NeuroblastomaPhase 2NCT01114555
Bevacizumab, Irinotecan and Temozolomide for Relapsed or Refractory Neuroblastoma
A Phase 2 study testing Bevacizumab, Irinotecan and Temozolomide in people with Neuroblastoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Bevacizumab, Irinotecan and Temozolomide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Apr 2010to 2 Nov 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
About this study
Official title: 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.
- Conditions
- Neuroblastoma
- Being tested
- Bevacizumab, Irinotecan and Temozolomide
- Keywords
- Bevacizumab, Irinotecan, Temozolomide, 10-015
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab, Irinotecan and TemozolomideDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab, Irinotecan and Temozolomide | Experimental | This is a phase II study of the combination of irinotecan, temozolomide and bevacizumab in patients with resistant NB. Receives: Drug: Bevacizumab, Irinotecan and Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Responses
To evaluate tumor responses to combination of irinotecan, temozolomide and bevacizumab in patients with resistant NB.
Measured: 15-35 days after cycle 2
Secondary outcomes (3)
Number of Participants With Treatment Related Toxicity
To determine the toxicity of the combination of irinotecan, temozolomide and bevacizumab in patients with resistant NB.
Measured: Patients will be evaluated at least once weekly for toxicity. Observation for toxicities for up to 42 days
To Evaluate Changes in Angiogenic Markers After Treatment With the Combination of Irinotecan, Temozolomide and Bevacizumab.
Measured: days 1,4, 15 and once between days 22-35 during cycle 1 and cycle 2
To Measure Time to Progression in Patients With Resistant NB Treated With the Combination of Irinotecan, Temozolomide and Bevacizumab.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2010 (estimated)
- Study start29 Apr 2010
- Primary completion2 Nov 2018
- Study completion2 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Shakeel Modak, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01114555
- Sponsor's protocol ID
- 10-015
- Status last verified
- Nov 2018
- First submitted
- 29 Apr 2010
- Last updated
- 21 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Modak S, Kushner BH, Basu E, Roberts SS, Cheung NK. Combination of bevacizumab, irinotecan, and temozolomide for refractory or relapsed neuroblastoma: Results of a phase II study. Pediatr Blood Cancer. 2017 Aug;64(8):10.1002/pbc.26448. doi: 10.1002/pbc.26448. Epub 2017 Jan 23.
PubMed 28111925
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination of Bevacizumab, Irinotecan and Temozolomide for Relapsed or Refractory Neuroblastoma: A Phase II Study
- ClinicalTrials.gov ID
- NCT01114555
- Acronym / sponsor ID
- 10-015
- Conditions
- Neuroblastoma
- Keywords
- Bevacizumab, Irinotecan, Temozolomide, 10-015
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 29 Apr 2010 (actual)
- Primary completion
- 2 Nov 2018 (actual)
- Study completion
- 2 Nov 2018 (actual)
- First posted
- 3 May 2010 (estimated)
- Results
- Posted 13 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab, Irinotecan and Temozolomide | Experimental | Drug: Bevacizumab, Irinotecan and TemozolomideThis is a phase II study of the combination of irinotecan, temozolomide and bevacizumab in patients with resistant NB. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bevacizumab, Irinotecan and TemozolomidePatients 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). | Drug | Bevacizumab, Irinotecan and Temozolomide |
Primary outcome
Overall Responses
Time frame: 15-35 days after cycle 2
To evaluate tumor responses to combination of irinotecan, temozolomide and bevacizumab in patients with resistant NB.
3 secondary outcomes
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
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
To Measure Time to Progression in Patients With Resistant NB Treated With the Combination of Irinotecan, Temozolomide and Bevacizumab.
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28111925Modak S, Kushner BH, Basu E, Roberts SS, Cheung NK. Combination of bevacizumab, irinotecan, and temozolomide for refractory or relapsed neuroblastoma: Results of a phase II study. Pediatr Blood Cancer. 2017 Aug;64(8):10.1002/pbc.26448. doi: 10.1002/pbc.26448. Epub 2017 Jan 23.
- Memorial Sloan-Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shakeel Modak, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab, Irinotecan and Temozolomide in people with Neuroblastoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Responses (time frame: 15-35 days after cycle 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01114555, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2019.