Carboplatin and Bevacizumab for Recurrent Ependymoma
|First Submitted Date ICMJE||February 11, 2011|
|First Posted Date ICMJE||February 15, 2011|
|Last Update Posted Date||November 23, 2017|
|Start Date ICMJE||October 21, 2015|
|Estimated Primary Completion Date||July 1, 2018 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||progression-free survival (PFS) at one year [ Time Frame: one year after end of treatment ]|
|Original Primary Outcome Measures ICMJE
||Number of Participants with Progression-Free Survival at 1 Year [ Time Frame: 1 year following treatment ]
Progression-Free Survival (PFS) defined as length of time during and after treatment in which a patient is living with a disease that does not get worse.
|Change History||Complete list of historical versions of study NCT01295944 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Carboplatin and Bevacizumab for Recurrent Ependymoma|
|Official Title ICMJE||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|
|Brief Summary||The goal of this clinical research study is to learn if the combination of bevacizumab and carboplatin can help to control recurrent pendymoma. The safety of this drug combination will also be studied....|
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.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms||Experimental: 1
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.
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||35|
|Estimated Completion Date||July 1, 2020|
|Estimated Primary Completion Date||July 1, 2018 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Histologically proven intra-cranial or spinal ependymoma or anaplastic ependymoma. There must be pathologic or imaging confirmation of tumor progression or regrowth.
The patient must have at least 1 block of tissue or 15 unstained slides at a minimum available for central pathology review and molecular profiling of the tissue sample.
All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information.
Patients must be > 18 years old.
Patients must have a Karnofsky performance status of > 60.
Patients must have adequate bone marrow function (WBC > 3,000/microliter, ANC > 1,500/mm^3, platelet count of > 100,000/mm^3, and hemoglobin > 10 gm/dl), adequate liver function (SGOT [AST <92.5 Units/L] and bilirubin < 1.5 mg/dL), and adequate renal function (creatinine < 1.5 mg/dL and calculated creatinine clearance > 60 cc/min) before starting therapy. Eligibility level for hemoglobin may be reached by transfusion.
Patients must have shown unequivocal radiographic evidence for tumor progression by MRI or CT scan.
At the time of registration: Patients must have recovered from the toxic effects of prior therapy: > 28 days from any investigational agent, >28 days from prior cytotoxic therapy, >14 days from vincristine, >42 days from nitrosoureas, >21 days from procarbazine administration, and >7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Principal Investigator.
Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
They have recovered from the effects of surgery.
A minimum of 28 days have elapsed from the day of surgery to the day of registration Step 2.
For core or needle biopsy, a minimum of 7 days must have elapsed prior to registration Step 2.
Residual disease following resection of recurrent ependymoma is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/ MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, within 14 days prior to consent. If the within 96-hour after surgery scan is more than 14 days before consent the scan needs to be repeated. If the steroid dose is increased between the date of imaging and consent, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.
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. Note: Patients with an indication for craniospinal radiotherapy (i.e., extensive leptomeningeal disease) but have refused palliative craniospinal radiotherapy are eligible.
Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, MR spectroscopy, or surgical/pathological documentation of disease.
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
Patients withany significant medical illnesses that in the investigator s opinion cannot be adequately controlled with appropriate therapy or would compromise the patient s ability to tolerate this therapy.
Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma insitu of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
Patients with an active infection or serious intercurrent medical illness.
Patients found to be pregnant/breast feeding. Patients must not be pregnant because animal studies show that carboplatin and bevacizumab are teratogenic
Patients with any disease that will obscure toxicity or dangerously alter drug
Patients who have received prior therapy with bevacizumab, or related drugs (previous therapy with carboplatin is allowed).
Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg) despite antihypertensive medication.
New York Heart Association (NYHA) Grade II or greater congestive heart failure.
9 History of myocardial infarction or unstable angina within 12 months prior to Day 1.
History of stroke or transient ischemic attack.
Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1.
History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1.
Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). (To be eligible, Prothrombin time/international normalized ratio (PT INR) should be < 1.4 for patients not on warfarin.)
Patients receiving full-dose anticoagulants therapy (e.g., warfarin or LMW heparin) and does not meet both of the following criteria:
No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin.
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of treatment or anticipation of need for major surgical procedure during the course of the study.
Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1.
History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1.
Serious, non-healing wound, active ulcer, or untreated bone fracture.
Proteinuria as demonstrated by a UPC ratio greater than or equal to 1.0 at screening, or Urine dipstick for proteinuria greater than or equal to 2+ (patients discovered to have greater than or equal to 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate less than or equal to 1g of protein in 24 hours to be eligible).
Known hypersensitivity to any component of bevacizumab.
Patients has current active hepatic or biliary disease (with exception of patients with Gilbert s syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).
|Ages||18 Years to 99 Years (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01295944|
|Other Study ID Numbers ICMJE||160009
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )|
|Study Sponsor ICMJE||National Cancer Institute (NCI)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||November 16, 2017|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP