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N2007-02:Bevacizumab,Cyclophosphamide,& Zoledronic Acid in Patients W/ Recurrent or Refractory High-Risk Neuroblastoma
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
| Neuroblastoma | Drug: Bevacizumab Drug: cyclophosphamide Drug: zoledronic acid | Phase 1 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: No masking Primary Purpose: Treatment |
| Official Title: | A Phase I Study of Bevacizumab With Bolus and Metronomic Cyclophosphamide and Zoledronic Acid in Children With Recurrent or Refractory Neuroblastoma |
- 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. [ Time Frame: Study entry, day 14 of course 1, prior to course 2, day 14 of course 2. ]Any dose limiting toxicity (DLT) as defined in section 9.2 of protocol.
- Evaluation of response within the confines of a phase I study. [ Time Frame: Before study treatment, prior to courses 3 and 6 and then after every 3rd subsequent course. ]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. [ 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. ]Biologic studies will be done to analyse circulating endothelial cells(CEC), circulating precursor cells (CEP)and assessment of markers of bone metabolism.
| Estimated Enrollment: | 36 |
| Study Start Date: | December 2009 |
| Estimated Study Completion Date: | November 2017 |
| Primary Completion Date: | April 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Treatment
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. |
Drug: 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.
Other Names:
Drug: cyclophosphamide
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).
Other Names:
Drug: zoledronic acid
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.
Other Names:
|
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.
Eligibility| Ages Eligible for Study: | up to 30 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00885326
| United States, California | |
| Children's Hospital Los Angeles | |
| Los Angeles, California, United States, 90027-0700 | |
| Lucile Packard Children's Hospital at Stanford University Medical Center | |
| Palo Alto, California, United States, 94304 | |
| UCSF Helen Diller Family Comprehensive Cancer Center | |
| San Francisco, California, United States, 94143 | |
| United States, Georgia | |
| Children's Healthcare of Atlanta | |
| Atlanta, Georgia, United States, 30322 | |
| United States, Illinois | |
| University of Chicago Comer Children's Hospital | |
| Chicago, Illinois, United States, 60637 | |
| United States, Massachusetts | |
| Children's Hospital Boston | |
| Boston, Massachusetts, United States, 02115 | |
| United States, Michigan | |
| C.S Mott Children's Hospital | |
| Ann Arbor, Michigan, United States, 48109 | |
| United States, North Carolina | |
| Duke University Medical Center | |
| Durham, North Carolina, United States, 27710 | |
| United States, Ohio | |
| Cincinnati Children's Hospital Medical Center | |
| Cincinnati, Ohio, United States, 45229-3039 | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | |
| Philadelphia, Pennsylvania, United States, 19104-4318 | |
| United States, Texas | |
| Cook Children's Medical Center - Fort Worth | |
| Fort Worth, Texas, United States, 76104 | |
| Texas Children's Cancer Center | |
| Houston, Texas, United States, 77030-2399 | |
| United States, Washington | |
| Children's Hospital and Regional Medical Center - Seattle | |
| Seattle, Washington, United States, 98105 | |
| Canada, Ontario | |
| Hospital for Sick Children | |
| Toronto, Ontario, Canada, M5G 1X8 | |
| Canada, Quebec | |
| CHU Sainte Justine | |
| Montreal, Quebec, Canada, H3T 1C5 | |
| Principal Investigator: | Julia L. Glade-Bender, MD | Herbert Irving Comprehensive Cancer Center |
More Information
Additional Information:
| Responsible Party: | New Approaches to Neuroblastoma Therapy Consortium |
| ClinicalTrials.gov Identifier: | NCT00885326 History of Changes |
| Other Study ID Numbers: |
CDR0000638257 P01CA081403 ( U.S. NIH Grant/Contract ) |
| Study First Received: | April 18, 2009 |
| Last Updated: | March 23, 2017 |
Keywords provided by New Approaches to Neuroblastoma Therapy Consortium:
|
recurrent neuroblastoma |
Additional relevant MeSH terms:
|
Neuroblastoma Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumors, Primitive Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Bevacizumab Cyclophosphamide Zoledronic acid Diphosphonates |
Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists Bone Density Conservation Agents |
ClinicalTrials.gov processed this record on July 27, 2017