Clinical trial NCT04719065: A Study of Mitoxantrone Hydrochloride Liposome Injection in the Treatment of Advanced Solid Tumor
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-01-22
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: adverse events (AEs)
timeFrame: from the first dose injection to 28 days after the last dose injection, assessed up to 36 weeks
Secondary outcomes:
measure: overall response rate (ORR)
timeFrame: From the enrollment to the final documentation of response of the last subject (assessed up to 36 months)
measure: duration of response (DoR)
timeFrame: From the enrollment to CR,PR, PD, death, lost to follow-up, withdrawal, or study end, whichever occurred first, assessed up to 36 months
measure: duration of complete response (DCR)
timeFrame: From the enrollment to the final documentation of response of the last subject (assessed up to 36 months)
measure: progression-free survival (PFS)
timeFrame: From the enrollment to CR,PR, PD, death, lost to follow-up, withdrawal, or study end, whichever occurred first, assessed up to 36 months
measure: overall survival (OS)
timeFrame: From the enrollment to CR, PR, PD, death, lost to follow-up, withdrawal, or study end, whichever occurred first, assessed up to 36 months
measure: maximum time (Tmax)
timeFrame: Cycle 1 to cycle 4, approximately 16 weeks
measure: maximum concentration (Cmax)
timeFrame: Cycle 1 to cycle 4, approximately 16 weeks
measure: area under the plasma concentration-time curve from time zero to the time of last observed concentration (AUC0-t)
timeFrame: Cycle 1 to cycle 4, approximately 16 weeks
measure: apparent terminal half-life (t1/2)
timeFrame: Cycle 1 to cycle 4, approximately 16 weeks
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated Cancer Hospital of Guizhou Medical University
state: Guizhou
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Yibin
country: China
facility: Yibin Second People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Yehui Shi, MD
role: PRINCIPAL_INVESTIGATOR
References: