Using Lenvatinib for treating advanced bone and soft tissue sarcomas

A Multicenter, Open, One-arm Phase II Study of Ranvastinib Mesylate Capsules in the Treatment of Advanced Bone and Soft Tissue Sarcoma After Chemotherapy Failure

This study is testing if a new medication called lenvatinib can help people with advanced bone and soft tissue sarcomas who haven't had success with other treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 10 Years to 70 Years
• Sex: All
• Sponsor: Henan Cancer Hospital (other gov)
• Drugs / interventions: apatinib, anlotinib, chemotherapy, immunotherapy, radiation, lenvatinib
• Locations: 1 site (Zhengzhou, Henan)
• Trial ID: NCT05617859 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of lenvatinib mesylate capsules in patients with metastatic or surgically unresectable bone and soft tissue sarcomas who have previously failed multi-target TKI therapy. A total of 60 patients aged 10-70 will be enrolled, and their response to treatment will be assessed based on established criteria. The study aims to provide insights into a potential new treatment option for this challenging condition.

Who should consider this trial

Good fit: Ideal candidates are patients aged 10-70 with metastatic or unresectable bone and soft tissue sarcomas who have previously failed multi-target TKI therapy.

Not a fit: Patients who have not received prior multi-target TKI therapy or those with resectable tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced bone and soft tissue sarcomas who have limited alternatives.

How similar studies have performed: While there have been studies on lenvatinib for other conditions, this specific application for advanced bone and soft tissue sarcomas is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Ages 10-70, both male and female.
2. The Eastern Collaborative Oncology Group (ECOG) physical status score was 0-1. Subjects with amputation can be relaxed up to 2 points.
3. The expected survival time was ≥3 months.
4. Subjects with bone and soft tissue sarcomas with distant metastases or locally advanced disease who were not considered suitable for surgical treatment by the investigator.
5. Patients who had been treated with apatinib or anlotinib in the past, and the efficacy was evaluated as CR\\PR\\SD\\PD, and had no response to other systemic therapy after drug resistance, or had reprogression after more than 3 months.
6. There were measurable lesions that met RECIST1.1 criteria.
7. All acute toxicities from previous antitumor therapy or surgery resolved to grade 0-1 (according to NCI-CTCAE, version 4.03) or to enrollment/exclusion criteria by day 1 of the first cycle (C1D1), except for toxicities such as hair loss that the investigator considered to pose no safety risk to the subject.
8. Adequate organ and bone marrow function is defined as follows:

   Blood routine (no blood transfusion, no G-CSF, no medication correction within 14 days before screening) :

   Neutrophil count (ANC)≥1,500/mm3(1.5×109/L); Platelet count (PLT)≥100,000/mm3(100×109/L); Hemoglobin (Hb)≥9g/dL(90g/L);

   Blood biochemical:

   Serum creatinine (Cr)≤1.5× upper limit of normal (ULN) or creatinine clearance (Cockroft-Gault formula)≥60ml/min; Total bilirubin (TBIL)≤1.5×ULN; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels ≤2.5×ULN, and subjects with liver metastases should ≤5×ULN;

   Blood coagulation function:

   International normalized ratio (INR)≤1.5, prothrombin time (PT) and activated partial thromboplastin time (APTT)≤1.5×ULN;
9. Urine routine: urinary protein \<2+; If urine protein ≥2+, 24-hour urine protein quantification must show protein ≤1g;
10. Thyroid function: Thyroid stimulating hormone (TSH)≤ULN; FT3(T3) and FT4(T4) levels should be examined if they are abnormal, and normal FT3(T3) and FT4(T4) levels can be selected.
11. Female subjects of reproductive age must have a negative serum pregnancy test within 7 days prior to medication and be willing to use a medically approved highly effective contraceptive (e.g., intrauterine device, birth control pill, or condom) during the study period and within 3 months after the last administration of the study drug; Male subjects with a female partner of reproductive age were required to undergo surgical sterilization or consent to use an effective method of contraception during the study period and for 3 months after the last study dose.
12. I have AGREED and signed the informed CONSENT, and I am willing AND ABLE TO comply with the planned visit, study treatment, laboratory tests and other trial procedures.

Exclusion Criteria:

1. C1D1 received the following treatments in the previous 4 weeks:

   Radiotherapy, surgery, chemotherapy, immunotherapy for tumors. Other investigational drugs. Get live attenuated vaccine.
2. Surgery and/or radiation therapy for bone and soft tissue sarcomas were planned during the study.
3. Previous use of immunosuppressive drugs within 14 days prior to C1D1, excluding nasal spray and inhaled corticosteroids or physiological doses of systemic steroid hormones (i.e., no more than 10mg/ day of prednisolone or an equivalent physiological dose of another corticosteroid).
4. Severe infection (such as the need for intravenous antibiotic, antifungal, or antiviral medication) within 4 weeks prior to C1D1, or unexplained fever \>38.5°C during the screening period/before the first dose.
5. Hypertension that is not well controlled with antihypertensive medication (systolic blood pressure \> 140 mmHg or diastolic blood pressure \>90mmHg).
6. Significant bleeding symptoms or clear bleeding tendency occurred within 3 months before C1D1, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ++ and above, vasculitis, etc. Or arteriovenous thrombotic events occurring within 6 months before C1D1, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; Long-term anticoagulant therapy with warfarin or heparin or long-term antiplatelet therapy (aspirin ≥300mg/ day or clopidogrel ≥75mg/ day) may be required.
7. Active heart disease in the 6 months prior to C1D1, including myocardial infarction and severe/unstable angina pectoris. Left ventricular ejection fraction \<50% on echocardiography, poorly controlled arrhythmias (including QTcF interval \>450ms in men and \>470ms in women).
8. C1D1 had been diagnosed with any other malignancy within 3 years prior to C1D1, except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix.
9. Known allergy to the study drug or any of its excipients.
10. Human immunodeficiency virus (HIV) infection, active hepatitis B (hepatitis B surface antigen positive and HBVDNA≥500IU/ml), and hepatitis C (hepatitis C antibody positive and HCV-RNA above the detection limit of the assay).
11. Concomitant diseases (e.g., poorly controlled hypertension, severe diabetes,neurological or mental disorders, etc.) or any other conditions that, in the judgment of the investigator, seriously endanger the safety of the subjects, may confounding the results of the study, or interfere with the completion of the study.

Where this trial is running

Zhengzhou, Henan

• Department of Bone and Soft Tissue ,Henan Cancer Hospital — Zhengzhou, Henan, China (RECRUITING)

Conditions: Effectiveness, Sexuality