Bevacizumab Plus Somatostatin Analogue and Metronomic Capecitabine in Patients With Advanced Neuroendocrine Tumors

Condition(s) targeted: Neuroendocrine Carcinomas

Intervention: bevacizumab + octreotide LAR + capecitabine (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Turin, Italy

Official(s) and/or principal investigator(s):
Alfredo Berruti, MD, PhD, Study Director, Affiliation: Medical Oncology, Department of Clinical and Biological Sciences, University of Turin

Overall contact:
Maria P Brizzi, MD, PhD, Phone: +39, 011-9026, Ext: 007, Email: mariapia.brizzi@email.it

Well differentiated neuroendocrine (NE) 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 and antiangiogenetic drugs. This is a national, multicenter, phase II study.

Official title: Phase II Study of the Combination of Bevacizumab Plus Somatostatin Analogue and Metronomic Capecitabine in Patients With Advanced Inoperable Well-Differentiated Neuroendocrine Tumors

Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: time to progression

Secondary outcome:

Toxicity

Time to Treatment Failure (TTF)

Overall survival (OS)

Detailed description: Metastatic or locally advanced well differentiated neuroendocrine carcinoma will be treated with a combination of bevacizumab (5 mg/kg) plus octreotide LAR (long- acting release) 20/30 mg plus capecitabine administered on a metronomic schedule (2000 mg/day).

Patients with stable disease, complete or partial response will continue treatment until progressive disease or unacceptable toxicity.

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

Secondary endpoint: - 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);

- relationship between vascular endothelial growth factor (VEGF) polymorphisms and

response to treatment;

- time to progression and survival: measured from the date of treatment start to the date

of progression and the date of last follow-up or death, respectively.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Histologically or cytologically diagnosis of well-differentiated neuroendocrine

carcinoma

- Inoperable disease

- Age > 18

- ECOG Performance Status 0-2

- Life expectancy of at least 12 weeks

- Measurable and/or evaluable lesions according to RECIST criteria

- Radiological documentation of disease progression

- Adequate bone marrow reserve

- Adequate hepatic and renal function

- Urine dipstick of proteinuria < 2+

- Written informed consent

- Comply with the protocol procedures

Exclusion criteria:

- Serious non-healing wound or ulcer

- Evidence of bleeding diathesis or coagulopathy

- Uncontrolled hypertension

- Clinically significant cardiovascular disease for example cerebrovascular accidents

(≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication

- Current or recent ongoing treatment with anticoagulants for therapeutic purposes

- Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications

known to predispose to gastrointestinal ulceration

- Patients with severe renal impairment (creatinine clearance below 30 ml/min)

- Other co-existing malignancies or malignancies diagnosed within the last 5 years with

the exception of basal cell carcinoma or cervical cancer in situ

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days

prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study

- Pregnant or lactating women.

Maria P Brizzi, MD, PhD, Phone: +39, 011-9026, Ext: 007, Email: mariapia.brizzi@email.it

Elisabetta Nobili, Bologna 40138, Italy; Recruiting
Elisabetta Nobili, MD, Phone: 051 6363, Ext: 680, Email: elisabetta.nobili3@unibo.it
Guido Biasco, MD, PhD, Principal Investigator

Nicola Fazio, Milan 20121, Italy; Completed

Enrica Milanesi, Turin 10126, Italy; Completed

Lucia Tozzi, San Giovanni Rotondo, Foggia 71013, Italy; Completed

Anna Ferrero, Orbassano, Turin 10043, Italy; Recruiting
Anna Ferrero, MD, Phone: +39 011 9026, Ext: 526, Email: anna.ferrero80@libero.it
Maria P Brizzi, MD, PhD, Sub-Investigator

Related publications:

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.

Starting date: January 2006
Last updated: September 15, 2010