LeiomyosarcomaPhase 1/2LEADERNCT03526679
Lenvatinib and Eribulin in Advanced Soft Tissue Sarcoma
A Phase 1/2 study testing Eribulin and Lenvatinib in people with Leiomyosarcoma and Liposarcoma, run by National Taiwan University Hospital at 2 sites in Taiwan.
Trial summary
This study is designed to test the safety and efficacy of the combination of lenvatinib, a drug that can inhibit the growth of supplying vessels around the tumors, and eribulin, a chemotherapy drug that targets the cancer cell during mitosis, in inoperable or metastatic adipocytic sarcoma and leiomyosarcoma. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Leiomyosarcoma, Liposarcoma, Soft Tissue Sarcoma Adult
- What is being tested?
- Eribulin and Lenvatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesTaiwan
- Study dates
- 12 Jul 2018to 30 Oct 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A histological confirmed adipocytic sarcoma (dedifferentiated, myxoid, or pleomorphic) or leiomyosarcoma that is either inoperable locally advanced or metastatic
- Advanced adipocytic sarcoma and leiomyosarcoma who have received no more than 2 lines of systemic chemotherapy in the advanced setting (not including adjuvant chemotherapy).
- At least one measurable tumor according to RECIST 1.1. If the measurable lesion has previously received radiotherapy, the tumor must be a progressive lesion after radiotherapy.
- ECOG PS 0 or 1 or Karnofsky performance status (KPS) ≥ 70
- Patients must have adequate organ function and marrow reserve measured within 14 days prior to randomization as defined below:
- Hemoglobin ≥ 9.0 g/dL;
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- Absolute neutrophil count ≥ 1,500 /µL;
- Platelets ≥ 75,000/µL;
- Total bilirubin ≤ 1.5 x upper normal limit;
- aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤ 2.5 x upper normal limit; for patients with liver metastases AST(SGOT)/ALT(SGPT) ≤ 5 x upper normal limit is allowed;
- Serum creatinine ≤ 1.5mg/dL or creatinine clearance ≥ 50ml/min;
- activated partial thromboplastin time (aPTT) < 1.5 x upper normal limit (unless on therapeutic anti-coagulation);
- Proteinuria ≤ 1+ with urine dipstick, if > 1+, 24-hour urine protein must be ≤ 1 g
- Age 20 or older.
- Patient's life expectancy is more than 3 months
- All women of childbearing potential must have a negative pregnancy test obtained within 72 hours before starting therapy.
- Patients with reproductive potential must use effective contraception (hormone or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after the completion of therapy.
- Patient needs to have adequate wash-out period from previous systemic treatment(s):
- 2 weeks for any other oral anti-cancer targeted agents (2) 3 weeks for any other cytotoxic chemotherapy (except for mitomycin-C, which will require 6 weeks) (3) 3 weeks for monoclonal antibodies, including immune checkpoint inhibitors
Who cannot join
- Patients who had received lenvatinib or eribulin treatment
- Patients who had leptomeningeal metastasis, either diagnosed by brain imaging study or confirmed by cerebrospinal fluid cytology examination (patients with brain metastasis that are under control is eligible).
- Patients with clinical signs or symptoms of gastrointestinal obstruction and who require parenteral hydration and/or nutrition because of obstruction.
- Patients with uncontrollable hypertension (defined as systolic blood pressure over 140mmHg and/or diastolic pressure over 90mmHg despite anti-hypertensive medications)
- Patients with the following cardiac disease
- Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms).
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- Significant cardiovascular impairment: history of (a) congestive heart failure greater than New York Heart Association (NYHA) Class II; (b) unstable angina; (c) myocardial infarction; (d) stroke; or (e) cardiac arrhythmia associated with hemodynamic instability within 6 months of the first dose of study drugs.
- Bleeding subjects at risk for severe hemorrhage.
- Arterial thromboembolic event within the past 6 months, including transient ischemic attack, cerebrovascular accident, unstable angina, or myocardial infarction.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment.
- History of allergic reaction to compounds of similar chemical composition to the study drugs
- Pregnancy or lactation.
Trial locations and contacts
2 sites in 1 country.
