Study of Irinotecan Liposome Injection in Patients With Advanced Breast Cance

NCT04728035 | Completed Phase 1

• 1 other identifier: HE072-CSP-002
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (4)

• Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs)

  The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0.

  Up to six months after the last patient's first administration

• Dose limiting toxicity (DLT)

  DLT will be assessed according to NCICTCAE v5.0.

  Up to 28 days post-product injection

• Maximum Tolerated Dose (MTD, if available)

  MTD was defined as the previous dose level at which 2 out of 6 patients experienced a DLT.

  Up to 28 days post-product injection

• Recommended Phase 2 Dose (RP2D)

  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.

  Up to the end of the part 1

Secondary Outcomes (12)

• Objective Response Rate (ORR)

  Up to six months after the last patient's first administration

• Progression-Free Survival (PFS)

  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

• 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

Other Outcomes (1)

• UGT1A1 gene polymorphism and Topoisomerase I (Topo I) expression

  Up to six months after the last patient's first administration

Study Arms (2)

Dose escalation (part 1)

EXPERIMENTAL

Patients will receive irinotecan liposome injection (CSPC) at the initial starting dose until progression or unacceptable toxicity.

Drug: Irinotecan Liposome Injection

Dose expansion (part 2)

EXPERIMENTAL

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.

Drug: Irinotecan Liposome Injection

Interventions

Irinotecan Liposome Injection DRUG

Irinotecan Liposome Injection

Dose escalation (part 1); Dose expansion (part 2)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients 1.Female aged between 18 and 75 years.
• Histologically or cytologically confirmed breast cancer.
• At least one measurable lesion according to RECIST 1.1.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Life expectancy \>3 months.
• Patient should not receive blood transfusion or supportive care (eg. EPO, G-CSF or others) within 14 days before the initiate dose, and laboratory test should meet the following criteria: neutrophile count ≥1.5×10\^9/L platelet count ≥100×10\^9/L hemoglobin ≥90 g/L or ≥5.6 mmol/L serum creatinine ≤1.5×ULN and creatinine clearance rate ≥50 mL/min total bilirubin ≤1×ULN AST and ALT ≤2.5×ULN
• Patient with reproductive potential must agree to use adequate contraception from the signing of informed consent to at least 6 months after the trial completion and have a negative serum pregnancy test within 7 days before enrollment.
• Ability to understand and the willingness to sign a written informed consent.
• Additional criteria for dose escalation and cohort 1 in dose expansion
• Meet the molecular classification criteria for triple-negative breast cancer.

You may not qualify if:

• Patients who have received any investigational drug within 4 weeks of the first dose of the study drug.
• Patients who have undergone major organ surgery (excluding needle biopsy) or have significant trauma within 4 weeks prior to the first dose of the study drug, or have a schedule for major surgery during the trial.
• Patients who have concomitant use of strong CYP3A4 inhibitors or inducers within 2 weeks prior to receiving the first dose of irinotecan liposome injection, or CYP3A4 inhibitors or UGT1A1 inhibitors within 1 week prior to receiving the first dose of irinotecan liposome injection, or those who could not suspend the above drugs during the study.
• Patients who received systemic glucocorticoids (prednisone \>10 mg/day or equivalent dose of the similar drugs) or other immunosuppressive agents within 14 days before the first dose of the study drug. Except for local, ocular, intra-articular, intranasal, and inhaled glucocorticoids, short term use of glucocorticoids for preventive treatment (e.g., prevention of contrast allergy). Cohort 2 in dose expansion is not limited.
• Patients who have received prior topoisomerase I inhibitor treatment, including irinotecan or other investigational agents.
• Known hypersensitivity (CTCAE 5.0≥3) to any of the components of irinotecan liposome injection, or other liposomal products.
• Patients with central Nervous System (CNS) metastasis meet any of the following criteria: Cohort 2 in dose expansion is not limited.
• (1)Patients who have developed new or progressive brain metastasis following cranial radiation or surgery.
• (2)Patients with the symptomatic Central Nervous System (CNS) metastasis who have used cortisol, radiotherapy, dehydration drugs, etc. to control symptoms in the past two weeks.
• (3)Patients with carcinomatous meningitis.
• (4)Patients with brainstem (midbrain, pons, medulla oblongata) metastasis.
• (5)Patients have other evidence indicates that the patient's central nervous system metastasis or meningeal metastasis has not been controlled and is judged unsuitable for enrollment by the investigator.
• Patients who have pulmonary lymphatic dissemination and metastasis, leading to dyspnea at rest, may need to be combined with other treatments, such as oxygen inhalation, which is judged not suitable for enrollment by the investigator.
• Prior radiation therapy encompassing more than 30% of bone marrow.
• Patients have unresolved adverse reactions \> grade 1 (CTCAE 5.0) from previous anti-tumor treatment (except for the peripheral neuropathy \< grade 2, alopecia, and other toxicity judged no safety risk by investigators).

Sponsors & Collaborators

• CSPC Ouyi Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Cancer Hosptial of CAMS

Beijing, Beijing Municipality, China

Location

Related Publications (1)

• Fan Y, Zhang Q, Yan M, Qu X, Yin Y, Sun T, Yang J, Wang Y, Wang X, Niu Z, Wang X, Sun S, Zhao W, Liu Y, Niu M, Zhao X, Xu B. Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after >/= 2 prior lines of chemotherapy: a phase Ib study. Nat Commun. 2025 Jan 2;16(1):3. doi: 10.1038/s41467-024-55090-4.

  PMID: 39746964 DERIVED

MeSH Terms

Interventions

irinotecan sucrosofate

Study Design

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

Study Record Dates

• First Submitted: January 18, 2021
• First Posted: January 28, 2021
• Study Start: May 31, 2021
• Primary Completion: June 5, 2023
• Study Completion: June 5, 2024
• Last Updated: July 26, 2024

Record last verified: 2020-12

Locations

CN (1)