- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01114555
Bevacizumab, Irinotecan and Temozolomide for Relapsed or Refractory Neuroblastoma
November 12, 2019 updated by: Memorial Sloan Kettering Cancer Center
Combination of Bevacizumab, Irinotecan and Temozolomide for Relapsed or Refractory Neuroblastoma: A Phase II Study
The purpose of this study is to find how good and how safe the combination of irinotecan, temozolomide and bevacizumab is for patients with resistant or recurrent neuroblastoma.
These drugs have each been given separately to patients, but they have never been given all together.
Irinotecan and temozolomide are two drugs that have been used together to treat neuroblastoma in many people.
These drugs are considered chemotherapy.
Bevacizumab is another drug used to treat cancer.
It is made by a company called Genentech.
Bevacizumab is an antibody.
Antibodies are proteins that are found in the blood and can attach themselves to bacteria and viruses.
Bevacizumab attaches itself to a special protein in the bloodstream.
This protein helps tumors grow new blood vessels.
Blood vessels carry nutrients to feed the tumor.
Bevacizumab is thought to block this growth of new blood vessels and starve tumors.
It has been used for the treatment of many cancers in adults.
It is approved by the FDA for the treatment of adults with colon cancer and other cancers but not for people with neuroblastoma.
There is only a small amount of information known on using this drug in children.
It has been used with irinotecan before to treat cancer but not in children with neuroblastoma.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
34
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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New York
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New York, New York, United States, 10021
- Memorial Sloan Kettering Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients must have the diagnosis of NB in accordance with the International Criteria, i.e., either histopathology (confirmed by the MSKCC Department of Pathology) or BM involvement plus elevated urinary catecholamines.
- Must have a history of tumor progression or recurrence or failure to achieve complete response with standard therapy.
- Patients must have evaluable (microscopic marrow metastasis, MIBG or PET scans) or measurable (CT, MRI) disease.
- Patients of all ages are eligible.
- Prior Therapy: At least 2 weeks should have elapsed since any biologic therapy. Three weeks should have elapsed since last dose of chemotherapy.
- Minimum life expectancy of eight weeks.
- Signed informed consent indicating awareness of the investigational nature of this program.
Exclusion Criteria:
- Severe major organ toxicity. Renal, cardiac, hepatic, pulmonary, gastrointestinal and neurologic toxicity should all be grade 2 or less (per NCI CTC version 4.0 criteria). Specifically, serum creatinine should be ≤3 x upper limit of normal (ULN), serum AST and ALT ≤5 x ULN, serum bilirubin ≤ 3 x ULN, LV shortening fraction should be ≥15%.
- Patients with myelosuppression are not excluded if ANC ≥ 500/uL. Platelet count should be > 35,000/ul and hemoglobin should be > 8gm/dl. Patients should not have received filgrastim, platelet or red blood cell transfusions for 2 days prior to achieving the above ANC, platelet and hemoglobin levels.
- Patients with documented chronic non-healing wound, ulcer or bone fracture
- Surgical procedures.
- Patients who have undergone major surgery <28 days prior to beginning therapy with bevacizumab are excluded.
- Patients must be least 24 hours from having after surgical procedures such as placement of central catheter.
- Patients <7days from minor surgeries (e.g. fine needle or core biopsies) and/or the unhealed wounds from these procedures are excluded.
- Patients will be excluded if major surgery (e.g. abdominal or thoracic surgery for resection of tumor) is anticipated during the course of the study.
- Known bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
- Thrombosis: patients must not have had a deep venous or arterial thrombosis (non-central venous catheter related) within the last three months prior to study entry. Patients with cerebrovascular accident or transient ischemic attack within 6 months of therapy are excluded. Patients with history of peripheral vascular disease, myocardial infarction or unstable angina are excluded.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study entry.
- Known CNS metastases, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement except for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include radiotherapy, chemotherapy or immunotherapy Patients with CNS metastases treated by neurosurgical resection or biopsy performed within 3 months of treatment will be excluded.
- Proteinuria: Urine protein: creatinine ratio ≥ 1.0.
