Zanzalintinib + Eribulin for Soft Tissue Sarcoma

Overseen By Mia C Weiss, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Oral anticoagulants, CYP inhibitors

Disqualifiers: Untreated brain metastases, Uncontrolled hypertension, Active infection, others

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

Compensation: Varies

Number of Visits: 1

Duration: 24 months

18 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators hypothesize that the combination of eribulin and zanzalintinib will be tolerable and lead to improved progression-free survival (PFS) as compared to eribulin alone based on historical data.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications like oral anticoagulants, some complementary medicines, or certain investigational agents close to the start of the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Zanzalintinib + Eribulin for treating soft tissue sarcoma?

Eribulin has shown effectiveness in treating advanced liposarcoma, a type of soft tissue sarcoma, by improving overall survival compared to another drug, dacarbazine. It is approved for use in patients with advanced liposarcoma who have previously received certain chemotherapy treatments. ^{1 2 3 4 5}

What safety data exists for Eribulin in treating soft tissue sarcoma?

Eribulin has been studied for safety in patients with soft tissue sarcoma, and it is approved for use in Japan for all subtypes of this cancer. Studies have shown it to be generally safe, although specific safety data for rare subtypes is limited. ^{2 6 7 8 9}

How does the drug combination of Zanzalintinib and Eribulin differ from other treatments for soft tissue sarcoma?

The combination of Zanzalintinib and Eribulin is unique because Eribulin works by inhibiting microtubule dynamics, which is different from other drugs targeting tubulin, and it has shown effectiveness in certain soft tissue sarcomas. Combining it with Zanzalintinib, which may target different pathways, could enhance its antitumor effects, offering a novel approach compared to existing treatments. ^{4 6 7 10 11}

Research Team

Mia C Weiss, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Adults with advanced liposarcoma or leiomyosarcoma who have measurable disease, good performance status, and adequate organ function. They must have tried at least one prior therapy but no more than two. Participants need to use effective contraception and cannot be pregnant or breastfeeding. Those with certain serious health conditions, recent major cardiovascular events, uncontrolled illnesses, or allergies to study drugs are excluded.

Inclusion Criteria

Measurable disease per RECIST 1.1

I am fully active or have some restrictions but can still carry out light work.

I agree to use birth control during and after the study as required.

Exclusion Criteria

Currently receiving any other investigational agents

I have been treated with zanzalintinib before.

I haven't had cancer treatment in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanzalintinib and eribulin in 21-day cycles, with dose escalation to determine the maximum tolerated dose

24 months

Visits on Days 1 and 8 of each 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 years

Treatment Details

Interventions

• Eribulin
• Zanzalintinib

Trial Overview The trial is testing the combination of Zanzalintinib and Eribulin versus Eribulin alone in patients with specific sarcomas. The goal is to see if this drug combo can extend the time patients live without their disease getting worse compared to historical data on Eribulin only.

Participant Groups

Group I: Dose Level 3: Zanzalintinib + Eribulin Experimental Treatment 2 Interventions

Patients will receive zanzalintinib 100 mg by mouth once daily on Days 1 through 21 and eribulin intravenously on Days 1 and 8 of a 21-day cycle.

Group II: Dose Level 2: Zanzalintinib + Eribulin Experimental Treatment 2 Interventions

Patients will receive zanzalintinib 80 mg by mouth once daily on Days 1 through 21 and eribulin intravenously on Days 1 and 8 of a 21-day cycle.

Group III: Dose Level 1 (starting dose): Zanzalintinib + Eribulin Experimental Treatment 2 Interventions

Patients will receive zanzalintinib 60 mg by mouth once daily on Days 1 through 21 and eribulin intravenously on Days 1 and 8 of a 21-day cycle.

Group IV: Dose Level -1: Zanzalintinib + Eribulin Experimental Treatment 2 Interventions

Patients will receive zanzalintinib 40 mg by mouth once daily on Days 1 through 21 and eribulin intravenously on Days 1 and 8 of a 21-day cycle.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

References

1. England pubmed.ncbi.nlm.nih.gov

Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Eribulin in the management of inoperable soft-tissue sarcoma: patient selection and survival. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The clinical outcome of eribulin treatment in Japanese patients with advanced soft tissue sarcoma: a Tokai Musculoskeletal Oncology Consortium study. [2020]

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

Eribulin activity in soft tissue sarcoma monolayer and three-dimensional cell line models: could the combination with other drugs improve its antitumoral effect? [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of eribulin mesylate in advanced soft tissue sarcomas. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Interim results of a real-world observational study of eribulin in soft tissue sarcoma including rare subtypes. [2022]

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

Activity of eribulin mesylate in patients with soft-tissue sarcoma: a phase 2 study in four independent histological subtypes. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Phase 2 study of eribulin in patients with previously treated advanced or metastatic soft tissue sarcoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of eribulin in Japanese patients with soft tissue sarcoma including rare subtypes: a post-marketing observational study. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Eribulin in Soft Tissue Sarcomas. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Combination of eribulin plus AKT inhibitor evokes synergistic cytotoxicity in soft tissue sarcoma cells. [2021]