Eribulin + Radiation for Abdominal Cancer

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: OHSU Knight Cancer Institute

Must not be taking: Eribulin, TdP risk drugs

Disqualifiers: Distant metastases, Uncontrolled arrhythmia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 9 weeks

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib trials studies the side effects and best dose of eribulin mesylate when given together with radiation therapy in treating patients with retroperitoneal liposarcoma that can be removed by surgery. Drugs used in chemotherapy, such as eribulin mesylate, 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. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more tumor cells.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require you to stop using herbal supplements unless approved by a study pharmacist. You can continue using marijuana or its derivatives.

What data supports the effectiveness of the treatment Eribulin + Radiation for Abdominal Cancer?

Intensity-modulated radiation therapy (IMRT), a component of the treatment, has shown promise in treating various cancers by precisely targeting tumors while minimizing damage to surrounding healthy tissue. Studies have indicated its effectiveness in prostate cancer and soft tissue sarcomas, suggesting potential benefits for abdominal cancer as well. ^{1 2 3 4 5}

Is intensity-modulated radiation therapy (IMRT) generally safe for humans?

Research on intensity-modulated radiation therapy (IMRT) for various cancers, such as cervical, esophageal, and prostate, shows that it can cause some gastrointestinal and other toxicities, but it is generally considered safe when used appropriately. ^{3 6 7 8 9}

How does the drug eribulin combined with radiation differ from other treatments for abdominal cancer?

Eribulin is unique because it is a non-taxane microtubule inhibitor, which means it works by disrupting the internal structure of cancer cells, preventing them from dividing and growing. This drug has shown effectiveness in other cancers like breast cancer and may offer a novel approach when combined with radiation for abdominal cancer, potentially with fewer side effects like peripheral neuropathy compared to other similar treatments. ^{10 11 12 13 14}

Research Team

Lara Davis, MD

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

This trial is for patients with a specific cancer called retroperitoneal liposarcoma that can be surgically removed. Eligible participants include those with measurable disease, good performance status, adequate organ function, and no prior treatment for this cancer type. They must also agree to use contraception and have no history of certain heart conditions or other cancers within the last 3 years.

Inclusion Criteria

I have been diagnosed with liposarcoma.

Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Subjects of childbearing potential must have a negative urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at time of screening

Exclusion Criteria

I have had treatment for liposarcoma before.

I have previously been treated with eribulin.

I cannot have an MRI due to a pacemaker, severe claustrophobia, allergy to contrast dye, or weighing over 300 lbs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive eribulin mesylate IV and undergo intensity-modulated radiation therapy. Treatment repeats every 21 days for up to 3 cycles.

9 weeks

Multiple visits for IV administration and daily radiation therapy

Surgery

Participants may undergo surgery within 3-10 weeks after radiation therapy.

3-10 weeks post-radiation

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-ups at 2 weeks, 9 weeks, and then every 6 months for 10 years.

10 years

Follow-up visits at specified intervals

Treatment Details

Interventions

• Eribulin Mesylate
• Intensity-Modulated Radiation Therapy

Trial Overview The trial is testing the combination of eribulin mesylate (a chemotherapy drug) with radiation therapy to see how well they work together in treating retroperitoneal liposarcoma. The study will determine the best dose of eribulin when used alongside high-energy x-rays intended to kill tumor cells.

Participant Groups

Group I: Treatment (eribulin mesylate, IMRT, surgery) Experimental Treatment 6 Interventions

Patients receive eribulin mesylate IV over 2-5 minutes on days 1 and 8 and undergo intensity-modulated radiation therapy QD 5 days a week beginning on day 8 of cycle 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may undergo surgery within 3-10 weeks after radiation therapy.

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

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

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Findings from Research

In a study of 20 patients with intermediate-risk prostate cancer receiving hypofractionated radiotherapy (HRT), no acute gastrointestinal (GI) toxicity was observed, highlighting the safety of this treatment approach.

Only one patient (5%) experienced late GI toxicity (grade 3 rectal bleeding) within the first year after treatment, indicating that HRT has minimal long-term effects on rectal mucosa, further supporting its use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and Late Rectal Toxicity Following Hypofractionated Radiotherapy in Patients With Prostate Cancer: Results of a Prospective Study. Kounadis, G., Syrigos, N., Kougioumtzopoulou, A., et al.[2022]

In a study of 59 patients with extremity soft tissue sarcomas, intensity-modulated radiotherapy (IMRT) resulted in late toxicities in 75% of patients, with the majority being mild to moderate (G1-2), including functional limitations and chronic pain.

A larger volume of healthy soft tissue surrounding the treatment area (greater than 3500 cm³) was associated with reduced late toxicities, suggesting that careful planning of radiotherapy can help minimize side effects for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of intensity-modulated radiotherapy toxicity in extremity soft tissue sarcomas patients: A role for irradiated healthy soft tissue volume? Bourdais, R., Achkar, S., Honoré, C., et al.[2022]

Intensity-modulated radiation therapy (IMRT) offers improved dose targeting, which may reduce normal tissue damage compared to traditional radiation methods, making it a promising option in radiation oncology.

While preliminary results for IMRT in treating head and neck and prostate cancers are encouraging, the clinical data is still developing, and the number of patients studied remains relatively small.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy: emerging cancer treatment technology. Hong, TS., Ritter, MA., Tomé, WA., et al.[2018]

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]

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

A retrospective cohort study of low-dose intensity-modulated radiotherapy for unresectable liver metastases. [2021]

2. Greece pubmed.ncbi.nlm.nih.gov

Acute and Late Rectal Toxicity Following Hypofractionated Radiotherapy in Patients With Prostate Cancer: Results of a Prospective Study. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

Prospective evaluation of intensity-modulated radiotherapy toxicity in extremity soft tissue sarcomas patients: A role for irradiated healthy soft tissue volume? [2022]

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

Intensity-modulated radiation therapy: emerging cancer treatment technology. [2018]

5. Thailand pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy combined with endocrine therapy for intermediate and advanced prostate cancer: long-term outcome of Chinese patients. [2019]

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

Duodenal and other gastrointestinal toxicity in cervical and endometrial cancer treated with extended-field intensity modulated radiation therapy to paraaortic lymph nodes. [2013]

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

Long-term clinical outcome of intensity-modulated radiation therapy for locally advanced esophageal squamous cell carcinoma. [2022]

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

Application of vincristine and cisplatin combined with intensity-modulated radiation therapy in the treatment of patients with advanced cervical cancer. [2022]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Whole pelvic intensity-modulated radiotherapy for high-risk prostate cancer: a preliminary report. [2021]

10. 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]

11. 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]

12. England pubmed.ncbi.nlm.nih.gov

Phase I study of the halichondrin B analogue eribulin mesylate in combination with cisplatin in advanced solid tumors. [2018]

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

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

14. Netherlands pubmed.ncbi.nlm.nih.gov

Eribulin -- a review of preclinical and clinical studies. [2023]