Back to resultsN2007-02:Bevacizumab,Cyclophosphamide,& Zoledronic Acid in Patients W/ Recurrent or Refractory High-Risk Neuroblastoma
Primary Purpose
Neuroblastoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Bevacizumab
cyclophosphamide
zoledronic acid
Sponsored by
About this trial
This is an interventional treatment trial for Neuroblastoma focused on measuring recurrent neuroblastoma
Eligibility Criteria
Inclusion Criteria:
- Patients must be no more 30 years of age when enrolled on study.
- Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to standard treatment.
- Patients who have at least a partial response to standard treatment who still have neuroblastoma that can be seen on CT/MRI or MIBG scans must have a surgical biopsy done of the tumor to confirm that it is neuroblastoma. Patients with relapsed or refractory neuroblastoma do not need to have a biopsy done to enter on study.
- Patients must have adequate heart, kidney, liver blood clotting and bone marrow function. Patients who have bone marrow disease must meet the bone marrow function criteria to enter the study.
- Patients must have recovered from all prior chemotherapy and surgical procedures
Exclusion Criteria:
- They are known to be sensitive to Bevacizumab.
- They have a history of very high blood pressure which required intensive intervention
- They are pregnant or breastfeeding
- Neuroblastoma is present in the brain on a CT or MRI scan done at study entry. Patients with neuroblastoma found in the bones of the skull are eligible if there is no tumor mass associated with them pressing on the brain.
- They have a history non healing wounds
Sites / Locations
- Children's Hospital Los Angeles
- Lucile Packard Children's Hospital at Stanford University Medical Center
- UCSF Helen Diller Family Comprehensive Cancer Center
- Children's Healthcare of Atlanta
- University of Chicago Comer Children's Hospital
- Children's Hospital Boston
- C.S Mott Children's Hospital
- Duke University Medical Center
- Cincinnati Children's Hospital Medical Center
- Children's Hospital of Philadelphia
- Cook Children's Medical Center - Fort Worth
- Texas Children's Cancer Center
- Children's Hospital and Regional Medical Center - Seattle
- Hospital for Sick Children
- CHU Sainte Justine
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Treatment
Arm Description
Bevacizumab: Every course will be 28 days. Bevacizumab 10 mg/kg/dose , will be administered intravenously every 14 days beginning on day 0 of the second course. Cyclophosphamide will be administered as an intravenous (IV) bolus according to the protocol assigned dose level followed by daily oral dosing (25mg/m2/day) without interruption (unless toxicity supervenes). Zoledronic acid will be administered on day 0 of course 1 and day 1 of course 2 and all subsequent courses in a dose of 4mg/m2 (max 4 mg per dose). On days when zoledronic acid (ZA) and cyclophosphamide (CTX) are given together, CTX should be given first.
Outcomes
Primary Outcome Measures
Determination of toxicities and feasibility of the combination of bolus plus metronomic cyclophosphamide and zoledronic acid with and without bevacizumab when given to children with refractory or recurrent high risk neuroblastoma.
Any dose limiting toxicity (DLT) as defined in section 9.2 of protocol.
Secondary Outcome Measures
Evaluation of response within the confines of a phase I study.
Eligible patients are assessed for response after receiving 2 courses OR if they terminate treatment for reasons of toxicity OR if they progress prior to completion of 2 courses of therapy.
Analysis of Circulating Endothelial Cells, Circulating Factors, Gene expression and Bone Metabolism Studies.
Biologic studies will be done to analyse circulating endothelial cells(CEC), circulating precursor cells (CEP)and assessment of markers of bone metabolism.
Full Information
NCT ID
NCT00885326
First Posted
April 18, 2009
Last Updated
April 6, 2023
Sponsor
New Approaches to Neuroblastoma Therapy Consortium
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00885326
Brief Title
N2007-02:Bevacizumab,Cyclophosphamide,& Zoledronic Acid in Patients W/ Recurrent or Refractory High-Risk Neuroblastoma
Official Title
A Phase I Study of Bevacizumab With Bolus and Metronomic Cyclophosphamide and Zoledronic Acid in Children With Recurrent or Refractory Neuroblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
December 2009 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
December 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
New Approaches to Neuroblastoma Therapy Consortium
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Zoledronic acid may stop the growth of tumor cells in bone. Giving bevacizumab together with cyclophosphamide and zoledronic acid may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects of giving bevacizumab together with cyclophosphamide and zoledronic acid in treating patients with recurrent or refractory high-risk neuroblastoma.
Detailed Description
OBJECTIVES:
Primary
To determine the toxicities and feasibility of bolus and metronomic cyclophosphamide when given in combination with zoledronic acid with and without bevacizumab in patients with recurrent or refractory high-risk neuroblastoma.
Secondary
To preliminarily evaluate the antitumor activity of this regimen in these patients within the confines of a pilot study.
OUTLINE: This is a multicenter study.
