A Study of Mitoxantrone Hydrochloride Liposome Injection Combination Therapy in Chinese Patients With Advanced Solid Tumors

NCT05344742 | Unknown Phase 1

• 1 other identifier: HE071-CSP-027
• Study Type: interventional
• Target: 116
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the tolerability, safety, pharmacokinetics (PK) and efficacy of mitoxantrone hydrochloride liposome injection combination therapy in Chinese patients with advanced solid tumors.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Dose Limit toxicity (DLT)

  Dose limiting toxicity

  Up to 21 days after the first dose

• Treatment-emergent adverse events (TEAEs):

  TEAE is defined as an event that occurs during treatment and does not exist before treatment or worsens compared to before treatment as assessed by CTCAE v5.0.

  From the initiation of the first dose to 28 days after the last dose

Secondary Outcomes (12)

• Pharmacokinetic profile: Cmax

  Pre-dose and multiple timepoints up to Cycle 4th (each cycle is 21 days)

• Objective response rate (ORR)

  Throughout the study completion, up to 3 years

• Disease control rate (DCR)

  Throughout the study completion, up to 3 years

• Duration of response (DoR)

  Throughout the study completion, up to 3 years

• Progression-free survival (PFS)

  Throughout the study completion, up to 3 years

Study Arms (2)

Mitoxantrone Hydrochloride Liposome Injection and Capecitabine

EXPERIMENTAL

Dose-escalation phase: Patients will receive mitoxantrone hydrochloride liposome injection and capecitabine followed by a 3-week DLT observation period. The initial dose of mitoxantrone hydrochloride liposome injection will be set as 18 mg/m\^2, and then the dose will be sequentially escalated to 24 mg/m\^2 and 30 mg/m\^2. The frequency of administration will be once every three weeks. The fixed dose of capecitabine will be set as 1000 mg/m\^2, twice daily, from day 1 to day 14. Every 3 weeks will be set as a treatment cycle, and the administration of drugs is planned for 6 cycles. Dose-expansion phase: one dose cohort will be selected for dose-expansion to further evaluate the safety and efficacy of mitoxantrone hydrochloride liposome injection and capecitabine, and the administration of drugs is planned for 6 cycles.

Drug: Mitoxantrone Hydrochloride Liposome injection; Drug: Capecitabine

Mitoxantrone Hydrochloride Liposome Injection and albumin-paclitaxel

EXPERIMENTAL

Dose-escalation phase: Patients will receive mitoxantrone hydrochloride liposome injection and albumin-paclitaxel followed by a 3-week DLT observation period. The initial dose of mitoxantrone hydrochloride liposome injection will be set as 18 mg/m\^2, and then the dose is sequentially escalated to 24 mg/m\^2 and 30 mg/m\^2. The frequency of administration will be once every three weeks. The fixed dose of albumin-paclitaxel will be set as 260 mg/m\^2, once every three weeks. Every 3 weeks will be set as a treatment cycle, and the administration of drugs is planned for 6 cycles. Dose-expansion phase: one dose cohort will be selected for dose-expansion to further evaluate the safety and efficacy of mitoxantrone hydrochloride liposome injection and albumin-paclitaxel, and the administration of drugs is planned for 6 cycles.

Drug: Mitoxantrone Hydrochloride Liposome injection; Drug: Albumin-paclitaxel

Interventions

Mitoxantrone Hydrochloride Liposome injection DRUG

Mitoxantrone hydrochloride liposome injection will be administered intravenously once every 3 weeks (a cycle)

Mitoxantrone Hydrochloride Liposome Injection and Capecitabine; Mitoxantrone Hydrochloride Liposome Injection and albumin-paclitaxel

Capecitabine DRUG

The fixed dose of oral capecitabine will be administered 1000mg/m\^2, twice daily, from day 1 to day 14.