- Uncontrolled (lasting >24 hrs on antihypertensive medication) hypertension as defined by age-appropriate criteria. Hypertension is defined as average systolic blood pressure and/or diastolic blood pressure that is 95th percentile for gender, age, and height on 3 occasions93. 95th percentiles for gender, age and height are provided in Appendix A. For patients ≥18 years of age, hypertension is defined as systolic blood pressure >150mmHg and/or diastolic blood pressure >100mmHg.
- Prior history of hypertensive crisis or hypertensive encephalopathy
- History of hypersensitivity to any component of bevacizumab
- History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1.
- Active serious infections not controlled by antibiotics.
- Pregnant women are excluded for fear of danger to the fetus. Therefore negative pregnancy test is required for all women of child-bearing age, and appropriate contraception is used during the study period.
- Inability or unwillingness to comply with protocol requirements.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Bevacizumab, Irinotecan and Temozolomide
This is a phase II study of the combination of irinotecan, temozolomide and bevacizumab in patients with resistant NB.
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Patients will initially receive bevacizumab IV at 15mg/kg/dose (this is defined as Day 1 Three days later (starting day 4), they will receive concurrently, IV irinotecan at 50mg/m2/day x 5 days plus PO temozolomide 150mg/m2/day x 5 days.
A second dose of bevacizumab will be administered 14 days after the first one(day 15).
The treatment schedule may require minor adjustment as clinically indicated (e.g., due to PDH closure for holidays).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Responses
Time Frame: 15-35 days after cycle 2
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To evaluate tumor responses to combination of irinotecan, temozolomide and bevacizumab in patients with resistant NB.
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15-35 days after cycle 2
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment Related Toxicity
Time Frame: Patients will be evaluated at least once weekly for toxicity. Observation for toxicities for up to 42 days
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To determine the toxicity of the combination of irinotecan, temozolomide and bevacizumab in patients with resistant NB.
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Patients will be evaluated at least once weekly for toxicity. Observation for toxicities for up to 42 days
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To Evaluate Changes in Angiogenic Markers After Treatment With the Combination of Irinotecan, Temozolomide and Bevacizumab.
Time Frame: days 1,4, 15 and once between days 22-35 during cycle 1 and cycle 2
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days 1,4, 15 and once between days 22-35 during cycle 1 and cycle 2
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To Measure Time to Progression in Patients With Resistant NB Treated With the Combination of Irinotecan, Temozolomide and Bevacizumab.
Time Frame: 3 years
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3 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 29, 2010
Primary Completion (Actual)
November 2, 2018
Study Completion (Actual)
November 2, 2018
Study Registration Dates
First Submitted
April 29, 2010
First Submitted That Met QC Criteria
April 30, 2010
First Posted (Estimate)
May 3, 2010
Study Record Updates
Last Update Posted (Actual)
November 21, 2019
Last Update Submitted That Met QC Criteria
November 12, 2019
Last Verified
November 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroectodermal Tumors, Primitive
- Neuroectodermal Tumors, Primitive, Peripheral
- Neuroblastoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Topoisomerase I Inhibitors
- Temozolomide
- Bevacizumab
- Irinotecan
Other Study ID Numbers
- 10-015
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Neuroblastoma
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Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingStage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 2A Neuroblastoma | Stage 2B Neuroblastoma | Stage 3 Neuroblastoma | Stage 4 Neuroblastoma | Stage 1 Neuroblastoma | Stage 2 NeuroblastomaUnited States, Canada, Australia, New Zealand
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Disseminated Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S NeuroblastomaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 4 NeuroblastomaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingRecurrent Neuroblastoma | Stage 4S Neuroblastoma | Stage 2A Neuroblastoma | Stage 2B Neuroblastoma | Stage 3 Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand
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National Cancer Institute (NCI)Active, not recruitingRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand, Puerto Rico
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)RecruitingLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 4 NeuroblastomaUnited States, Puerto Rico, Canada, Australia, New Zealand, Netherlands, Saudi Arabia, Switzerland
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4 NeuroblastomaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Disseminated Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Stage 4S NeuroblastomaUnited States
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