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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase II Randomized Multicenter Study of Everolimus as Maintenance Therapy for Metastatic Neuroendocrine Carcinoma With Pulmonary or Gastroenteropancreatic Origin

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.


Detailed Summary:

A platinum based chemotherapy (Cisplatin or Carboplatin) plus Etoposide is the standard of care in NEC originating from the gastro-intestinal tract and lung, based on retrospective studies. In these clinical studies and in clinical practice the median number of cycle administered is six due to dose depending toxicity of platinum and to the concept of maximum response.

The expression of mTOR pathways was evaluated in gastroenteropancreatic - Neuroendocrine tumor (GEP-NEC).

The Investigator found that 6/9 (67%) of poorly differentiated GEP-NEC evaluated expressed p mTOR. Interestingly this expression was not observed in small cell carcinoma (10).

Recently, was demonstrated that the mTOR pathway is overexpressed in NEC (11). 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. In particular we want to test the hypothesis that a maintenance therapy (or an early second line) with Everolimus 10 mg/daily in non progressive patients after first line chemotherapy could improve outcome prolonging progression free survival (PFS).

The NORDIC NEC study recently published retrospectively analyzed 305 patients with metastatic GI NEC (or unknown primary predominantly with GI metastases).

In this large retrospective study patients with Ki-67 < 55% are less responsive to platinum based chemotherapy but have a longer survival than patients with Ki-67 > 55%; then Ki-67 < 55% is a positive prognostic factor and a negative predictive factor to platinum based chemotherapy (7).

Sponsor: Gruppo Oncologico Italiano di Ricerca Clinica

Current Primary Outcome: PFS [ Time Frame: 24 months ]

progression free survival (PFS)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • OS [ Time Frame: 24 months ]
    Overall survival (OS)
  • ctDNA [ Time Frame: 24 months ]
    circulating DNA


Original Secondary Outcome: Same as current

Information By: Gruppo Oncologico Italiano di Ricerca Clinica

Dates:
Date Received: February 17, 2016
Date Started: May 2015
Date Completion: May 2017
Last Updated: February 7, 2017
Last Verified: February 2017