Study of Everolimus as Maintenance Therapy for Metastatic NEC With Pulmonary or Gastroenteropancreatic Origin

NCT02687958 | Unknown Phase 2 DMC

• 1 other identifier: GOIRC 02/2014
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

Cisplatin and Etoposide is the standard of care in NEC originating from the gastro-intestinal tract and lung, based on retrospective studies. Nevertheless the prognosis of this group of patients is still poor with median survival of less than 20 months. Everolimus is an mammilian target of rapamycin (mTOR) inhibitor that has been demonstrated to be active in patients with well and moderately differentiated primitive neuroectodermal tumor (pNET). Recently, the Investigators demonstrated that the mammilian target of rapamycin (mTOR) pathway is overexpressed in NEC. Based on the activity of Everolimus in the treatment of patients with well and moderately differentiated p-NET and on the evidence that even poorly differentiated forms express the pathway of m-TOR is conceivable that Everolimus could be active even in NEC.

Conditions

Neuroendocrine Carcinoma

Keywords

GEP/ NEC

Outcome Measures

Primary Outcomes (1)

• PFS

  progression free survival (PFS)

  24 months

Secondary Outcomes (2)

• OS

  24 months

• ctDNA

  24 months

Study Arms (2)

A Everolimus 10mg (every cycle) until PD

EXPERIMENTAL

Patients with stable disease, partial response or complete response after 4- 6 cycles of induction chemotherapy with Cisplatin or Carboplatin plus Etoposide or alternative first line chemotherapy according with local practice will receive maintenance therapy with Everolimus 10mg every cycle (28days) until PD or unacceptable toxicity.

Drug: Everolimus

B Observational

NO INTERVENTION

Patients in this arm will meet observation criteria

Interventions

Everolimus DRUG

Maintenance therapy

Also known as: Afinitor

A Everolimus 10mg (every cycle) until PD

Eligibility Criteria

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

You may qualify if:

• Histological / cytological diagnosis of GEP Neuroendocrine Carcinoma (NEC) with Ki67\< 55% (WHO 2010)
• Histological/cytological diagnosis of large-cells neuroendocrine carcinoma of the lung with Ki67 \<55%;
• Stable disease, partial response or complete response (Recist 1.1) after 6 cycles of first line chemotherapy with Cisplatin plus Etoposide or alternative first line chemotherapy according with local practice
• non functional NEC
• locally advanced inoperable or metastatic disease
• measurable or evaluable disease according to RECIST criteria (version 1.1)
• Age\> 18;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
• Adequate bone marrow function (Hb\> 9.0 g / dL, absolute neutrophil count\> 1.5 x 109 / L, platelets\> 100 x 109 / L), renal function (serum creatinine \<2 mg / dL x upper limit of normal (ULN) or creatinine clearance, Cockroft formula, ≥ 30 ml / min), hepatic function (serum bilirubin \<1.5 x ULN, serum transaminases \<2.5 x ULN in the absence of liver metastases or \<5x ULN in the presence of liver metastases);
• Negative pregnancy test or breastfeeding women during childbearing age;
• Written informed consent;
• Approval of the Ethics Committee that will be required.

You may not qualify if:

• clinically significant cardiovascular disorders in the 6 months prior to randomization (congestive heart failure, myocardial infarction, unstable angina, severe uncontrolled cardiac arrhythmia, arterial thrombosis, cerebrovascular accidents, pulmonary thromboembolism);
• Functional Neuroendocrine Carcinoma NEC
• Neuroendocrine carcinoma with ki 67 \> 55%
• ongoing uncontrolled infection;
• Concomitant intake of:
• Drugs incompatible with concomitant everolimus;
• Any other drug in clinical trials;
• History of other malignancy except carcinoma in situ of the cervix or basal / squamous cell carcinoma of the skin adequately treated;
• Presence of brain metastases;
• Any other serious or uncontrolled concurrent disease conditions that the safe administration of medications

Sponsors & Collaborators

• Gruppo Oncologico Italiano di Ricerca Clinica: lead
• Novartis: collaborator

Study Sites (5)

S.C. Oncologia - Policlinico

Modena, Emilia-Romagna, 41124, Italy

Location

U.O. Oncologia Medica 1 - AOU Pisana

Pisa, Tuscany, 56126, Italy

Location

Azienda Ospedaliera "Spedali Civili di Brescia"

Brescia, 25123, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

MeSH Terms

Conditions

Carcinoma, Neuroendocrine

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Francesco Di Costanzo, MD

  AOU Careggi

  PRINCIPAL INVESTIGATOR

• Lorenzo Antonuzzo, MD

  AOU Careggi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2016
• First Posted: February 22, 2016
• Study Start: May 1, 2015
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2023
• Last Updated: May 30, 2023

Record last verified: 2023-05

Locations

IT (5)