NALIRIFOX as Second-Line Chemotherapy in Extrapulmonary High-grade Neuroendocrine Neoplasms: a Prospective, Single-center, Single-arm Trial

Launched by SECOND AFFILIATED HOSPITAL, SCHOOL OF MEDICINE, ZHEJIANG UNIVERSITY · Jul 20, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new chemotherapy treatment called NALIRIFOX for people with advanced high-grade neuroendocrine tumors (NENs) outside the lungs. These tumors can be aggressive and often don’t respond well to first treatments. This study focuses on patients whose cancer has not improved after their initial therapy. Researchers want to see if NALIRIFOX can help control the disease and keep it from getting worse for at least six months.

To take part, patients need to be adults up to 75 years old with a confirmed diagnosis of high-grade neuroendocrine tumors or related types, and their cancer must have spread. They should have already tried one systemic treatment without success and be in generally good health with measurable tumors that haven’t recently been treated with radiation. Participants will receive the study drug and be closely monitored to check how well the cancer responds and to watch for side effects. The study will first include 12 patients, and if enough of them benefit, it will expand to enroll more. This trial is important because it explores a new option for patients with few effective treatments available, potentially leading to larger studies and new standards of care.

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Eligibility criteria

• Inclusion Criteria:
• • 1. Provide written Informed Consent Form to voluntarily enroll in this study.
• • 2. Men or women aged 18-75.
• • 3. Histologically or cytologically confirmed metastatic neuroendocrine carcinoma, neuroendocrine tumour G3 or mixed neuroendocrine-non-neuroendocrine tumour (neuroendocrine component \>30%)
• • 4. Patients who have failed one previous systemic treatment.
• • 5. ECOG PS score of 0 or 1.
• • 6. Life expectancy is at least 3 months.
• • 7. The investigator assessed the presence of measurable lesions at baseline by imaging (according to RECIST 1.1), and measurable lesions should not have received local treatment such as radiotherapy (lesions located within the area of previous radiotherapy may also be selected as target lesions if progression is confirmed to have occurred).
• • 8. Function of vital organs in accordance with the following requirements (no blood components, cell growth factor corrective therapy with any medication is permitted within 14 days prior to the first use of the study drug); ① Absolute neutrophil count (ANC) ≥1.5×109/L
• • ② Platelets ≥ 100 x 109/L;
• • ③ Haemoglobin ≥ 8g/dL;
• • ④ Total bilirubin ≤ 1.5 × ULN; ALT, AST ≤ 2.5 × ULN, and if liver metastases are present, ALT, AST ≤ 5 × ULN;
• • ⑤ Serum creatinine ≤ 1.5 × ULN or creatinine clearance \> 60 mL/min (Cockcroft-Gault);
• • 9. Female subjects of childbearing potential are required to have a negative serum pregnancy test within 72 hours prior to initiation of trial drug administration and to use effective contraception (e.g., IUD, birth control pills, or condoms) during the trial period and for at least 3 months after the last dose; male subjects whose partner is a female of childbearing potential are required to use effective contraception during the trial period and for at least 3 months after the last dose. For male subjects whose partners are women of childbearing potential
• Exclusion Criteria:
• • 1. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects who have been previously treated for brain metastases may participate in treatment provided they have stable brain metastases and have not been treated for brain metastases with steroids for at least 28 days prior to study entry. This exception does not include carcinomatous meningitis, as patients with carcinomatous meningitis are excluded regardless of clinical stability;
• • 2. Major surgery, open biopsy or severe trauma 28 days prior to first dose;
• • 3. Prior history of allergy to fluorouracil or irinotecan;
• • 4. Have high blood pressure that is not well controlled by antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg)
• • 5. Subjects with uncontrolled cardiovascular clinical conditions or disease, including but not limited to: e.g., (1) NYHA class II or higher heart failure (2) unstable angina (3) myocardial infarction within 1 year (4) clinically significant supraventricular or ventricular arrhythmia not controlled without or with clinical intervention
• • 6. Have experienced clinically significant bleeding symptoms or have a definite tendency to bleed within 3 months prior to the first dose, e.g. peptic haemorrhage, haemorrhagic gastric ulcer or have vasculitis;
• • 7. Arterial/venous thrombotic events such as cerebrovascular accidents (including temporary ischaemic attack, cerebral haemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism occurring within 6 months prior to the first dose of the drug, with superficial vein thrombosis being eligible for enrolment as determined by the investigator; and
• • 8. There is another malignancy that is progressing or requires active treatment, with the exception of non-melanoma skin cancers and cervical cancer in situ for which potential treatment has already been undertaken;
• • 9. Women who are pregnant or breastfeeding;
• • 10. In the judgement of the investigator, the subject has other factors that may cause him/her to be forced to terminate the study midway, such as other serious illnesses (including psychiatric illnesses) that require comorbid treatment, severely abnormal laboratory test values, family or social factors that may affect the subject's safety or the collection of experimental data