Unesbulin for Leiomyosarcoma

(SUNRISELMS Trial)

No longer recruiting at 62 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with leiomyosarcoma, a cancer of smooth muscle tissue that cannot be surgically removed or has spread. The study compares the effects of the drug unesbulin with a standard treatment, dacarbazine (a chemotherapy drug), to determine if adding unesbulin is more effective than dacarbazine alone. Individuals who have tried at least one other cancer treatment, but whose cancer has returned or did not respond, might be suitable candidates. Participants should not have previously tried dacarbazine or have certain health issues that could interfere with the trial. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

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.

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

Research shows that using unesbulin with dacarbazine appears safe. Studies found that patients tolerated unesbulin at 300 mg twice a week, along with dacarbazine every 21 days, without major safety issues. The combination demonstrated a good balance between benefits and risks. Thus, unesbulin with dacarbazine is relatively safe for people with leiomyosarcoma, a type of soft tissue cancer. However, like any treatment, side effects may occur, so discussing concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leiomyosarcoma?

Most treatments for leiomyosarcoma, like chemotherapy with drugs such as doxorubicin or ifosfamide, work by attacking rapidly dividing cells. However, Unesbulin is unique because it targets a different pathway, potentially disrupting the cancer cells' ability to survive. Researchers are excited about Unesbulin because it offers a novel mechanism that could work alongside traditional chemotherapy (like dacarbazine) to enhance effectiveness. By combining Unesbulin with dacarbazine, there's hope for a more robust attack on the cancer, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for leiomyosarcoma?

In this trial, participants will receive either the combination of unesbulin and dacarbazine or a placebo with dacarbazine. Research has shown that using unesbulin with dacarbazine may help treat leiomyosarcoma, a type of cancer in smooth muscle tissue. In one study, 18.2% of patients taking this combination experienced noticeable tumor shrinkage. Additionally, 51.5% of patients achieved disease control, meaning their cancer stopped growing. This combination has proven more effective at stopping tumor growth than using either drug alone. These findings suggest that unesbulin with dacarbazine could be a helpful treatment option for this condition. ^{1 2 4 6 7}

Who Is on the Research Team?

Mark Rance, MD

Principal Investigator

PTC Therapeutics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38684039/

Phase Ib Study of Unesbulin (PTC596) Plus Dacarbazine ...

Unesbulin 300 mg twice per week plus DTIC 1000 mg/m 2 once every 21 days was identified as the RP2D, demonstrating a favorable benefit-risk ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.23.01684

Phase Ib Study of Unesbulin (PTC596) Plus Dacarbazine ...

The antitumor efficacy of unesbulin as a single agent and in combination with other standard-of-care anticancer agents, including dacarbazine ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05269355

NCT05269355 | A Study of Unesbulin in Participants With ...

This study will compare the efficacy and safety of unesbulin plus dacarbazine versus placebo plus dacarbazine in participants with unresectable or ...

4.

ir.ptcbio.com

ir.ptcbio.com/news-releases/news-release-details/preliminary-results-presented-asco-demonstrated-promising?mobile=1

Release Details - Investors | PTC Therapeutics, Inc.

The results demonstrated that treated patients achieved an 18.2 percent objective response rate and a 51.5 percent disease control rate.

5.

hra.nhs.uk

hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/phase-23-study-to-evaluate-efficacy-and-safety-of-unesbulin-in-leiomyosarcoma/

Phase 2/3 Study to Evaluate Efficacy and Safety of ...

The preclinical data of unesbulin in combination with dacarbazine has shown more effective tumour suppression than either drug alone. Approximately 345 ...

6.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.11507

A phase 1b study of unesbulin (PTC596) plus dacarbazine ...

Conclusions: Unesbulin 300 mg BIW in combination with DTIC 1,000 mg/m2 every 21 days was well tolerated and demonstrated promising efficacy in a ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10031121/

Therapeutic advances in leiomyosarcoma - PMC

A Study of Unesbulin in Participants With Advanced Leiomyosarcoma (LMS) (SUNRISELMS) ... Results demonstrated safety and tolerability of this ...