A Phase II Trial of Cyclophosphamide, Topotecan, and Bevacizumab (CTB) in Patients With Relapsed/Refractory Ewing's Sarcoma and Neuroblastoma
Overview
- Phase
- Phase 2
- Intervention
- Cyclophosphamide, Topotecan, and Bevacizumab
- Conditions
- Neuroblastoma
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 9
- Locations
- 7
- Primary Endpoint
- Objective Response Rate
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to find out what effects, good and/or bad treatment with a new combination of drugs, cyclophosphamide, topotecan, and bevacizumab has on the patient and their cancer.
The medications, cyclophosphamide and topotecan, are standard drugs often used together for the treatment of cancer in children with either Ewing's sarcoma or neuroblastoma.
Bevacizumab is an experimental drug called an antibody that targets a protein important in the growth of cancer cells called vascular endothelial growth factor (VEGF). VEGF is made by tumor and other surrounding cells to help make blood vessels needed for the growth and spread of cancer cells in the body. The way that bevacizumab works is to stop the cancer cells from making their own blood supply, causing the tumor to stop growing bigger or from spreading. In adult clinical trials, bevacizumab has shown promising anti-cancer activity in patients with cancer of the colon/rectum (colorectal) and breast. It has been approved by the Food and Drug Administration (FDA) for use in patients with colorectal cancer but not in cancers found in children. Bevacizumab has been tested in early clinical studies in children and has been shown to be safe.
Other goals of this study will include research tests designed to test the following changes in the patient or their cancer: to see how the body handles and breaks down bevacizumab (pharmacokinetics), to look at changes in proteins in the blood that may affect the way the cancer responds to the combination (angiogenic profile, angiogenesis associated serum biomarkers), to look at changes in genes that may affect how the cancer responds to treatment with this combination of medications (metabolic signature), and to monitor the effects of changes in the way the body grows and develops before and after bevacizumab is given.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically confirmed relapsed/refractory Ewing's sarcoma or neuroblastoma.
- •Patients must have measurable disease. Patients with a diagnosis of neuroblastoma with MIBG avid disease only are permitted to enroll on this study.
- •Patients must be ≤ 21 years of age at time of diagnosis
- •Life expectancy ≥ 3 months
- •Lansky or Karnofsky performance ≥ 70%
- •Written informed consent
- •Organ and marrow function defined as follows:
- •Hematologic function, as follows
- •Absolute neutrophil count ≥ 1000/μL
- •Platelets ≥ 100 x 109/L (without transfusion \< 14 days before enrollment) Hemoglobin ≥ 9 gm/dl
Exclusion Criteria
- •Patients with centrally-located pulmonary or mediastinal primary tumors or metastases adjacent to or invading large blood vessels.
- •Prior left chest wall irradiation or a cumulative anthracycline dose of greater or equal to 300 mg/m2, unless the ejection fraction or fraction shortening is within normal institutional limits, in which case the patient can be enrolled.
- •Inability to comply with study and/or follow-up procedures
- •Life expectancy of less than 3 months
- •Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
- •Active second malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years
- •History of other malignancies, except for other solid tumors curatively treated with no evidence of disease for \> 3 years prior to enrollment.
- •Known infection with human immunodeficiency virus (HIV).
- •Uncontrolled hypertension (sBP \>150 mmHg and/or diastolic BP \> 100 mmHg, found on two consecutive measurements separated by a one week period of time despite adequate medical support).
- •Prior history of hypertensive crisis or hypertensive encephalopathy.
Arms & Interventions
Cyclophosphamide, Topotecan, and Bevacizumab (CTB)
This is a multi-center, open label phase II study evaluating the safety and efficacy of the novel combination of agents consisting of bevacizumab, cyclophosphamide, and topotecan.
Intervention: Cyclophosphamide, Topotecan, and Bevacizumab
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: 2 years
as measured by objective response rate (CR/PR) after 2 cycles of treatment and duration of response. after 2 cycles of treatment and duration of response according to the Revised RECIST guideline (version 1.1) Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Secondary Outcomes
- Number of Participants With Adverse Events(2 years)