Clinical trial NCT00953394: 5FU and Octreotide Long-acting Release (LAR) for Neuroendocrine Tumors
Official title: Continuous 5-fluorouracil Infusion Plus Long Acting Octreotide in Advanced Well Differentiated Neuroendocrine Carcinomas. A Phase II Trial of the Piemonte Oncology Network.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Tumors
Keywords: octreotide LAR
neuroendocrine carcinoma
metronomic 5fluorouracil
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
First posted: 2009-08-06
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Well differentiated neuroendocrine carcinomas have low proliferative activity and conventional chemotherapy is not recommended. Metronomic chemotherapy, i.e. the frequent administration of cytotoxic drugs at low doses, has demonstrated antiangiogenetic properties. Since well differentiated NE carcinomas are highly vascular, there is a rationale for testing metronomic chemotherapy in this clinical setting.

A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide for patients with neuroendocrine carcinoma.

Detailed description: Metastatic or locally advanced well differentiated neuroendocrine carcinoma were treated with 5Fluorouracil protracted intravenous infusion (200 mg/m2 daily) plus Octreotide LAR (20 mg monthly).

Primary Endpoint: the response to treatment, evaluated according to the RECIST criteria.

Secondary Endpoints:

* toxicity, graded according to the NCI-CTG criteria;
* symptomatic response: evaluated according to the changes in both the frequency and intensity of symptoms;
* biochemical response: evaluated considering the changes in the tumor marker levels (circulating Chromogranin A);
* time to progression and survival: were measured from the date of treatment start to the date of progression and the date of last follow-up or death, respectively.

Eligibility criteria: Inclusion Criteria:

* histological diagnosis of well-differentiated neuroendocrine carcinoma according to the World Health Organization (WHO) classification;
* locally advanced or metastatic disease not amenable to surgery with radical intent;
* at least one measurable target lesion;
* radiological documentation of progressive disease;
* ECOG performance status grade \<=2;
* life expectancy \>12 weeks;
* adequate bone marrow reserve;
* adequate hepatic and renal function;
* ability to comply with the protocol procedures (including geographic accessibility);
* written informed consent.

Exclusion Criteria:

* non-malignant systemic disease or conditions that precluded patients from receiving the study therapy;
* second primary malignancies and previous systemic antineoplastic treatment including somatostatin analogues;
* history of prior malignancy, excepted for cured non-melanoma skin cancer, and cured in situ cervical carcinoma.

Primary outcomes:
measure: disease free survival
timeFrame: 50 months
Secondary outcomes:
Other outcomes:
Locations:
city: Alba
country: Italy
facility: Federico Castiglione
state: Cuneo
city: Saluzzo
country: Italy
facility: Davide Perroni
state: Cuneo
city: San Severino Marche
country: Italy
facility: Benedetta Ferretti
state: Macerata
city: Ivrea
country: Italy
facility: Sebastiano Bombaci
state: Torino
city: Orbassano
country: Italy
facility: Anna Ferrero
state: Torino
city: Novara
country: Italy
facility: Oscar Alabiso
city: Torino
country: Italy
facility: Enrica Milanesi
Study officials:
affiliation: Medical oncology, Department of Clinical and Biological Sciences, University of Turin
name: Alfredo Berruti, PHD
role: STUDY_CHAIR
affiliation: Medical oncology, Department of Clinical and Biological Sciences, University of Turin
name: Luigi Dogliotti, PHD
role: STUDY_DIRECTOR
affiliation: Centro Oncologico Ematologico Subalpino, Azienda Ospedaliera Molinette, Torino
name: Libero Ciuffreda, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brizzi MP, Berruti A, Ferrero A, Milanesi E, Volante M, Castiglione F, Birocco N, Bombaci S, Perroni D, Ferretti B, Alabiso O, Ciuffreda L, Bertetto O, Papotti M, Dogliotti L. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte oncology network. BMC Cancer. 2009 Nov 3;9:388. doi: 10.1186/1471-2407-9-388.