A Study of Mitoxantrone Hydrochloride Liposome Injection in the Treatment of Advanced Solid Tumor

A Multicenter, Randomized, Open-label, Phase Ib Study to Evaluate the Safety, Efficacy and Pharmacokinetic Characteristics of Mitoxantrone Hydrochloride Liposome Injection in Subjects With Advanced Solid Tumor

This is a multicenter, randomized, open-label, phase Ib study to evaluate the safety, efficacy and pharmacokinetic characteristics of Mitoxantrone Hydrochloride Liposome in subjects with advanced solid tumor.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Mitoxantrone Hydrochloride Liposome, intravenous injection (IV)

Detailed Description

This is a multicenter, randomized, open-label, phase Ib study to evaluate the safety, efficacy and pharmacokinetic characteristics of Mitoxantrone Hydrochloride Liposome in subjects with advanced solid tumor. 90 subjects will be recruited. The first 60 subjects will be randomly assigned into 2 groups, group A and group B. The 30 subjects in group A will receive the Mitoxantrone Hydrochloride Liposome 20 mg/m2 by an intravenous infusion (IV), every 28 days (q4w, 1 cycle). The 30 subjects in group B will receive Mitoxantrone Hydrochloride Liposome 20 mg/m2, IV, every 21 days (q3w, 1 cycle). After this, the last 30 subjects will be assigned into group B. All subjects will receive the treatment until disease progression, intolerable toxic reaction, death, or withdrawal by investigator or subject decision (a maximum of 8 cycles). Delays in drug administration is allowed from cycle 2, however, the delays should be no more than 3 weeks. Dose adjustments after cycle 2 is permitted, and the minimum dose is 12 mg/m2.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233099
      • The First Affiliated Hospital Of Bengbu Medical College
  • Guangdong
    • Guangzhou, Guangdong, China, 511399
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
  • Guizhou
    • Guiyang, Guizhou, China, 550000
      • The Affiliated Cancer Hospital of Guizhou Medical University
  • Hebei
    • Baoding, Hebei, China
      • Affiliated Hospital of Hebei University
  • Hubei
    • Wuhan, Hubei, China, 430060
      • Renmin Hospital of Wuhan University
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Shanghai Cancer Center
  • Sichuan
    • Yibin, Sichuan, China, 644199
      • Yibin Second People's Hospital
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University Cancer Institute & Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects fully understand and voluntarily participate in this study and sign informed consent;
2. Age ≥18, without gender limitation;
3. Histologically and/or cytologically confirmed diagnosis of unresectable local or metastasizing advanced solid tumor;
4. Fail to respond to standard therapy or lack of effective treatment, including no standard therapy, intolerance of standard therapy, etc.;
5. At least one measurable lesion according to RECIST v1.1;
6. ECOG performance status of 0 or 1;
7. AEs from the previous treatment have resolved to ≤ Grade 1 based on CTCAE (except for the toxicity without safety risk judged by the investigator, such as hair loss, hyperpigmentation);
8. Adequate organ function;
9. Subjects of childbearing potential must agree to use effective contraceptive measures. Female subjects must have a negative pregnancy test before enrollment;
10. Fully comply with the protocol.

Exclusion Criteria:

1. History of allergy to mitoxantrone hydrochloride or any excipients of the study drug;
2. Untreated or symptomatic central nervous system (CNS) metastases;
3. CTCAE Grade 3 or Grade 4 gastrointestinal hemorrhage within 12 weeks prior to the first dose administration;
4. History of allotransplantation;
5. Known hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or other active viral infection;
6. Serious infection or interstitial pneumonia within 1 week prior to the first dose administration;
7. Use of other anticancer treatment within 4 weeks prior to the first dose administration;
8. Enrolled in any other clinical trials within 4 weeks prior to the first dose administration;
9. Major surgery within 3 months prior to the first dose administration, or have a surgical schedule during the study period;
10. Thrombosis or thromboembolism within 6 months prior to screening;
11. History of, or known additional malignant tumor within 3 years, except for tumors have been cured and have not recurred, and carcinoma in situ;
12. Impaired cardiac function or serious cardiac disease;
13. Previous treatment with adriamycin or other anthracyclines, and the total cumulative dose of prior adriamycin or equivalent is >350 mg/m2;
14. Life expectancy<12 weeks;
15. Pregnant or lactating female;
16. Serious and/or uncontrolled systemic diseases;
17. Not suitable for this study as decided by the investigator due to other reasons.

