Carboplatin and Bevacizumab for Recurrent Ependymoma
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Carboplatin and Bevacizumab for the Treatment of Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma in Adults: A Multi-Center Trial|
- progression-free survival (PFS) at one year [ Time Frame: one year after end of treatment ] [ Designated as safety issue: No ]
- To evaluate response rates to this chemotherapy. [ Time Frame: end of treatment ] [ Designated as safety issue: No ]
- To evaluate overall survival in this population. [ Time Frame: time of death ] [ Designated as safety issue: Yes ]
- To evaluate toxicity profile of this combination. [ Time Frame: completion of study ] [ Designated as safety issue: No ]
- To evaluate the occurrence of symptoms and correlate to disease progression and tolerance to treatment using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT or MDASI-SP) selfreporting tool. [ Time Frame: completion of study ] [ Designated as safety issue: No ]
|Study Start Date:||October 2015|
|Estimated Study Completion Date:||July 2020|
|Estimated Primary Completion Date:||July 2018 (Final data collection date for primary outcome measure)|
The total duration of treatment will be 6 cycles. After cycle 6, carboplatin should be discontinued, but bevacizubab may be continued at the descretion of the treating physician.
Carboplatin will be given on day 1 of each cycle; the carboplatin dose should be calculated using the Calvert formula: Carboplatin dose (mg) = target AUC x (CrCl + 25; 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 physicianDrug: Bevacizumab
Bevacizumab will be administered on days 1 and 15 of each cycle. Bevacizumab will be administered at a dose of 10 mg/kg; 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.
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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 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 GBMs.
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.
- Histologically proven intra-cranial or spinal ependymoma or anaplastic ependymoma. There must be pathologic or imaging confirmation of tumor progression or regrowth.
- Patients must be greater than or equal to18 years old.
- Patients must have a Karnofsky performance status of greater than or equal to 60.
- Patients must have adequate bone marrow function, adequate liver function and adequate renal function before starting therapy.
- Patients must have recovered from the toxic effects of prior therapy.
- Patients having undergone recent resection of recurrent or progressive tumor will be eligible.
- Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 42 days from the completion of radiation therapy to study entry.
- Women of childbearing potential must have a negative B-HCG pregnancy test documented within 14 days prior to registration.
- Women of childbearing potential and male participants agree to practice adequate contraception.
- Patients must not have any significant medical illnesses or active infection.
- Patients must not have history of any other cancer.
- Patients must not be pregnant/breast feeding.
- Patients must not have received prior therapy with bevacizumab, or related drugs.
- No active bleeding or pathological condition that carries a high risk of bleeding.
- No major surgical procedure, open biopsy, or significant traumatic injury within 28 days.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01295944
|Contact: Christine M Bryla, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|United States, Massachusetts|
|Harvard Cancer Center||Recruiting|
|Boston, Massachusetts, United States, 02114|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10021|
|United States, Texas|
|MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030-4096|
|Principal Investigator:||Mark R Gilbert, M.D.||National Cancer Institute (NCI)|