Irinotecan Liposomes for the Treatment of Neuroendocrine Carcinoma

NCT ID: NCT06485739

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-01
• Study Completion Date: 2028-09-01

Brief Summary

This study is a real-world clinical study. It is expected to include 20 patients with first-line and second-line gastrointestinal pancreatic neuroendocrine carcinoma who will be treated with irinotecan liposomes combined with cisplatin or carboplatin regimen. The research unit is the First Affiliated Hospital of Xi'an Jiaotong University. The study includes a screening period (within 28 days), a treatment period (planned for 6 cycles), and a follow-up period (safety follow-up and PFS follow-up). The subjects signed an informed consent form and underwent baseline examination during the screening period. Patients who met the inclusion and exclusion criteria entered the treatment period. All subjects completed the relevant examinations specified in the protocol during the treatment process to observe safety, tolerance, and efficacy. The same subject only received one dosing plan during the study period. After the treatment period ends, enter the follow-up period.

Detailed Description

Neuroendocrine tumors (NENs) are a type of tumor originating from stem cells and possessing neuroendocrine markers that can produce bioactive amines and/or peptide hormones. Due to their heterogeneity and inertness, they have been defined as "carcinoids". Due to differences in origin, pathological grading, and treatment methods, NEN has different clinical manifestations and prognosis. Although NEN still meets the definition of rare disease, its incidence rate has increased significantly worldwide in the past decades. In the United States, the incidence rate of NEN in 2012 was 6.98/100000, about seven times the incidence rate reported in 1973 (1.09/100000). Among them, gastrointestinal and pancreatic neuroendocrine tumors (GEP NENs) are the most common type of NEN, accounting for 67.5% of all NEN cases. They mainly occur in the digestive tract or pancreas and can produce amine substances and peptide hormones such as glucagon, insulin, gastrin, or adrenocorticotropic hormone (ACTH).

We analyzed the data of ordinary irinotecan in first-line and second-line treatment of GEP-NEC and found that a prospective Phase II clinical study included 66 patients with advanced GEP-NEC. The results showed that the efficacy of the first line treatment using EP and IP regimens was equivalent, with an effective rate of over 40%. However, the efficacy of the second-line FOLFOX and FOLFIRI regimens is not ideal. Studies by HENTIC et al. have shown that the response rate of GEP-NEC to the FOLFIRI regimen is 31%, but the PFS is only 4 months; DU et al. also found that the median PFS of the FOLFIRI regimen was only 6.5 months in 11 patients with gastrointestinal NEC. The current research results on the FOLFOX regimen are similar. If there are studies showing that FOLFOX is used as a second-line regimen to treat 12 patients with advanced GEP-NEC, the median PFS is 4.5 months. HEETFELD et al. observed the efficacy of the FOLFIRI/FOLFOX regimen in GEP-NEC patients on the second or third line, and the results also showed a median PFS of 3.0 months and 2.5 months for the second and third line groups, respectively. Overall, the second-line treatment regimens recommended by the NCCN guidelines have not shown ideal efficacy and PFS in GEP-NEC.

Based on the literature review above and the birth of independently developed irinotecan liposomes by Shiyao, we plan to conduct a real-world study on the combination of irinotecan liposomes and platinum based treatment of gastrointestinal neuroendocrine carcinoma. The aim is to explore the efficacy and safety of a combination of irinotecan liposomes and platinum based chemotherapy regimen in first-line and second-line patients with gastrointestinal neuroendocrine carcinoma, providing better clinical evidence of efficacy and safety.

