Carboplatin and Bevacizumab for Recurrent Ependymoma
- Conditions
- Anaplastic EpendymomaEpendymoma
- Interventions
- Registration Number
- NCT01295944
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
The goal of this clinical research study is to learn if the combination of bevacizumab and carboplatin can help to control recurrent ependymoma. The safety of this drug combination will also be studied.
- Detailed Description
Background:
* Ependymomas are glial based tumors arising from the ependymal lining of the ventricular system and central canal of the spinal cord
* These tumors affect both adults and children and represent approximately 1.2%-7.8% of all intracranial cancers.
* Currently, the standard therapy for newly diagnosed low-grade ependymoma includes total surgical excision, when possible, followed by radiation therapy. Complete surgical resection is often not possible because of the location of the tumor and the concern for damage to surrounding eloquent brain during surgery. The situation is even more critical for patients with anaplastic ependymomas because of the higher proliferative rate and greater propensity for tumor infiltration into surrounding normal brain, preventing any possibility of complete tumor removal by surgery.
* For patients with the more aggressive anaplastic ependymoma, chemotherapy is often administered either before or after the radiation in the hope that infiltrating tumor cells will be eliminated.
* Extensive experience has been gathered with the use of bevacizumab in other neuroepithelial tumors such as malignant gliomas. Based on the interesting results observed in the reported small series of patients with recurrent ependymomas treated with bevacizumab, as well as on the evidence of vascular endothelial growth factor (VEGF)-promoted angiogenesis in these tumors, we designed a phase II study to test the efficacy of bevacizumab in patients with recurrent ependymoma. As results in most types of tumors have indicated that anti-angiogenesis therapies are more effective when given in combination with cytotoxic chemotherapy, in this study bevacizumab will be combined with carboplatin. The choice of carboplatin is justified by the fact that, as detailed above, this remains the most effective agent in this disease, and extensive toxicity data is available for the combination of bevacizumab and carboplatin in a variety of tumor types, including glioblastomas (GBMs).
Objective:
To evaluate the efficacy of carboplatin and bevacizumab for the treatment of recurrent low grade or anaplastic ependymoma. The primary endpoint will be progression-free survival (PFS) at one year.
Design:
* This is a phase II study to evaluate the efficacy of carboplatin and bevacizumab for the treatment of recurrent low grade or anaplastic ependymoma. This trial is designed utilizing a Simon optimal two-stage design.
* Carboplatin will be given on day 1 of each cycle. Bevacizumab will be administered on days 1 and 15 of each cycle. The total duration of treatment will be 6 cycles. After cycle 6, carboplatin should be discontinued, but bevacizumab may be continued at the discretion of the treating physician.
* Patients will be monitored for hematologic or serologic evidence of myelosuppression, hepatic injury, renal injury, and electrolyte disturbances and for clinical evidence of other toxicity.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1/Carboplatin and Bevacizumab for Recurrent Ependymoma Bevacizumab The total duration of treatment will be 6 cycles. After cycle 6, carboplatin should be discontinued, but bevacizumab may be continued at the discretion of the treating physician. 1/Carboplatin and Bevacizumab for Recurrent Ependymoma Carboplatin The total duration of treatment will be 6 cycles. After cycle 6, carboplatin should be discontinued, but bevacizumab may be continued at the discretion of the treating physician.
- Primary Outcome Measures
Name Time Method Percentage of Participants That Have Progressive Free Survival (PFS) After 1 Year 1 year Percentage of participants that have progressive disease after 1 year. Kaplan-Meier method is used for the analyses of PFS. Progression is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline. Clear worsening of any evaluable disease, or appearance of any new lesion/site, clear clinical worsening or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
- Secondary Outcome Measures
Name Time Method Number of Participants With a (Complete Response (CR) + Partial Response (PR)) Up to 6 months and 1 week Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) is complete disappearance of all measurable and evaluable disease. No new lesions. Partial Response (PR) is greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions.
Overall Survival (OS) The time from treatment start date until date of death or date last known alive, up to 68 months OS was calculated by the Kaplan Meier methodology. OS is defined as the time from treatment start date until date of death or date last known alive.
Mean Core Symptom Severity With Daily Activities Using the MD Anderson Symptom Inventory for Brain Tumors (MDASI-BT) Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 2, cycle 4, and cycle 6 (each cycle is 28 days) The MDASI-BT consists of 23 symptoms rated on an 11 point scale (0 - not present, to 10 - as bad as you can imagine) to indicate the presence and severity of the symptom. All participants with at least one valid questionnaire are included in the analyses. We calculated the mean core symptom severity score rated on the scale from 0-not present to 10-as bad as you can imagine at the time of clinical evaluation. Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom severity measures. For example, an increase of 2 points or more would mean a moderate improvement, whereas a decrease of 2 points or more would be interpreted as moderate worsening.
Mean Core Symptom Severity With Daily Activities Using the MD Anderson Symptom Inventory for Spine Tumors (MDASI-SP) Instrument Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 2, cycle 4, and cycle 6 (each cycle is 28 days) The MDASI-SP consists of 23 symptoms rated on an 11 point scale (0 - not present, to 10 - as bad as you can imagine) to indicate the presence and severity of the symptom. All participants with at least one valid questionnaire are included in the analyses. We calculated the mean core symptom severity score rated on the scale from 0-not present to 10-as bad as you can imagine at the time of clinical evaluation. Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom severity measures. For example, an increase of 2 points or more would mean a moderate improvement, whereas a decrease of 2 points or more would be interpreted as moderate worsening.
Mean Symptom Interference With Daily Activities Using the MD Anderson Symptom Inventory for Brain Tumors (MDASI-BT) Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 2, cycle 4, and cycle 6 (each cycle is 28 days) The MDASI-BT consists of 23 symptoms rated on an 11 point scale (0 - did not interfere, to 10 - interfered completely) to indicate the symptoms that interfere with a participants life in the last 24 hours. All participants with at least one valid questionnaire are included in the analyses. We calculated the mean core symptom interference score rated on the scale from 0- did not interfere, to 10- interfered completely at the time of clinical evaluation. Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom interference measures. For example, an increase of 2 points or more would mean a moderate improvement, whereas a decrease of 2 points or more would be interpreted as moderate worsening.
Mean Symptom Interference With Daily Activities Using the MD Anderson Symptom Inventory for Spine Tumors (MDASI-SP) Instrument Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 2, cycle 4, and cycle 6 (each cycle is 28 days) The MDASI-SP consists of 23 symptoms rated on an 11 point scale (0 - did not interfere, to 10 - interfered completely) to indicate the symptoms that interfere with a participants life in the last 24 hours. All participants with at least one valid questionnaire are included in the analyses. We calculated the mean core symptom interference score rated on the scale from 0- did not interfere, to 10- interfered completely at the time of clinical evaluation. Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom interference measures. For example, an increase of 2 points or more would mean a moderate improvement, whereas a decrease of 2 points or more would be interpreted as moderate worsening.
Trial Locations
- Locations (2)
Massachusetts General Hospital/Dana Farber
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States