What side effects are associated with this type of intervention?

Common treatments for Soft Tissue Sarcoma (STS), such as Doxorubicin and Lurbinectedin, have distinct side effect profiles. Doxorubicin is associated with cardiotoxicity, myelosuppression, mucositis, alopecia, nausea, and vomiting. Lurbinectedin can cause hematological toxicities. Other treatments like ifosfamide may lead to renal damage and neurotoxicity. Pegylated liposomal doxorubicin (PLD) can cause hand-foot syndrome and esophagitis. These treatments aim to maximize efficacy while managing side effects.

What prior FDA approvals exist?

Doxorubicin has been a cornerstone in the treatment of soft tissue sarcoma (STS) due to its mechanism as a DNA intercalator and topoisomerase II inhibitor. Other FDA-approved treatments for STS include Ifosfamide, which is often used in combination with Doxorubicin, and Trabectedin, a DNA minor groove binder similar to Lurbinectedin. Trabectedin has shown efficacy particularly in liposarcomas and leiomyosarcomas. Pazopanib, a multikinase angiogenesis inhibitor, is also approved for advanced STS, offering an alternative mechanism of action by targeting angiogenesis.

What other types of research exist?

Promising novel alternatives to Lurbinectedin with Doxorubicin for Soft Tissue Sarcoma patients include: 1) Trabectedin, which binds to the minor groove of DNA and affects transcription regulation, showing efficacy in leiomyosarcoma and liposarcoma. 2) Eribulin, a microtubule dynamics inhibitor, which has shown benefits in liposarcoma. 3) Pazopanib, a multi-targeted tyrosine kinase inhibitor, approved for advanced soft tissue sarcoma. These alternatives offer different mechanisms of action and have demonstrated clinical benefits in treating soft tissue sarcomas.

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Alkylating agent

Lurbinectedin + Doxorubicin for Leiomyosarcoma

Phase 1 & 2

Recruiting

Led By Gregory Cote, M.D. Ph.D

Research Sponsored by Massachusetts General Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

For participants with known chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

Age ≥ 18 years

Must not have

Participants receiving any medications or substances that are strong or moderate inhibitors or inducers of CYP3A, CYP2D6, or P-gp are ineligible

History of interstitial pneumonitis or pulmonary fibrosis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug, lurbinectedin, combined with an existing chemotherapy drug, doxorubicin, in patients with advanced leiomyosarcoma. The goal is to see if this combination is safe and more effective than doxorubicin alone. Both drugs work by damaging the DNA in cancer cells, leading to their death. Lurbinectedin is a synthetic marine-derived anticancer agent that has shown promise in treating certain types of cancer.

Who is the study for?

Adults with measurable soft tissue sarcoma, specifically leiomyosarcoma, who have no curative treatment options available. They must be over 18, not pregnant or breastfeeding, willing to use contraception, and have adequate organ function and bone marrow reserves. Prior cancer treatments are restricted.

What is being tested?

The trial is testing the combination of lurbinectedin and doxorubicin versus lurbinectedin alone for treating leiomyosarcoma. It has two parts: one for tolerability assessment and another randomized part to compare effectiveness.

What are the potential side effects?

Potential side effects include typical chemotherapy-related issues such as fatigue, nausea, hair loss (alopecia), heart problems due to doxorubicin's known cardiotoxicity, risk of infections from low white blood cell counts (neutropenia), liver function changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My hepatitis B virus load is undetectable with treatment.

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I am 18 years old or older.

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I can take care of myself but may not be able to do heavy physical work.

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My cancer is an advanced leiomyosarcoma with no cure through combined treatments.

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I have tissue samples from previous procedures available for testing.

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I had hepatitis C but have been treated and cured.

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My sarcoma is advanced or has spread, and there are no cure-focused treatments left for me.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not taking strong or moderate drugs that affect enzyme activity.

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I have had interstitial pneumonitis or pulmonary fibrosis.

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I received palliative radiation therapy within the last week.

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I have been diagnosed with cardiomyopathy.

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I have previously been treated with lurbinectedin.

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I have had radiation treatment to my pelvis with a dose over 45 Gy.

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I have had 2 or fewer chemotherapy treatments for the phase 1b study, and only 1 for the phase 2 study.

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I have previously been treated with anthracycline or trabectedin.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

PFS rate of lurbinectedin with doxorubicin compared to doxorubicin alone in participants with advanced LMS

The maximum tolerated dose (MTD) of lurbinectedin with doxorubicin in participants with advanced soft-tissue sarcoma

Secondary study objectives

Disease Control Rate Phase 1b

Disease Control Rate Phase 2

Number of Participants Treatment Related Adverse Events

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Lurbinectedin + Doxorubicin at RP2DExperimental Treatment2 Interventions

The randomized two arm phase 2 trial will begin following the determination of the RP2D for lurbinectedin and doxorubicin. * Participants will be randomized 1:1 to enroll to either Arm 1 or Arm 2 * Participants enrolled to Arm 1 will receive Lurbinectedin with Doxorubicin at the RP2D defined during the phase 1b portion of the trial.

Group II: Lurbinectedin + Doxorubicin Phase IExperimental Treatment2 Interventions

The phase 1b trial will follow a standard 3+3 design. Upon determination of the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of lurbinectedin plus doxorubicin. A treatment cycle will be defined as 21 consecutive days. Treatment will be administered on an outpatient basis * Lurbinectedin * Doxorubicin

Group III: Doxorubicin MonotherapyActive Control1 Intervention

The randomized two arm phase 2 trial will begin following the determination of the RP2D for lurbinectedin and doxorubicin. * Participants will be randomized 1:1 to enroll to either Arm 1 or Arm 2 * Participants enrolled to Arm 2 will receive Doxorubicin at the standard dose of 75 mg/m2

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Doxorubicin

2012

Completed Phase 3

~8030

Lurbinectedin

2022

Completed Phase 3

~780

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Lurbinectedin and Doxorubicin are common treatments for Soft Tissue Sarcoma (STS) that work by targeting the DNA of cancer cells. Lurbinectedin binds to the minor groove of DNA, inhibiting transcription and disrupting cancer cell replication. Doxorubicin intercalates into DNA, inhibiting the enzyme topoisomerase II, which is essential for DNA replication, and generates free radicals that cause DNA damage. These mechanisms are crucial for STS patients as they provide a targeted approach to killing cancer cells, potentially leading to more effective treatments and improved patient outcomes.

Chemotherapeutic treatment of xenograft Spirocerca lupi-associated sarcoma in a murine model.Current concepts in the management of retroperitoneal soft tissue sarcoma.