NALIRIFOX as second-line chemotherapy for advanced extrapulmonary high-grade neuroendocrine neoplasms

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

This trial will try NALIRIFOX (liposomal irinotecan with fluorouracil and oxaliplatin) as a second-line treatment for adults with metastatic extrapulmonary high‑grade neuroendocrine neoplasms who progressed after first‑line therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07077551 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-center, single-arm Phase 2 trial testing NALIRIFOX in patients with extrapulmonary advanced high‑grade neuroendocrine neoplasms who have failed one prior systemic treatment. The study uses a two‑stage design, enrolling 12 patients in the first stage and continuing if prespecified activity is observed. The primary endpoint is 6‑month disease‑free survival and a key secondary endpoint is disease control rate measured by RECIST 1.1. Eligible participants are adults aged 18–75 with measurable metastatic G3 NET, NEC, or MiNEN (neuroendocrine component >30%) and ECOG performance status 0–1, and all visits are conducted at a single center in Hangzhou, Zhejiang.

Who should consider this trial

Good fit: Adults 18–75 with histologically confirmed metastatic extrapulmonary high‑grade neuroendocrine neoplasms (G3 NET, NEC, or MiNEN with >30% neuroendocrine component), measurable disease by RECIST 1.1, ECOG 0–1, life expectancy ≥3 months, and who have progressed after one prior systemic therapy are ideal candidates.

Not a fit: Patients older than 75, with ECOG >1, inadequate organ function, more than one prior systemic therapy, or with primary pulmonary neuroendocrine disease are unlikely to qualify or benefit from this protocol.

Why it matters

Potential benefit: If effective, NALIRIFOX could provide an additional disease‑control option and extend progression‑free time for patients needing second‑line therapy for extrapulmonary high‑grade NENs.

How similar studies have performed: Liposomal irinotecan‑containing regimens have shown clinical benefit in pancreatic cancer, but NALIRIFOX has not previously been tested in extrapulmonary high‑grade neuroendocrine neoplasms.

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

Where this trial is running

Hangzhou, Zhejiang

• Second Affiliated Hospital, School of Medicine, Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Conditions NENS