Zanzalintinib for Leiomyosarcoma

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: Anticoagulants, Platelet inhibitors, Herbal supplements

Disqualifiers: Brain metastases, Uncontrolled hypertension, Active infection, others

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

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

Compensation: Varies

Number of Visits: 31

Duration: Up to 6 months

29 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well zanzalintinib (XL092) works in treating patients with leiomyosarcoma that has spread from where it first started to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). Leiomyosarcomas are a type sarcoma that can occur in any location in the body, such as the uterus or in the abdomen. Current standard treatment for leiomyosarcoma only shows a progression-free survival of 4-6 months. XL092, a tyrosine kinase inhibitor, interferes with cell communication and growth and may prevent tumor growth. Giving XL092 may kill more tumor cells in patients with metastatic or unresectable leiomyosarcoma.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot take certain medications like small-molecule kinase inhibitors within 14 days before starting the trial. You also need to stop taking oral anticoagulants at least 3 days before the trial. It's best to discuss your specific medications with the trial team.

What makes the drug Zanzalintinib unique for treating leiomyosarcoma?

Zanzalintinib (XL092) is a novel treatment option for leiomyosarcoma, a condition with limited effective therapies. Unlike traditional treatments that often rely on cytotoxic agents like doxorubicin, Zanzalintinib may offer a new mechanism of action, potentially addressing the unmet medical need for more effective systemic therapies in this challenging condition. ^{1 2 3 4 5}

Research Team

Seth M. Pollack

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for patients with leiomyosarcoma, a type of sarcoma that has spread or can't be removed by surgery. Participants must meet certain health conditions to join, but specific inclusion and exclusion criteria are not provided in the given information.

Inclusion Criteria

I've had more than 2 cancer treatments, but no more than 2 were tyrosine kinase inhibitors.

I am fully active or restricted in physically strenuous activity but can do light work.

Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

Exclusion Criteria

I haven't taken any kinase inhibitor medication in the last 14 days.

I have had more than two prior treatments with tyrosine kinase inhibitors.

I am receiving ongoing treatment for side effects from previous radiation therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive XL092 orally once daily on days 1-14 of each cycle, with cycles repeating every 14 days

Up to 6 months

Bi-weekly visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 5 years

Follow-up at 30 days, then every 12 weeks for 2 years, followed by every 6 months

Treatment Details

Interventions

• Zanzalintinib (XL092)

Trial Overview The trial is testing XL092 (Zanzalintinib), which may interfere with tumor growth in metastatic or unresectable leiomyosarcoma. It's a phase II study to see if this drug can improve survival compared to current treatments.

Participant Groups

Group I: Treatment (XL092) Experimental Treatment 5 Interventions

Patients receive XL092 PO QD on days 1-14 of each cycle. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA at screening and then as clinically indicated, and blood sample collection on study and CT throughout the study.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a Phase II study involving 21 patients with recurrent uterine leiomyosarcoma, alisertib showed no objective tumor responses, indicating it may not be an effective treatment for this condition.

The study found that while 38.1% of patients had stable disease, the event-free survival rate at 6 months was 0%, suggesting that alisertib does not provide meaningful clinical benefit as a single agent in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 study of alisertib (MLN8237) in recurrent or persistent uterine leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group study 0231D. Hyman, DM., Sill, MW., Lankes, HA., et al.[2021]

Research on treating leiomyosarcoma (LMS) is limited, highlighting a need for more effective therapies.

This report presents a case where a patient with recurrent LMS experienced disease regression after treatment with pembrolizumab and lenvatinib, suggesting potential efficacy for this combination therapy in LMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of pembrolizumab and lenvatinib as an alterntive therapy for leiomyosarcoma. Mehta, N., Lee, SS., Salame, G.[2023]

Leiomyosarcoma, a common type of soft tissue sarcoma, accounts for about 20% of sarcomas and is associated with a high rate of metastasis, highlighting the urgent need for effective systemic therapies.

Current conventional treatments for advanced or metastatic leiomyosarcoma show poor efficacy and prognosis, indicating a significant gap in effective treatment options and the necessity for well-designed clinical studies to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What Clinical Trials Are Needed for Treatment of Leiomyosarcoma? Kasper, B., D'Ambrosio, L., Davis, EJ., et al.[2022]

A case report highlights the treatment of a woman in her late 50s with metastatic leiomyosarcoma (LMS) that had a high tumor mutational burden (TMB) using pembrolizumab, an immunotherapy drug.

This case suggests that patients with LMS and high TMB may respond differently to immunotherapy, which has generally been ineffective for most sarcoma patients, indicating a potential new avenue for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 Inhibition in metastatic high tumour mutational burden (TMB) leiomyosarcoma with clinicopathological correlates. Pandita, D., Dave, M., Schulte, B.[2023]

The ATR kinase inhibitor BAY1895344 showed significant effectiveness in inhibiting tumor growth and prolonging survival in patient-derived xenograft models of uterine leiomyosarcoma (uLMS) with ATRX mutations, with median survival increasing from 12.5 to 42 days for one model and from 33 to 60 days for another.

Treatment with BAY1895344 did not result in significant toxicity, indicating a favorable safety profile, which supports the need for clinical trials in uLMS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Harold, J., Bellone, S., Manavella, DD., et al.[2023]

References

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

A phase 2 study of alisertib (MLN8237) in recurrent or persistent uterine leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group study 0231D. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A case of pembrolizumab and lenvatinib as an alterntive therapy for leiomyosarcoma. [2023]

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

What Clinical Trials Are Needed for Treatment of Leiomyosarcoma? [2022]

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

PD-1 Inhibition in metastatic high tumour mutational burden (TMB) leiomyosarcoma with clinicopathological correlates. [2023]

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

Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. [2023]