Mitoxantrone Hydrochloride Liposome Injection and Capecitabine

Albumin-paclitaxel DRUG

The fixed dose of albumin-paclitaxel will be set as 260 mg/m\^2, once every three weeks.

Mitoxantrone Hydrochloride Liposome Injection and albumin-paclitaxel

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients fully understand and voluntarily participate in this study and sign informed consent;
• Aged 18-65 years, male or female;
• Patients with advanced solid tumors confirmed by histopathology or cytologically and who have failed standard therapy;
• At least one measurable lesion according to RECIST v1.1 at baseline;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
• Adverse events（AEs） from the previous treatment have resolved to ≤ Grade 1 based on CTCAE (except for alopecia, hyperpigmentation and the toxicity without safety risk judged by the investigator);
• Adequate organ function defined as:
• Absolute neutrophil count (ANC) ≥1.5\*10\^9/L (No Granulocyte Colony Stimulating Factor treatment within 2 weeks prior to the laboratory test);
• Hemoglobin ≥ 90 g/L (No red blood cell transfusion within 2 weeks prior to the laboratory test);
• Platelet count ≥ 100\*10\^9/L (No platelet transfusion within 2 weeks prior to the laboratory test);
• Creatinine ≤1.5 upper limit of normal (ULN);
• Total bilirubin ≤1.5 ULN;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3ULN, ≤ 5ULN for patients with liver metastases;
• Coagulation: prothrombin time (PT) and International Normalization Ratio (INR) ≤1.5ULN；
• Female patients must have a urine or blood human chorionic gonadotropin（HCG） negative test before enrolment (except for menopause and hysterectomy); Patients and their partners must agree to use effective contraceptives measures during the study until 6 months after the end of the last dose.

You may not qualify if:

• History of severe allergy to mitoxantrone hydrochloride or liposomal drugs; allergy to capecitabine or any excipients of its components; previous serious and unexpected reaction to fluoropyrimidine or known allergy to fluorouracil; known complete deficiency of dihydropyrimidine dehydrogenase (DPD) activity; allergy to paclitaxel or human albumin;
• Cerebral or meningeal metastases;
• Life expectancy \< 3 months;
• Patients with chronic hepatitis B (HBsAg or HBcAb positive with HBV DNA ≥ 2000 IU/mL), chronic hepatitis C (HCV antibody positive with HCV RNA above the lower limit of detection of the study center), or human immunodeficiency virus (HIV) antibody positive;
• Active bacterial, fungal or viral infections that require intravenous infusion treatment within 1 week prior to the first dose;
• Any anticancer treatment within 4 weeks prior to the first dose (e.g., radiotherapy, targeted therapy, immunotherapy, endocrine therapy, etc.); Traditional Chinese medicine or proprietary Chinese medicine with an approved oncology indication within 2 weeks prior to the first dose;
• Enrolled in any other clinical trials within 4 weeks prior to the first dose;
• Patients have undergone major surgery within 3 months prior to the first dose, or have a surgical schedule during the study period;
• Serious thrombosis or thromboembolism as judged by the investigator within 6 months prior to screening;
• History of additional malignant tumor within 3 years, except for locally curable cancer that has been cured, such as basal or squamous cell skin cancer or in situ prostate, cervical or breast cancer;
• Patients with the following cardiac function defects:
• Long QTc syndrome or QTc interval \> 480 ms;
• Complete left bundle branch block, II-III degree atrioventricular block (except after pacemaker implantation);
• Severe, uncontrolled arrhythmias requiring pharmacological treatment;
• History of chronic congestive heart failure, NYHA grade III\~IV;

Sponsors & Collaborators

• CSPC ZhongQi Pharmaceutical Technology Co., Ltd.: lead

MeSH Terms

Interventions

Capecitabine

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Yanping Liu

CONTACT

+86-010-63930582; liuyanping@mail.ecspc.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2022
• First Posted: April 25, 2022
• Study Start: April 1, 2022
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2025
• Last Updated: April 25, 2022

Record last verified: 2022-04