PrognostIc and Predictive Factors in Unresectable Locally Advanced NEC and MANEC

Neuroendocrine Carcinoma Clinical Trial

— NIRVANA  

Official title:

Retrospective and Prospective Observational Study on prognostIc and Predictive Factors in Patients With Extra-pulmonary, adVanced Neuroendocrine cArciNomas and Mixed Adeno-neuroendocrine Carcinomas (NIRVANA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06400654
• Other study ID #: IEO 1476
• Status: Recruiting
• Start date: July 5, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: European Institute of Oncology
• Contact: Francesca Spada, MD
• Phone: +390257489258
• Email: divisione.gastrointestinale[@]ieo.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Extra-pulmonary (EP) poorly differentiated neuroendocrine carcinomas (NECs) represent a rare and aggressive category of neoplasms. Mixed adeno-neuroendocrine carcinomas (MANEC) are a group of rare neoplasms composed by a neuroendocrine (NE) and a non-neuroendocrine (non-NE) component, each representing at least the 30% of the neoplasm.

Considering their rarity, low prevalence and poor prognosis a clear clinical, morphological and biomolecular characterization of these neoplasms has been prevented and a clinical approach universally shared is still lacking.

Description:

Extra-pulmonary (EP) poorly differentiated neuroendocrine carcinomas (NECs) represent a rare and aggressive category of neoplasms. They occur in almost 1 / 100.000 patients and the largest part is represented by gastro-entero-pancreatic (GEP) NECs (39%).

Moreover, mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) represent an even more rare entity, with a crude incidence of 0.1 / 100.000 / year, composed at least by 30% of a neuroendocrine (NE) and a non-neuroendocrine (non-NE) component based on the 2019 World Health Organization (WHO) classification. Focusing on the neuroendocrine counterpart, although the term MiNEN includes both well and poorly differentiated morphologies, the main part of them are represented by high grade neuroendocrine neoplasms categorized as MANECs in previous 2010 WHO classification that is a term still used in clinical practice is still lacking.

While for localized disease, surgery represents the cornerstone and virtually the unique curative approach, patients with metastatic disease are mostly managed with chemotherapy. Although any specific clinical practice guideline by Oncological and / or Neuroendocrine Societies has been yet developed worldwide, based on the clinical and morphological similarity with small and large cell lung NECs, cis / carbo-platinum based chemotherapy, is the most often chemotherapeutic regimen proposed in clinical practice both in NECs and MANECs from each site of origin. Other proposed options include regimens containing 5-fluorouracil/folinic-acid and irinotecan or oxaliplatin which are used also in the treatment of colo-rectal adenocarcinomas. Moreover, considering their rarity, low prevalence and poor prognosis a clear clinical, morphological and biomolecular characterization of these neoplasms has been prevented and a clinical approach universally shared is still lacking.

Therefore, a comprehensive clinical and biological characterization of these neoplasms represents an unmet medical need and a major challenge and could improve the awareness of clinicians in the management of EP-NECs and MANECs.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological diagnosis of unresectable locally advanced or metastatic NEC or MANEC confirmed by an expert-pathologist

• EP-primary site (included unknown primary site

• Age > 18 years

• Signed written informed consent

• Performance status =2

• Available tumor tissue (formalin-fixed paraffin-embedded, FFPE) (preferably within 6 months). If the tumor contained in FFPE tissue block cannot be provided in total, sections from this block should be provided that are freshly cut. Preferably, 25 slides should be provided (minimum of 15 slides). If tumor tissue is not available, patients should be willing to undergone to a new biopsy.

Exclusion Criteria:

• Diagnosis of well-differentiated NEN (G1, G2, G3)

• Collision tumors

• Cytological diagnosis of NEC or MANEC or not availability of tumor tissue for pathological analysis.

• Concurrent neoplastic disease (e.g. Advanced breast or prostatic cancer in hormonal treatment, hematologic diseases)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Neuroendocrine
• Neuroendocrine Carcinoma

Locations

Country	Name	City	State
Italy	European Institute of Oncology	Milan

Sponsors (1)

Lead Sponsor	Collaborator
European Institute of Oncology

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival clinical outcome	The primary clinical endpoint will be the overall survival.	3 years
Secondary	Progression free survival clinical outcome	The secondary clinical endpoint will be the progression free survival	3 years
Secondary	Mutational pattern	Mutational patterns such as BRAF, KRAS, NRAS, MSI, TP53, RB1 will be analyzed.	3 years
Secondary	Prognostic and predictive factors identification	The progression free survival and overall survival of patients with mutations will be evaluated.	3 years