Clinical Trial of VIM With VIT in Children With Relapsed and Refractory Soft Tissue Sarcoma.

Phase II Randomized Controlled Clinical Trial of Mitoxantrone Hydrochloride Liposome Combined With Irinotecan and Vincristine (VIM) With VIT in Children With Relapsed and Refractory Soft Tissue Sarcoma.

Explore the efficacy and safety of mitoxantrone liposome combined with irinotecan and vincristine (VIM) in the treatment of relapsed/refractory soft tissue sarcoma in children.

Study Overview

• Status: Recruiting
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Mitoxantrone Hydrochloride Liposome+Irinotecan+Vincristine; Drug: Temozolomide+Irinotecan+Vincristine

Detailed Description

Children with relapsed/refractory soft tissue sarcoma who meet the inclusion criteria are randomly divided into VIM group and VIT group (irinotecan, vincristine, temozolomide) at 1:1. The efficacy and safety of the two groups are compared.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yizhuo Zhang, PhD; Phone Number: 020-87342460; Email: zhangyzh@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Yi-Zhuo Zhang, MD; Phone Number: 87342460; Email: zhangyzh@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 2 years ≤age≤21 years, no gender limitation.
• The Karnofsky (≥16 years old) or Lansky (< 16 years old) physical status score is at least 70.
• The expected survival time is not less than 12 weeks.
• Heart function: a) Cardiac COLOR ultrasound detection LVEF≥ 50%; b) ECG suggests no myocardial ischemia; c) No history of arrhythmia requiring drug intervention before enrollment.
• Pathological results for patients of soft tissue sarcoma.
• Patients with rhabdomyosarcoma are limited to first -, second -, and third-line treatment, and patients with other pathological subtypes are limited to progression, recurrence, or refractory after first-line treatment, with refractory defined as failure to achieve complete or partial response to the most recent treatment.
• Measurable lesions (according to RECIST 1.1 standards, measurable lesions have not received radiotherapy, freezing and other local treatments).
• The patient must fully recover from the acute toxic effects of all previous anticancer chemotherapy.
• Good blood and organ function.
• During study participation, patients are able to adhere to outpatient treatment, laboratory monitoring, and necessary clinical visits.
• The parent/guardian of the child or adolescent subject is capable of understanding, agreeing to, and signing the study Informed consent (ICF) and the applicable child consent form prior to initiating any program-related procedures; Subject is capable of expressing consent with parental/guardian consent (if applicable).

Exclusion Criteria:

• Once received mitoxantrone or mitoxantrone liposomes.
• Patients who had received previous VIT (irinotecan + temozolomide + vincristine) chemotherapy.
• Previous treatment with adriamycin or other anthracyclines with a total cumulative dose of adriamycin > 360 mg/m^2; Or patients with cardiac disease caused by previous anthracyclines.
• Receiving or not being able to discontinue P450 enzyme-induced anticonvulsant drugs (e.g., phenytoin, carbamazepine, etc.) within 4 weeks or 5 half-life periods prior to enrollment.
• Previous or concurrent clinical significance of active cardiovascular diseases.
• Severe chronic skin diseases in the past.
• Previous allergic asthma or severe allergic disease.
• Uncontrolled hypertension and diabetes.
• Have a history of other tumors, except cured cervical cancer or basal cell carcinoma of the skin.
• Active hepatitis B or hepatitis C infection.
• HIV or syphilis infected patients.
• Patients who have previously received organ transplants.
• Uncontrolled active systemic bacterial, viral, or fungal infection.
• Contraindications to high-dose hormone use, such as uncontrolled hyperglycemia, gastric ulcers, or psychiatric disorders.
• Severe neurological or psychiatric history, including epilepsy or autism.
• Pregnant, lactating women and patients of childbearing age who are unwilling to use contraception.
• Other circumstances deemed inappropriate by the investigator to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VIM; Mitoxantrone Hydrochloride Liposome combined with Irinotecan and Vincristine.	Drug: Mitoxantrone Hydrochloride Liposome+Irinotecan+Vincristine; Mitoxantrone hydrochloride liposome will be administered by an intravenous infusion , 4 cycles.
Active Comparator: VIT; Temozolomide combined with Irinotecan and Vincristine.	Drug: Temozolomide+Irinotecan+Vincristine; Q3W, 4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Objective response rate (ORR) after 2 cycles of chemotherapy with VIM or VIT regimen, including complete response (CR) and partial response (PR)	Up to 2 cycles of chemotherapy (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Objective response rate (ORR) after 4 cycles of chemotherapy with VIM or VIT regimen, including complete response (CR) and partial response (PR)	Up to 4 cycles of chemotherapy (each cycle is 21 days)
Disease control rate (DCR)	Refers to the percentage of patients with confirmed complete response, partial response, and disease stability in patients with evaluable efficacy	Up to 4 cycles of chemotherapy (each cycle is 21 days)
Progression-free survival (PFS)	Means from the date of enrollment to the date of first disease progression or death from any cause, whichever comes first. If the subject has no disease progression during the trial period, PFS is defined as the last date until the subject's last confirmed progression-free survival.	From date of radomization unit the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 moths.
Overall survival (OS)	Overall survival (OS) was defined from the date of enrollment to the date of death from any cause.	From date of radomization unit the date of first documented date of death from any cause, assessed up to 24 moths

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating tumor DNA (ctDNA) .	ctDNA was dynamically monitored and the correlation between ctDNA and efficacy was evaluated.	Assessed up to 24 moths.

Collaborators and Investigators

• Sponsor: Yizhuo Zhang

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 4, 2024
• First Submitted That Met QC Criteria: July 22, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): July 23, 2024
• Last Update Submitted That Met QC Criteria: July 22, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Temozolomide; Irinotecan; Vincristine; Mitoxantrone
• Other Study ID Numbers: CSPC-DED-STS-K01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No