Lurbinectedin + Doxorubicin In Leiomyosarcoma
A Phase 1b/2 Trial of Lurbinectedin Plus Doxorubicin in Leiomyosarcoma
1 other identifier
interventional
62
1 country
6
Brief 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. The second part is a randomized study to determine which is more effective at treating leiomyosarcoma, lurbinectedin with doxorubicin or lurbinectedin alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2022
Longer than P75 for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 1, 2021
CompletedFirst Posted
Study publicly available on registry
October 29, 2021
CompletedStudy Start
First participant enrolled
February 4, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2027
April 13, 2026
April 1, 2026
4.4 years
October 1, 2021
April 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
21 Days
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.
Up to 5 years
Secondary Outcomes (10)
Disease Control Rate Phase 1b
6 Months
Disease Control Rate Phase 1b
12 Months
Progression Free Survival Phase 1b
Up to 5 years
Overall Survival Phase 1b
Up to 5 years
Objective Response Phase 1b
Up to 5 years
- +5 more secondary outcomes
Study Arms (3)
Lurbinectedin + Doxorubicin Phase I
EXPERIMENTALThe 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
Lurbinectedin + Doxorubicin at RP2D
EXPERIMENTALThe 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.
Doxorubicin Monotherapy
ACTIVE 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
Interventions
Dosage per protocol, escalation per protocol, IV over 60 minutes (± 5 minute infusion window), schedule per protocol
Dosage per protocol, IV per institutional standards of practice and the FDA package insert, schedule per protocol
Eligibility Criteria
You may qualify if:
- 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:
- 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.
- +5 more criteria
You may not qualify if:
- 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.
- 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.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Massachusetts General Hospitallead
- Jazz Pharmaceuticalscollaborator
Study Sites (6)
Mayo Arizona
Phoenix, Arizona, 85054, United States
Mayo Jacksonville
Jacksonville, Florida, 32224, United States
Massachusetts General Hospital
Boston, Massachusetts, 02115, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Mayo Rochester
Rochester, Minnesota, 55905, United States
Memorial Sloan Kettering
New York, New York, 10065, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Gregory Cote, M.D. Ph.D
Massachusetts General Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
October 1, 2021
First Posted
October 29, 2021
Study Start
February 4, 2022
Primary Completion (Estimated)
July 1, 2026
Study Completion (Estimated)
July 1, 2027
Last Updated
April 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- Contact the Partners Innovations team at http://www.partners.org/innovation
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.