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Advanced Soft-tissue SarcomaPhase 1/2NCT05099666

Lurbinectedin + Doxorubicin In Leiomyosarcoma

A Phase 1/2 study testing Lurbinectedin and Doxorubicin in people with Advanced Soft-tissue Sarcoma and Metastatic Soft-tissue Sarcoma, run by Massachusetts General Hospital at 6 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This research study involves the study drug lurbinectedin in combination with doxorubicin. This research has two parts. The first part is being done to determine the tolerability of lurbinectedin with doxorubicin in people with soft tissue sarcoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lurbinectedin and Doxorubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
6 sitesUnited States
Study dates
4 Feb 2022to Jul 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • For Enrollment to Phase 1b: Participants must have histologically confirmed advanced or metastatic soft-tissue sarcoma and no curative multimodality treatment options available.
  • For Enrollment to Phase 2: Participants must have histologically confirmed advanced or metastatic leiomyosarcoma (LMS) and no curative multimodality treatment options available.
  • Participants must have measurable disease per RECIST 1.1 criteria
  • Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of lurbinectedin in combination with doxorubicin in participants <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
  • ECOG performance status ≤ 2 (Karnofsky ≥ 60%,).
  • Participants must have adequate organ and marrow function as defined below:
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  • Absolute Neutrophil Count ≥ 1,500/mcL
  • Hemoglobin (Hgb) ≥ 8 g/dl (transfusion support permitted)
  • Platelet Count ≥ 100,000/mcL
  • Total Bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
  • AST (SGOT) / ALT(SGPT) ≤ 2.5 × institutional ULN, OR ≤ 5 × institutional ULN if elevation is a result of metastases
  • Creatinine ≤ 1.5 × institutional ULN, OR Creatinine Clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above 1.5 × institutional normal (calculated via the Cockcroft-Gault equation)
  • Creatine Phosphokinase (CPK)< 2.5 × institutional ULN on two different determinations performed one week (± 1 day) apart
  • For participants with known chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with known HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Left ventricular ejection fraction (LVEF) ≥ 50% on screening echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
  • The effects of lurbinectedin or doxorubicin on the developing human fetus are unknown. For this reason and because anti-cancer agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of study agent administration.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Participants must have archival tissue available for analysis in the form of a formalin-fixed paraffin embedded (FFPE) block or unstained slides. Participants without archival tissue available may be enrolled with approval of the Sponsor-Investigator. Note: confirmation of availability of archival tissue is the only requirement for eligibility, archival tissue does not need to be received by the study team or site prior to enrollment.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen as assessed by the treating investigator may be included with the approval of the Sponsor-Investigator.

Who cannot join

  • Participants who have received prior anthracycline or trabectedin (Yondelis, ET-743), including prior exposure to doxorubicin or liposomal doxorubicin.
  • Participants who have received more than 2 prior lines of cytotoxic chemotherapy for the phase 1b study and no more than 1 prior line of cytotoxic chemotherapy for the phase 2 study. There is no limit on the number of prior lines of non-cytotoxic chemotherapy (e.g., pazopanib, immunotherapy).
  • Prior exposure to lurbinectedin (PM01183).
  • Participants who have received prior radiation treatment of > 45 Gy to the pelvis.
  • Participants who have received or undergone prior chemotherapy within 14 days of cycle 1 day 1, therapeutic radiation therapy within 21 days of cycle 1 day 1 or major surgery within 21 days of cycle 1 day 1.
  • Participants who have received prior palliative radiation therapy within 7 days of cycle 1 day 1.
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  • Participants who have received prior antibody-based therapy (e.g., nivolumab) within 4 weeks or 3 half-lives (whichever is shorter) of cycle 1 day 1.
  • Participants who have received prior oral small molecule or tyrosine kinase inhibitor (TKI) therapy within 2 weeks or 3 half-lives (whichever is shorter) of cycle 1 day 1.
  • Participants who have not recovered to ≤ Grade 1 or baseline from adverse events attributed to any prior anti-cancer therapy, with the exceptions of alopecia, controlled endocrine toxicity (e.g., hypothyroidism), and cutaneous toxicity which will be permitted at Grade 2.
  • Participants who are receiving any other investigational agents.
  • Participants with known CNS disease involvement, with the exception of patients with brain metastases that have been previously treated and have remained stable on MRI ≥ 28 days prior to cycle 1 day 1 without use of steroids or anti-epileptic medications.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to lurbinectedin or doxorubicin.
  • Participants receiving any medications or substances that are strong or moderate inhibitors or inducers of CYP3A, CYP2D6, or P-gp are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant must be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
  • Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, chronic indwelling drains, or psychiatric illness/social situations that would limit compliance with study requirements.
  • History of interstitial pneumonitis or pulmonary fibrosis.
  • Known cardiomyopathy.
  • Pregnant women are excluded from this study because lurbinectedin and doxorubicin are anti-cancer agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lurbinectedin or doxorubicin, breastfeeding must be discontinued if the mother is treated with lurbinectedin or doxorubicin. A negative pregnancy test is required for women of childbearing potential prior to the first dose of study medication.
  • Immunocompromised patients, including patients who are known to be seropositive for human immunodeficiency virus (HIV) due to the increased risk of lethal infections when treated with marrow-suppressive therapy. HIV testing is not required as part of screening.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Mayo Jacksonville

    Jacksonville, Florida, 32224

  • Memorial Sloan Kettering

    New York, New York, 10065

  • Mayo Arizona

    Phoenix, Arizona, 85054

  • Mayo Rochester

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase 1b/2 Trial of Lurbinectedin Plus Doxorubicin in Leiomyosarcoma

This research study involves the study drug lurbinectedin in combination with doxorubicin.

