Unesbulin for Leiomyosarcoma

(SUNRISELMS Trial)

Recruiting at 56 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: PTC Therapeutics

Must not be taking: Temozolomide, Dacarbazine

Disqualifiers: Active infection, Gastrointestinal disease, others

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

Compensation: Varies

Number of Visits: 3

Duration: Up to approximately 2 years

360 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug combination of unesbulin and dacarbazine in patients with advanced LMS who have not responded to previous treatments. The goal is to see if unesbulin can help stop cancer growth and make dacarbazine more effective. Dacarbazine is an anticancer drug that has been used to treat various types of cancers.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot have received any other systemic anticancer therapy or radiation within 3 weeks before starting the study treatment.

What data supports the effectiveness of the drug Unesbulin for treating leiomyosarcoma?

The combination of dacarbazine (DTIC) with other drugs has shown some effectiveness in treating leiomyosarcoma, with response rates ranging from 18.4% to 33% in different studies. However, these studies did not specifically evaluate Unesbulin, and the effectiveness of Unesbulin itself for leiomyosarcoma is not directly supported by the provided data. ^{1 2 3 4 5}

What safety data exists for Unesbulin or related treatments in humans?

Dacarbazine, a related treatment, has been evaluated for safety in several studies involving patients with leiomyosarcoma. These studies suggest that dacarbazine is generally safe for use in humans, although specific side effects or safety concerns were not detailed in the provided abstracts. ^{5 6 7 8 9}

How is the drug Unesbulin for leiomyosarcoma different from other treatments?

Unesbulin, combined with dacarbazine, is being studied for its potential effectiveness in treating leiomyosarcoma, a type of cancer that has been resistant to many treatments. This combination is unique because it includes Unesbulin, which is not commonly used in standard treatments for this condition, potentially offering a new approach to managing the disease. ^{1 2 3 5 6}

Research Team

Mark Rance, MD

Principal Investigator

PTC Therapeutics

Eligibility Criteria

This trial is for adults with advanced Leiomyosarcoma (LMS) who have tried at least one other treatment. They should not have had major surgery or certain cancer treatments in the last few weeks and must be mostly recovered from previous therapy side effects, except hair loss. People with well-controlled breathing issues or liver metastases can join, but those with recent serious injuries, certain past cancers, or conditions that could affect drug absorption cannot.

Inclusion Criteria

My asthma or COPD is well-managed.

My cancer has spread to my liver.

I have had at least one treatment for LMS, including drugs like doxorubicin.

Exclusion Criteria

I haven't had cancer treatment or radiation in the last 3 weeks.

I have recovered from major surgery or serious injury within the last 4 weeks.

I don't have stomach issues affecting drug absorption.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive unesbulin plus dacarbazine or placebo plus dacarbazine in 3-week cycles

Up to approximately 2 years

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dacarbazine
• Placebo
• Unesbulin

Trial Overview The study tests Unesbulin combined with Dacarbazine against a placebo plus Dacarbazine in patients whose LMS cannot be surgically removed or has spread and did not respond to prior treatments. The goal is to see if Unesbulin helps better than no active treatment when both are given alongside Dacarbazine.

Participant Groups

Group I: Unesbulin and Dacarbazine Experimental Treatment 2 Interventions

Participants will receive unesbulin 300 milligrams (mg) tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/meter squared (m\^2) intravenously (IV) once every 21 days. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.

Group II: Placebo and Dacarbazine Placebo Group 2 Interventions

Participants will receive placebo matching to unesbulin tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/m\^2 IV once every 21 days. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.

Dacarbazine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Dacarbazine for:

• Hodgkin lymphoma
• Melanoma
• Soft tissue sarcoma

Approved in European Union as Dacarbazine for:

• Hodgkin lymphoma
• Melanoma
• Soft tissue sarcoma

Approved in Canada as Dacarbazine for:

• Hodgkin lymphoma
• Melanoma
• Soft tissue sarcoma

Who Is Running the Clinical Trial?

PTC Therapeutics

Lead Sponsor

Trials

75

Recruited

6,300+

Dr. Matthew B. Klein

PTC Therapeutics

Chief Executive Officer since 2023

BA from the University of Pennsylvania, MD from Yale University School of Medicine, MS in Epidemiology from the University of Washington School of Public Health

Dr. Stuart W. Peltz

PTC Therapeutics

Chief Medical Officer since 2023

MD from Harvard Medical School

Findings from Research

The combination treatment of DMAP (dacarbazine, mitomycin, doxorubicin, and cisplatin) with sargramostim resulted in a 27.8% response rate in patients with advanced uterine leiomyosarcoma, indicating some efficacy in this challenging condition.

However, the treatment was associated with significant toxicity, including high rates of neutropenia (78%) and thrombocytopenia (94%), which led to the decision to close the study after the first stage due to safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of dacarbazine, mitomycin, doxorubicin, and cisplatin with sargramostim in uterine leiomyosarcoma: a Gynecologic Oncology Group study. Long, HJ., Blessing, JA., Sorosky, J.[2017]

The patient-derived orthotopic xenograft (PDOX) mouse model was developed to test treatments for leiomyosarcoma, a rare and difficult-to-treat cancer, using a tumor from a patient's thigh.

In this study, the combination of gemcitabine and docetaxel, trabectedin, and temozolomide were found to be highly effective against leiomyosarcoma, while the commonly used first-line treatment, doxorubicin, was ineffective, highlighting the PDOX model's ability to identify effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A patient-derived orthotopic xenograft (PDOX) nude-mouse model precisely identifies effective and ineffective therapies for recurrent leiomyosarcoma. Zhang, Z., Hu, K., Kiyuna, T., et al.[2020]

References

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

Doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, or doxorubicin alone as a first-line treatment for advanced leiomyosarcoma: A propensity score matching analysis from the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. [2021]

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

A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. [2022]

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

Combination chemotherapy with hydroxyurea, dacarbazine (DTIC), and etoposide in the treatment of uterine leiomyosarcoma: a Gynecologic Oncology Group study. [2019]

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

Doxorubicin, dacarbazine, vincristine, and cyclophosphamide in the treatment of advanced gastrointestinal leiomyosarcoma. [2015]

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

Phase II trial of dacarbazine, mitomycin, doxorubicin, and cisplatin with sargramostim in uterine leiomyosarcoma: a Gynecologic Oncology Group study. [2017]

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

Molecular Biomarkers of Response to Eribulin in Patients with Leiomyosarcoma. [2022]

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

Eribulin versus dacarbazine in patients with leiomyosarcoma: subgroup analysis from a phase 3, open-label, randomised study. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

A patient-derived orthotopic xenograft (PDOX) nude-mouse model precisely identifies effective and ineffective therapies for recurrent leiomyosarcoma. [2020]

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

Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. [2022]