-cancer/real-world-evidence

Exploratory Analysis Patient Subgroups HALAVEN (eribulin mesylate) Injection is indicated for the treatment of patients with metastatic breast cancer (mBC) who have previously received at least 2 ...