Conditions

Neuroendocrine Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Irinotecan liposome combined administration group

The combination of irinotecan liposomes and cisplatin or carboplatin regimen is recommended for treatment, with a recommended dose of 70mg/m2 for irinotecan liposomes. For UGT1A1 \* 28 homozygous patients, the initial dose of irinotecan liposomes is adjusted to 50mg/m2. If the patient tolerates during the first treatment cycle, the dose can be adjusted to 70mg/m2 for subsequent treatment cycles; Every 4 weeks is a treatment cycle, with 6 cycles of treatment. If the researcher determines that the patient can continue to benefit from 6 cycles of treatment, the treatment will continue until 8 cycles;

Group Type: EXPERIMENTAL

Irinotecan liposomes combined with cisplatin/carboplatin

Intervention Type: DRUG

Irinotecan liposomes 70mg/m2，use on the first day of each cycle The dosage of cisplatin and carboplatin is determined by the researchers

Interventions

Irinotecan liposomes combined with cisplatin/carboplatin

Irinotecan liposomes 70mg/m2，use on the first day of each cycle The dosage of cisplatin and carboplatin is determined by the researchers

Intervention Type: DRUG

Other Intervention Names

Irinotecan liposomes group

Eligibility Criteria

Inclusion Criteria

• The patient fully understands this study, voluntarily participates and signs an informed consent form (ICF);
• Age: ≥ 18 years old;
• Expected survival time ≥ 3 months;
• Patients with high-grade gastrointestinal pancreatic neuroendocrine tumors (NET G3) and neuroendocrine cancers (NECs) confirmed by histopathology;
• Have not undergone or undergone a systematic anti-tumor treatment in the past;
• According to RECIST 1.1 standard, patients must have at least one measurable diameter target lesion (tumor lesion CT scan length ≥ 10mm, lymph node lesion CT scan short diameter ≥ 15mm, scan layer thickness 5mm);
• ECOG score 0-2 points;
• Absolute neutrophil count (ANC) ≥ 1.5 x 10 ^ 9/L, platelet count ≥ 100 x 10 ^ 9/L, and hemoglobin count ≥ 90 g/L;
• Liver and kidney function: serum creatinine ≤ 1.5 times the upper limit of normal value; AST and ALT ≤ 2.5 times the upper limit of normal values (≤ 5 times the upper limit of normal values for patients with liver invasion); Total bilirubin ≤ 1.5 times the upper limit of normal value (≤ 3 times the upper limit of normal value for patients with liver invasion);
• Women of childbearing age must undergo a pregnancy test (serum) within 7 days before enrollment, and the result is negative. They are willing to use appropriate methods of contraception during the trial period and 8 weeks after the last administration of the investigational drug;

Exclusion Criteria

• Patients with neuroendocrine tumors G1 and G2;
• Has hypersensitivity to any investigational drug or its components;
• Diagnosed as intestinal obstruction through imaging;
• Uncontrollable systemic diseases (such as infection during the promotion period, uncontrollable hypertension, diabetes, etc.);
• Active infection of hepatitis B and hepatitis C (hepatitis B B virus surface antigen is positive and hepatitis B B virus DNA exceeds 1x103 copies/mL; hepatitis C virus RNA exceeds 1x103 copies/mL);
• Human Immunodeficiency Virus (HIV) infection (HIV antibody positive);
• Has previously or currently suffered from other malignant tumors (except for effectively controlled non melanoma skin basal cell carcinoma, breast/cervical carcinoma in situ, and other malignant tumors that have not been treated and have been effectively controlled within the past five years);
• Pregnant and lactating women, as well as patients of childbearing age who are unwilling to take contraceptive measures;
• Patients with other malignant tumors that require treatment;
• The researchers determined that patients who are not suitable to participate in this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role: lead

Responsible Party

Li EnXiao

Medical professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

EnXiao Li, PhD

Role: STUDY_DIRECTOR

First Affiliated Hospital of Xian Jiaotong University

Central Contacts

EnXiao Li, PhD

Role: CONTACT

doclienxiao@sina.com

18991232168

XuYuan Dong, PhD

Role: CONTACT

15332304217

Other Identifiers

2024-101

Identifier Type: -

Identifier Source: org_study_id