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

Primary Purpose

Neuroendocrine Carcinomas

Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
bevacizumab + octreotide LAR + capecitabine
Sponsored by
University of Turin, Italy
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroendocrine Carcinomas focused on measuring bevacizumab, somatostatin analogue, metronomic capecitabine, neuroendocrine tumors

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Lucia Tozzi
  • Anna FerreroRecruiting
  • Elisabetta NobiliRecruiting
  • Nicola Fazio
  • Enrica Milanesi

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Drugs: bevacizumab + octreotide LAR + capecitabine

Arm Description

bevacizumab + octreotide + metronomic capecitabine

Outcomes

Primary Outcome Measures

time to progression

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
September 9, 2010
Last Updated
September 15, 2010
Sponsor
University of Turin, Italy
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1. Study Identification

Unique Protocol Identification Number
NCT01203306
Brief Title
Bevacizumab Plus Somatostatin Analogue and Metronomic Capecitabine in Patients With Advanced Neuroendocrine Tumors
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2010
Overall Recruitment Status
Unknown status
Study Start Date
January 2006 (undefined)
Primary Completion Date
May 2009 (Anticipated)
Study Completion Date
December 2010 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
University of Turin, Italy

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Carcinomas
Keywords
bevacizumab, somatostatin analogue, metronomic capecitabine, neuroendocrine tumors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Drugs: bevacizumab + octreotide LAR + capecitabine
Arm Type
Experimental
Arm Description
bevacizumab + octreotide + metronomic capecitabine
Intervention Type
Drug
Intervention Name(s)
bevacizumab + octreotide LAR + capecitabine
Other Intervention Name(s)
Avastin, Sandostatin LAR, Xeloda
Intervention Description
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
Primary Outcome Measure Information:
Title
time to progression
Time Frame
36 months
Secondary Outcome Measure Information:
Title
Toxicity
Description
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.
Time Frame
two years
Title
Time to Treatment Failure (TTF)
Description
TTF is the time from first day of treatment to the first occurrence of any adverse events with withdrew prematurely the treatment.
Time Frame
two years
Title
Overall survival (OS)
Description
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.
Time Frame
48 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maria P Brizzi, MD, PhD
Phone
+39, 011-9026
Ext
007
Email
mariapia.brizzi@email.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alfredo Berruti, MD, PhD
Organizational Affiliation
Medical Oncology, Department of Clinical and Biological Sciences, University of Turin
Official's Role
Study Director
Facility Information:
Facility Name
Lucia Tozzi
City
San Giovanni Rotondo
State/Province
Foggia
ZIP/Postal Code
71013
Country
Italy
Individual Site Status
Completed
Facility Name
Anna Ferrero
City
Orbassano
State/Province
Turin
ZIP/Postal Code
10043
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Ferrero, MD
Phone
+39 011 9026
Ext
526
Email
anna.ferrero80@libero.it
First Name & Middle Initial & Last Name & Degree
Maria P Brizzi, MD, PhD
Facility Name
Elisabetta Nobili
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elisabetta Nobili, MD
Phone
051 6363
Ext
680
Email
elisabetta.nobili3@unibo.it
First Name & Middle Initial & Last Name & Degree
Guido Biasco, MD, PhD
Facility Name
Nicola Fazio
City
Milan
ZIP/Postal Code
20121
Country
Italy
Individual Site Status
Completed
Facility Name
Enrica Milanesi
City
Turin
ZIP/Postal Code
10126
Country
Italy
Individual Site Status
Completed

12. IPD Sharing Statement

Citations:
PubMed Identifier
19886987
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.
Results Reference
background
PubMed Identifier
24628963
Citation
Berruti A, Fazio N, Ferrero A, Brizzi MP, Volante M, Nobili E, Tozzi L, Bodei L, Torta M, D'Avolio A, Priola AM, Birocco N, Amoroso V, Biasco G, Papotti M, Dogliotti L. Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the XELBEVOCT study. BMC Cancer. 2014 Mar 14;14:184. doi: 10.1186/1471-2407-14-184.
Results Reference
derived

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

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