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: Group A, Mitoxantrone Hydrochloride Liposome Injection, q4w; Subjects with advanced or metastatic solid tumor will receive Mitoxantrone Hydrochloride Liposome every 28 days (a cycle) for a maximum of 8 cycles. The starting dose of Mitoxantrone Hydrochloride Liposome is 20mg/m2.	Drug: Mitoxantrone Hydrochloride Liposome, intravenous injection (IV); Subjects will receive Mitoxantrone Hydrochloride Liposome 20 mg/ m2, IV, on day 1 of each cycle for a maximum of 8 cycles.
Experimental: Group B, Mitoxantrone Hydrochloride Liposome Injection, q3w; Subjects with advanced or metastatic solid tumor will receive Mitoxantrone Hydrochloride Liposome every 21 days (a cycle) for a maximum of 8 cycles. The starting dose of Mitoxantrone Hydrochloride Liposome is 20mg/m2.	Drug: Mitoxantrone Hydrochloride Liposome, intravenous injection (IV); Subjects will receive Mitoxantrone Hydrochloride Liposome 20 mg/ m2, IV, on day 1 of each cycle for a maximum of 8 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events (AEs)	The incidence and severity of AEs, abnormalities in physical exams, vital sign assessments, clinical laboratory assessments, ultrasonic cardiograms (UCGs) and electrocardiographs (ECGs).	from the first dose injection to 28 days after the last dose injection, assessed up to 36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate (ORR)	To investigate the preliminary antitumor efficacy	From the enrollment to the final documentation of response of the last subject (assessed up to 36 months)
duration of complete response (DCR)	To investigate the preliminary antitumor efficacy	From the enrollment to the final documentation of response of the last subject (assessed up to 36 months)
duration of response (DoR)	To investigate the preliminary antitumor efficacy	From the enrollment to CR,PR, PD, death, lost to follow-up, withdrawal, or study end, whichever occurred first, assessed up to 36 months
progression-free survival (PFS)	To investigate the preliminary antitumor efficacy	From the enrollment to CR,PR, PD, death, lost to follow-up, withdrawal, or study end, whichever occurred first, assessed up to 36 months
overall survival (OS)	To investigate the preliminary antitumor efficacy	From the enrollment to CR, PR, PD, death, lost to follow-up, withdrawal, or study end, whichever occurred first, assessed up to 36 months
maximum time (Tmax)	To investigate PK characteristics	Cycle 1 to cycle 4, approximately 16 weeks
maximum concentration (Cmax)	To investigate PK characteristics	Cycle 1 to cycle 4, approximately 16 weeks
area under the plasma concentration-time curve from time zero to the time of last observed concentration (AUC0-t)	To investigate PK characteristics	Cycle 1 to cycle 4, approximately 16 weeks
apparent terminal half-life (t1/2)	To investigate PK characteristics	Cycle 1 to cycle 4, approximately 16 weeks

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Investigators: Principal Investigator: Yehui Shi, MD, Tianjin Medical University Cancer Institute & Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2021
• Primary Completion (Anticipated): April 13, 2022
• Study Completion (Anticipated): April 13, 2024

Study Registration Dates

• First Submitted: December 14, 2020
• First Submitted That Met QC Criteria: January 19, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Mitoxantrone
• Other Study ID Numbers: HE071-CSP-017

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