This research has two parts. The first part is being done to determine the tolerability of lurbinectedin with doxorubicin in people with soft tissue sarcoma. The second part is a randomized study to determine which is more effective at treating leiomyosarcoma, lurbinectedin with doxorubicin or lurbinectedin alone.

Read the detailed description

This is an open label phase 1b/2 study exploring the safety and efficacy of lurbinectedin with doxorubicin.

  • 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, the randomized phase 2 trial in participants with advanced leiomyosarcoma (LMS) will commence. Participants will be randomized 1:1 for enrollment to one of two treatment arms:
  • Arm 1: Lurbinectedin with Doxorubicin
  • Arm 2: Doxorubicin Monotherapy

This is a Phase Ib/II clinical trial. A Phase Ib clinical trial tests the safety of an investigational drug combination and also tries to define the appropriate dose of the investigational drugs to use for further studies. "Investigational" means that the drugs are being studied.

The U.S. Food and Drug Administration (FDA) has not approved lurbinectedin for this specific disease but it has been approved for the treatment of small cell lung cancer.

The U.S. FDA has approved doxorubicin as a treatment option for soft-tissue sarcoma.

Lurbinectedin is a synthetically derived chemical that binds to DNA. The binding to DNA likely induces cell death. Doxorubicin is a cytotoxic chemotherapy drug that kills cancer cells by several mechanisms including binding to DNA.

Being tested
Lurbinectedin, Doxorubicin
Keywords
Advanced Soft-tissue Sarcoma, Metastatic Soft-tissue Sarcoma, Advanced Leiomyosarcoma, Leiomyosarcoma Metastatic
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LurbinectedinDrug

    Also called Zepzelca

    Dosage per protocol, escalation per protocol, IV over 60 minutes (± 5 minute infusion window), schedule per protocol

  • DoxorubicinDrug

    Also called Adriamycin

    Dosage per protocol, IV per institutional standards of practice and the FDA package insert, schedule per protocol

Study groups in NCT05099666
Study groupRoleWhat they receive
Lurbinectedin + Doxorubicin Phase IExperimentalThe 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
Receives: Drug: Lurbinectedin; Drug: Doxorubicin
Lurbinectedin + Doxorubicin at RP2DExperimentalThe 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.
Receives: Drug: Lurbinectedin; Drug: Doxorubicin
Doxorubicin MonotherapyActive comparatorThe 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
Receives: Drug: Doxorubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    The MTD will be defined as the dose where less than 1 in 3 patients experience a DLT. At least 6 patients must be treated at this dose level. DLTs will be defined as toxicities experienced by participants enrolled to the phase 1b portion of the trial that are considered at least possibly related to the treatment regimen, occur during the first cycle of treatment.

    Measured: 21 Days

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

    Progression-Free Survival (PFS) is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.

    Measured: Up to 5 years

Secondary outcomes (10)

  1. Disease Control Rate Phase 1b

    Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria

    Measured: 6 Months

  2. Disease Control Rate Phase 1b

    Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria

    Measured: 12 Months

  3. Progression Free Survival Phase 1b

    PFS is defined as the time from as the time from randomization (or registration) to the earlier of progression or death due to any cause, whichever occurs first

    Measured: Up to 5 years

  4. Overall Survival Phase 1b

    OS is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive.

    Measured: Up to 5 years

  5. Objective Response Phase 1b

    assessed by RECIST version 1.1 criteria

    Measured: Up to 5 years

  6. Disease Control Rate Phase 2

    Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria

    Measured: 6 Months

  7. Disease Control Rate Phase 2

    Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria

    Measured: 12 Months

  8. Overall Survival Rate Phase 2

    OS is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive.

    Measured: Up to 5 years

  9. Objective Response Rate Phase 2

    assessed by RECIST version 1.1 criteria

    Measured: Up to 5 years

  10. Number of Participants Treatment Related Adverse Events

    NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2021
  2. Study start4 Feb 2022
  3. Primary completionDec 2026 (estimated)
  4. Study completionJul 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
62 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05099666
Sponsor's protocol ID
21-437
Status last verified
Aug 2026
First submitted
1 Oct 2021
Last updated
27 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lurbinectedin and Doxorubicin in people with Advanced Soft-tissue Sarcoma and Metastatic Soft-tissue Sarcoma, run by Massachusetts General Hospital at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The maximum tolerated dose (MTD) of lurbinectedin with doxorubicin in participants with advanced soft-tissue sarcoma (time frame: 21 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05099666.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.

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