A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Irinotecan Liposome Injection in Patients With Advanced Breast Cancer
Overview
- Phase
- Phase 1
- Intervention
- Irinotecan Liposome Injection
- Conditions
- Advanced Breast Cancer
- Sponsor
- CSPC Ouyi Pharmaceutical Co., Ltd.
- Enrollment
- 119
- Locations
- 1
- Primary Endpoint
- Dose limiting toxicity (DLT)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This study is an open-label, single-arm, phase I study of irinotecan liposome injection in patients with advanced breast cancer. The purpose of this study is to evaluate the safety, efficacy and pharmacokinetics of irinotecan liposome injection in patients with advanced breast cancer.
Detailed Description
This is an open-label, single-arm, phase I study with a dose-escalation phase (part 1) and a dose-expansion phase (part 2). In part 1, patients will receive irinotecan liposome injection (CSPC) at the initial starting dose until progression or unacceptable toxicity. Dosages will be escalated by certain increments in subsequent cohorts. Once the appropriate dose has been established in part 1, patients will be enrolled into two expansion cohorts in part 2.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All patients 1.Female aged between 18 and 75 years.
- •2.Histologically or cytologically confirmed breast cancer.
- •3.At least one measurable lesion according to RECIST 1.
- •4.The time interval between the end of the last anti-tumor treatment and the first administration of irinotecan liposome injection is restricted as follows:
- •(1) More than 6 weeks for nitrosoureas (such as carmustine, lomustine, etc.) or mitomycin C.
- •(2) More than 3 weeks for cytotoxic chemotherapeutics, immunotherapy such as PD-1/PD-L1 and biotherapy.
- •(3) More than 2 weeks (five half-lives, whichever is longer) for oral fluorouracil, oral small molecule targeted drugs, and endocrine therapy.
- •(4) More than 2 weeks for Radiotherapy. (5) More than 2 Weeks for traditional Chinese medicine with anti-tumor indications.
- •5.Eastern Cooperative Oncology Group (ECOG) performance status 0 to
- •6.Life expectancy \>3 months.
Exclusion Criteria
- Not provided
Arms & Interventions
Dose escalation (part 1)
Patients will receive irinotecan liposome injection (CSPC) at the initial starting dose until progression or unacceptable toxicity.
Intervention: Irinotecan Liposome Injection
Dose expansion (part 2)
Once the appropriate dose has been established in Part 1, patients will be enrolled into two expansion cohorts according to the sub-type of breast cancer.
Intervention: Irinotecan Liposome Injection
Outcomes
Primary Outcomes
Dose limiting toxicity (DLT)
Time Frame: Up to 28 days post-product injection
DLT will be assessed according to NCICTCAE v5.0.
Recommended Phase 2 Dose (RP2D)
Time Frame: Up to the end of the part 1
RP2D was defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability data collected during the dose escalation portion of the study.
Maximum Tolerated Dose (MTD, if available)
Time Frame: Up to 28 days post-product injection
MTD was defined as the previous dose level at which 2 out of 6 patients experienced a DLT.
Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs)
Time Frame: Up to six months after the last patient's first administration
The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0.
Secondary Outcomes
- Progression-Free Survival (PFS)(Up to six months after the last patient's first administration)
- Duration of Response (DOR)(Up to six months after the last patient's first administration)
- Overall survival (OS)(Up to six months after the last patient's first administration)
- Objective Response Rate (ORR)(Up to six months after the last patient's first administration)
- The time to maximum concentration (Tmax)(-30minutes~168 hours)
- CNS clinical benefit rate (CNS CBR)(Up to six months after the last patient's first administration)
- Disease Control Rate (DCR)(Up to six months after the last patient's first administration)
- CNS objective response rate (CNS ORR)(Up to six months after the last patient's first administration)
- The Apparent volume of distribution (Vd)(-30 minutes~168 hours)
- The Area under the concentration-time curve from time zero to infinity (AUCinf)(-30minutes~168hours)
- The Maximum observed plasma concentration (Cmax)(-30 minutes~168 hours)
- The terminal elimination half-life (T1/2)(-30 minutes~168 hours)