Taiwan2 sites
Taipei Veterans General Hospital
Taipei, Taiwan
National Taiwan University Hospital
Taipei, 100
About this study
Official title: A Single-arm Phase Ib/II Study of the Combination of Lenvatinib and Eribulin in Advanced Adipocytic Sarcoma and Leiomyosarcoma (LEADER Study)
This study is designed to test the safety and efficacy of the combination of lenvatinib, a drug that can inhibit the growth of supplying vessels around the tumors, and eribulin, a chemotherapy drug that targets the cancer cell during mitosis, in inoperable or metastatic adipocytic sarcoma and leiomyosarcoma.
Read the detailed description
Recently, the US Food and Drug Administration (FDA) granted approval to eribulin for the treatment of adipocytic sarcoma who have received a prior anthracycline-containing regimen based on a Phase III study results of improved overall survival (OS) as compared with the standard treatment dacarbazine. In the leiomyosarcoma cohort of the study, although eribulin did not demonstrate a significant benefit over dacarbazine, still about 5.1% of leiomyosarcoma patients treated with eribulin had a partial response, suggesting that eribulin may have activity against leiomyosarcoma. However, the overall response rate (ORR) and progression-free survival (PFS) remained unsatisfactory in the two most common soft tissue sarcoma (STS) subtypes-adipocytic sarcoma and leiomyosarcoma, prompting new therapeutic options of STS patients.
Anti-angiogenic therapies had shown promising results in soft tissue sarcoma (ST). Pazopanib, an anti-angiogenic multi-kinase inhibitor, has shown clinical benefit with a longer median PFS of 4.6 months versus placebo in STS patients refractory to at least one line of systemic chemotherapy. Another anti-angiogenic targeted therapy, regorafenib, showed significant improvement in PFS as compared with placebo in various STS. In a phase I study of lenvatinib for solid tumors in Japan, 4 out of 6 leiomyosarcoma patients has tumor decreased more than 10%. Moreover, other tyrosine receptor targets of lenvatinib, such as fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor (PDGFR), may also plays a role in treating STS. In high-grade STS patients, about 30% of patients had FGFR1 amplification or overexpression. FGFR1-overexpression STS cell lines are sensitive to FGFR inhibitors such as BGJ398 and AZD45475. Furthermore, a monoclonal antibody of PDGFR alpha, olaratumab, was recently approved by the FDA in combination with doxorubicin for advanced STS based on a median 10-month OS benefit compared to doxorubicin only in a randomized phase II trial.
It has been demonstrated in various cancer types that an increased quantity of tumor infiltrating lymphocyte (TILs) is associated with increased response to chemotherapy or improved prognosis. One of the factors that had been shown to impede the migration and trafficking of TILs into tumor is vascular endothelial growth factor (VEGF). In renal cell carcinoma, treatment with bevacizumab, an anti-VEGF antibody, or in combination with atezolizumab, increased the recognition of tumor antigen, increased expression of major histocompatibility complex (MHC) class I receptor on tumor cells, and the amount of TIL migration into the tumor stroma9. Many of the STS were detected with scarce TILs in the tumor microenvironment, thus it would be interesting to see if anti-angiogenic tyrosine kinase inhibitors could adjust the tumor microenvironment toward a more chemotherapy-friendly milieu.
Thus, we would like to propose a clinical trial to understand the anti-tumor activity of the combination of lenvatinib and eribulin in advanced STS patients.
- Being tested
- Eribulin, Lenvatinib
- Keywords
- soft tissue sarcoma, phase Ib/II, advanced cancer
- Medical subject headings
- Leiomyosarcoma, Liposarcoma, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EribulinDrug
Also called Halaven
lenvatinib 14mg po daily; eribulin 1.1mg/m2 D1, D8, every 21 days
LenvatinibDrug
Also called Lenvima
lenvatinib 14mg po daily; eribulin 1.1mg/m2 D1, D8, every 21 days
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | The combination of lenvatinib and eribulin Receives: Drug: Eribulin; Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Objective Response Rate (ORR) Based on RECIST 1.1
We will measure the radiographic changes of the tumor based on a prespecified criteria called RECIST (Response evaluation criteria in solid tumors). A tumor decreased in the sum of longest diameters of measurable tumors of more than 30% is considered responsive; a growth of tumor more than 20% in the sum of the longest diameter is considered disease progression; and shrinkage or growth between these intervals is considered stable disease (SD).
Measured: 24 weeks
Secondary outcomes (4)
The Proportion of Patients Who Are Progression-free and Alive at 24 Weeks
We will measure how many patients (proportion) of the participants that the tumor has progressed in the first 24 weeks of treatment
Measured: 24 weeks
Overall Survival (OS) Rate at 12-months
The definition of 12-months OS rate is the percentage of patients who had NOT has an event before or at 12 months. An event is defined as follows: Death due to any cause.
Measured: 12 months
Overall Survival (OS) Rate at 6 Months
The definition of 6 months OS rate is the percentage of patients who had NOT has an event before or at 6 months. An event is defined as follows: Death due to any cause.
Measured: 6 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Toxicities will be assessed according to CTCAE 4.03. The number of all grade toxicities will be recorded
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2018
- Study start12 Jul 2018
- Primary completion30 Jun 2021
- Study completion30 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeiomyosarcomaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Taipei Veterans General Hospital, Taiwan
- Responsible party
- Sponsor
- Investigators
- Wei-Wu Chen, MD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03526679
- Sponsor's protocol ID
- 201801101MIPB
- Acronym
- LEADER
- Status last verified
- Oct 2025
- First submitted
- 19 Apr 2018
- Last updated
- 5 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chen TW, Hsu CL, Hong RL, Lee JC, Chang K, Yu CW, Chen SC, Guo JC, Chen ML, Hsu MC, Kung TF, Cheng AL, Yen CC. A Single-Arm Phase Ib/II Study of Lenvatinib plus Eribulin in Advanced Liposarcoma and Leiomyosarcoma. Clin Cancer Res. 2022 Dec 1;28(23):5058-5065. doi: 10.1158/1078-0432.CCR-22-2092.
PubMed 36129471
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm Phase Ib/II Study of the Combination of Lenvatinib and Eribulin in Advanced Adipocytic Sarcoma and Leiomyosarcoma (LEADER Study)
- ClinicalTrials.gov ID
- NCT03526679
- Acronym / sponsor ID
- LEADER / 201801101MIPB
- Keywords
- soft tissue sarcoma, phase Ib/II, advanced cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- Taipei Veterans General Hospital, Taiwan
- Study start
- 12 Jul 2018 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Oct 2025 (actual)
- First posted
- 16 May 2018 (actual)
- Results
- Posted 25 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to test the safety and efficacy of the combination of lenvatinib, a drug that can inhibit the growth of supplying vessels around the tumors, and eribulin, a chemotherapy drug that targets the cancer cell during mitosis, in inoperable or metastatic adipocytic sarcoma and leiomyosarcoma.
Detailed description
Recently, the US Food and Drug Administration (FDA) granted approval to eribulin for the treatment of adipocytic sarcoma who have received a prior anthracycline-containing regimen based on a Phase III study results of improved overall survival (OS) as compared with the standard treatment dacarbazine. In the leiomyosarcoma cohort of the study, although eribulin did not demonstrate a significant benefit over dacarbazine, still about 5.1% of leiomyosarcoma patients treated with eribulin had a partial response, suggesting that eribulin may have activity against leiomyosarcoma. However, the overall response rate (ORR) and progression-free survival (PFS) remained unsatisfactory in the two most common soft tissue sarcoma (STS) subtypes-adipocytic sarcoma and leiomyosarcoma, prompting new therapeutic options of STS patients.
Anti-angiogenic therapies had shown promising results in soft tissue sarcoma (ST). Pazopanib, an anti-angiogenic multi-kinase inhibitor, has shown clinical benefit with a longer median PFS of 4.6 months versus placebo in STS patients refractory to at least one line of systemic chemotherapy. Another anti-angiogenic targeted therapy, regorafenib, showed significant improvement in PFS as compared with placebo in various STS. In a phase I study of lenvatinib for solid tumors in Japan, 4 out of 6 leiomyosarcoma patients has tumor decreased more than 10%. Moreover, other tyrosine receptor targets of lenvatinib, such as fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor (PDGFR), may also plays a role in treating STS. In high-grade STS patients, about 30% of patients had FGFR1 amplification or overexpression. FGFR1-overexpression STS cell lines are sensitive to FGFR inhibitors such as BGJ398 and AZD45475. Furthermore, a monoclonal antibody of PDGFR alpha, olaratumab, was recently approved by the FDA in combination with doxorubicin for advanced STS based on a median 10-month OS benefit compared to doxorubicin only in a randomized phase II trial.
