Phase 2
N=34
Bevacizumab, Irinotecan and Temozolomide for Relapsed or Refractory Neuroblastoma
Neuroblastoma
Bottom Line
View on ClinicalTrials.gov: NCT01114555 ↗Enrolled (actual)
34
Serious AEs
41.2%
Results posted
Nov 2019
Primary outcome: Primary: Overall Responses — 3; 18; 12; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Bevacizumab, Irinotecan and Temozolomide (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Primary completion
- Nov 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Responses |
3; 18; 12; 1 | — |
| SECONDARY Number of Participants With Treatment Related Toxicity |
34 | — |
| SECONDARY To Evaluate Changes in Angiogenic Markers After Treatment With the Combination of Irinotecan, Temozolomide and Bevacizumab. |
— | — |
| SECONDARY To Measure Time to Progression in Patients With Resistant NB Treated With the Combination of Irinotecan, Temozolomide and Bevacizumab. |
— | — |
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. 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.
Eligibility Criteria
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 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.
Data sourced from ClinicalTrials.gov (NCT01114555). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.