A Prospective, Single-arm Clinical Study of Liposomal Mitoxantrone Combination Regimen in the Treatment of Relapsed and Refractory Solid Tumors in Children, Adolescents and Young Adults

The aim of this clinical study is to determine the efficacy and safety of the liposomal mitoxantrone combination regimen in treating relapsed and refractory solid tumors among children, adolescents, and young adults. The key questions it intends to address are:

Can the liposomal mitoxantrone combination regimen improve the objective response rate (ORR) compared to historical data? What are the adverse events associated with this combination regimen? Researchers will administer the liposomal mitoxantrone combination regimen (including capecitabine and anlotinib with specific dosing regimens) to the participants and closely monitor their conditions.

Participants will:

Receive the treatment regimen for 4 - 6 cycles, with each cycle lasting 21 days Undergo regular checkups and tests during the treatment period and follow-up period as per the protocol.

Have their tumor status, blood parameters, and other relevant indicators measured to evaluate the treatment effect and safety.

This is a prospective, single-arm, multicenter clinical study named "A Prospective, Single-arm, Multicenter Clinical Study of Liposomal Mitoxantrone Combination Regimen in the Treatment of Relapsed and Refractory Solid Tumors in Children, Adolescents and Young Adults". The study aims to assess the safety and effectiveness of the liposomal mitoxantrone combination regimen in treating relapsed and refractory solid tumors among children, adolescents, and young adults.

The research anticipates enrolling 49 patients meeting specific criteria. The inclusion criteria require patients to have a clear understanding of the study, sign the informed consent form voluntarily, fall within the age range of 6 - 24 years with an expected survival time exceeding 3 months, have histopathologically confirmed relapsed and refractory solid tumors of certain subtypes (such as bone and soft tissue tumors, neuroblastoma, etc.), possess measurable tumor lesions detectable by CT, enhanced CT, PET/CT or MRI, and meet specific Karnofsky and ECOG scores as well as requirements for bone marrow, liver, and kidney functions. Exclusion criteria cover those with hypersensitivity to study drugs, uncontrolled other malignancies, pregnant or lactating women, and those judged unsuitable by investigators.

The treatment regimen consists of capecitabine at a dose of 1000 mg/m² from day 1 to 14, twice daily, and anlotinib with the dose adjusted according to body weight for 14 days, with a 21-day cycle repeated 4 - 6 times. Patients achieving a partial response or better will undergo local treatment like surgery or radiotherapy.

The primary endpoint of the study is the objective response rate (ORR), while secondary endpoints include the proportion of patients eligible for local treatment after treatment, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events evaluated by NCI CTCAE v5.0. This study holds great significance for exploring new treatment options for relapsed and refractory solid tumors in the target population.

Eligibility Criteria:
Main inclusion Criteria:

1. The patient fully understands this study, voluntarily participates and signs the informed consent form (ICF).
2. Age: children (6 - 12 years old), adolescents (13 - 18 years old) and young adults (19 - 24 years old) (CAYA). The expected survival time is \> 3 months.
3. Diagnosed with relapsed and refractory solid tumors by histopathology, and it is one of the following subtypes: (1) bone and soft tissue tumors; (2) neuroblastoma; (3) other types of solid tumors that the investigator deems eligible for enrollment.
4. There must be measurable tumor lesions by CT, enhanced CT, PET/CT or MRI.
5. Karnofsky score \> 50; ECOG score ≤ 2.
6. Bone marrow function: neutrophil count \> 1.5 × 10⁹/L, platelet count \> 75 × 10⁹/L, hemoglobin ≥ 80 g/L.
7. Liver and kidney function: serum creatinine ≤ 1.5 times the upper limit of normal value; AST and ALT \< 2.5 times the upper limit of normal value (for patients with liver invasion \< 5 times the upper limit of normal value); total bilirubin \< 1.5 times the upper limit of normal value (for patients with liver invasion \< 3 times the upper limit of normal value).
8. No history of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, no history of clinically severe pericardial disease, or no electrocardiogram evidence of acute ischemic or active conduction system abnormality within 6 months before recruitment.

Main exclusion Criteria:

1. Patients with known hypersensitivity to any component of the study drugs.
2. Patients with other malignant tumors that are not under control (except for basal cell carcinoma of the skin, in-situ breast/cervical cancer, and other malignant tumors that have been effectively controlled without treatment in the past five years).
3. Pregnant, lactating women and women of childbearing age who are unwilling to take contraceptive measures.
4. Other situations judged by the investigator as not suitable for participating in this study.