Patients receive cyclophosphamide IV over 1 hour and zoledronic acid IV over 15 minutes on day 0 and oral cyclophosphamide once daily on days 1-27 in course 1. In course 2 and all subsequent courses, patients receive bevacizumab IV over 30-90 minutes on days 0 and 14, cyclophosphamide IV over 1 hour and zoledronic acid IV over 15 minutes on day 1, and oral cyclophosphamide once daily on days 0 and 2-27. Treatment repeats every 28 days for up to 2 years* in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients may receive up to 13 doses of zoledronic acid.
After completion of study treatment, patients are followed periodically.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma
Keywords
recurrent neuroblastoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Other
Arm Description
Bevacizumab: Every course will be 28 days. Bevacizumab 10 mg/kg/dose , will be administered intravenously every 14 days beginning on day 0 of the second course.
Cyclophosphamide will be administered as an intravenous (IV) bolus according to the protocol assigned dose level followed by daily oral dosing (25mg/m2/day) without interruption (unless toxicity supervenes).
Zoledronic acid will be administered on day 0 of course 1 and day 1 of course 2 and all subsequent courses in a dose of 4mg/m2 (max 4 mg per dose). On days when zoledronic acid (ZA) and cyclophosphamide (CTX) are given together, CTX should be given first.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin, BV
Intervention Description
Every course will be 28 days. Bevacizumab 10 mg/kg/dose , will be administered intravenously every 14 days beginning on day 0 of the second course.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
Cytoxan, CTX
Intervention Description
Cyclophosphamide will be administered as an intravenous (IV) bolus according to the protocol assigned dose level followed by daily oral dosing (25mg/m2/day) without interruption (unless toxicity supervenes).
Intervention Type
Drug
Intervention Name(s)
zoledronic acid
Other Intervention Name(s)
Zometa, ZA
Intervention Description
Administered on day 0 of course 1 and day 1 of course 2 and all subsequent courses in a dose of 4mg/m2 (max 4 mg per dose). On days when zoledronic acid (ZA) and cyclophosphamide (CTX) are given together, CTX should be given first.
Primary Outcome Measure Information:
Title
Determination of toxicities and feasibility of the combination of bolus plus metronomic cyclophosphamide and zoledronic acid with and without bevacizumab when given to children with refractory or recurrent high risk neuroblastoma.
Description
Any dose limiting toxicity (DLT) as defined in section 9.2 of protocol.
Time Frame
Study entry, day 14 of course 1, prior to course 2, day 14 of course 2.
Secondary Outcome Measure Information:
Title
Evaluation of response within the confines of a phase I study.
Description
Eligible patients are assessed for response after receiving 2 courses OR if they terminate treatment for reasons of toxicity OR if they progress prior to completion of 2 courses of therapy.
Time Frame
Before study treatment, prior to courses 3 and 6 and then after every 3rd subsequent course.
Title
Analysis of Circulating Endothelial Cells, Circulating Factors, Gene expression and Bone Metabolism Studies.
Description
Biologic studies will be done to analyse circulating endothelial cells(CEC), circulating precursor cells (CEP)and assessment of markers of bone metabolism.
Time Frame
Will be measured a total of 4 times, prior to start of course and then at day 14 of courses 1 and 2 only.
10. Eligibility
Sex
All
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must be no more 30 years of age when enrolled on study.
Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to standard treatment.
Patients who have at least a partial response to standard treatment who still have neuroblastoma that can be seen on CT/MRI or MIBG scans must have a surgical biopsy done of the tumor to confirm that it is neuroblastoma. Patients with relapsed or refractory neuroblastoma do not need to have a biopsy done to enter on study.
Patients must have adequate heart, kidney, liver blood clotting and bone marrow function. Patients who have bone marrow disease must meet the bone marrow function criteria to enter the study.
Patients must have recovered from all prior chemotherapy and surgical procedures
Exclusion Criteria:
They are known to be sensitive to Bevacizumab.
They have a history of very high blood pressure which required intensive intervention
They are pregnant or breastfeeding
Neuroblastoma is present in the brain on a CT or MRI scan done at study entry. Patients with neuroblastoma found in the bones of the skull are eligible if there is no tumor mass associated with them pressing on the brain.
They have a history non healing wounds
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julia L. Glade-Bender, MD
Organizational Affiliation
Herbert Irving Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027-0700
Country
United States
Facility Name
Lucile Packard Children's Hospital at Stanford University Medical Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
UCSF Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Chicago Comer Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
C.S Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104-4318
Country
United States
Facility Name
Cook Children's Medical Center - Fort Worth
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Texas Children's Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-2399
Country
United States
Facility Name
Children's Hospital and Regional Medical Center - Seattle
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
CHU Sainte Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
N2007-02:Bevacizumab,Cyclophosphamide,& Zoledronic Acid in Patients W/ Recurrent or Refractory High-Risk Neuroblastoma
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