It has been demonstrated in various cancer types that an increased quantity of tumor infiltrating lymphocyte (TILs) is associated with increased response to chemotherapy or improved prognosis. One of the factors that had been shown to impede the migration and trafficking of TILs into tumor is vascular endothelial growth factor (VEGF). In renal cell carcinoma, treatment with bevacizumab, an anti-VEGF antibody, or in combination with atezolizumab, increased the recognition of tumor antigen, increased expression of major histocompatibility complex (MHC) class I receptor on tumor cells, and the amount of TIL migration into the tumor stroma9. Many of the STS were detected with scarce TILs in the tumor microenvironment, thus it would be interesting to see if anti-angiogenic tyrosine kinase inhibitors could adjust the tumor microenvironment toward a more chemotherapy-friendly milieu.
Thus, we would like to propose a clinical trial to understand the anti-tumor activity of the combination of lenvatinib and eribulin in advanced STS patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental arm | Experimental | Drug: Eribulin, Drug: LenvatinibThe combination of lenvatinib and eribulin |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- A histological confirmed adipocytic sarcoma (dedifferentiated, myxoid, or pleomorphic) or leiomyosarcoma that is either inoperable locally advanced or metastatic
- Advanced adipocytic sarcoma and leiomyosarcoma who have received no more than 2 lines of systemic chemotherapy in the advanced setting (not including adjuvant chemotherapy).
- At least one measurable tumor according to RECIST 1.1. If the measurable lesion has previously received radiotherapy, the tumor must be a progressive lesion after radiotherapy.
- ECOG PS 0 or 1 or Karnofsky performance status (KPS) ≥ 70
- Patients must have adequate organ function and marrow reserve measured within 14 days prior to randomization as defined below:
Key exclusion criteria (12 listed)
- Patients who had received lenvatinib or eribulin treatment
- Patients who had leptomeningeal metastasis, either diagnosed by brain imaging study or confirmed by cerebrospinal fluid cytology examination (patients with brain metastasis that are under control is eligible).
- Patients with clinical signs or symptoms of gastrointestinal obstruction and who require parenteral hydration and/or nutrition because of obstruction.
- Patients with uncontrollable hypertension (defined as systolic blood pressure over 140mmHg and/or diastolic pressure over 90mmHg despite anti-hypertensive medications)
- Patients with the following cardiac disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EribulinAlso: Halavenlenvatinib 14mg po daily; eribulin 1.1mg/m2 D1, D8, every 21 days | Drug | Experimental arm |
| LenvatinibAlso: Lenvimalenvatinib 14mg po daily; eribulin 1.1mg/m2 D1, D8, every 21 days | Drug | Experimental arm |
Primary outcome
The Objective Response Rate (ORR) Based on RECIST 1.1
Time frame: 24 weeks
We will measure the radiographic changes of the tumor based on a prespecified criteria called RECIST (Response evaluation criteria in solid tumors). A tumor decreased in the sum of longest diameters of measurable tumors of more than 30% is considered responsive; a growth of tumor more than 20% in the sum of the longest diameter is considered disease progression; and shrinkage or growth between these intervals is considered stable disease (SD).
4 secondary outcomes
The Proportion of Patients Who Are Progression-free and Alive at 24 Weeks
Time frame: 24 weeks
Overall Survival (OS) Rate at 12-months
Time frame: 12 months
Overall Survival (OS) Rate at 6 Months
Time frame: 6 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36129471Chen TW, Hsu CL, Hong RL, Lee JC, Chang K, Yu CW, Chen SC, Guo JC, Chen ML, Hsu MC, Kung TF, Cheng AL, Yen CC. A Single-Arm Phase Ib/II Study of Lenvatinib plus Eribulin in Advanced Liposarcoma and Leiomyosarcoma. Clin Cancer Res. 2022 Dec 1;28(23):5058-5065. doi: 10.1158/1078-0432.CCR-22-2092.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wei-Wu Chen, MD principal investigator
National Taiwan University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Eribulin and Lenvatinib in people with Leiomyosarcoma and Liposarcoma, run by National Taiwan University Hospital at 2 sites in Taiwan.
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 19 inclusion and 12 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: finished, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Taiwan. 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?
Yes. Results are posted in the registry (first posted 25 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Objective Response Rate (ORR) Based on RECIST 1.1 (time frame: 24 weeks). 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 NCT03526679, which also lists 1 linked publication.
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 5 Dec 2025.