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

Neuroendocrine Carcinomas Clinical Trial

— XELBEVOCT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01203306
• Other study ID #: EudraCT 2006-004748-22
• Status: Recruiting
• Phase: Phase 2
• First received: September 9, 2010
• Last updated: September 15, 2010
• Start date: January 2006
• Est. completion date: December 2010

Study information

• Verified date: July 2010
• Source: University of Turin, Italy
• Contact: Maria P Brizzi, MD, PhD
• Phone: +39, 011-9026
• Email: mariapia.brizzi[@]email.it
• Is FDA regulated: No
• Health authority: Italy: AIFA - The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: December 2010
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Carcinoid Tumor
• Carcinoma, Neuroendocrine
• Neuroendocrine Carcinomas
• Neuroendocrine Tumors

Intervention

Drug:
• bevacizumab + octreotide LAR + capecitabine
long acting octreotide acetate at a dose of 20 or 30 mg administered intramuscularly every 4 weeks; Bevacizumab at a dose of 5 mg/kg every 2 weeks; orally capecitabine administered at a dose of 2000 mg/daily

Locations

Country	Name	City	State
Italy	Elisabetta Nobili	Bologna
Italy	Nicola Fazio	Milan
Italy	Anna Ferrero	Orbassano	Turin
Italy	Lucia Tozzi	San Giovanni Rotondo	Foggia
Italy	Enrica Milanesi	Turin

Sponsors (1)

Lead Sponsor	Collaborator
University of Turin, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	time to progression		36 months	Yes
Secondary	Toxicity	All adverse events encountered during the clinical study will be reported. The intensity of clinical adverse events will be graded according to the NCI Common Toxicity Criteria (CTC) version 3.0 grading system.	two years	Yes
Secondary	Time to Treatment Failure (TTF)	TTF is the time from first day of treatment to the first occurrence of any adverse events with withdrew prematurely the treatment.	two years	Yes
Secondary	Overall survival (OS)	Overall survival (OS) will be computed as the time between the first day of treatment and the date of death or the last date the patient was known to be alive.	48 months	Yes