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Carboplatin and Bevacizumab for Recurrent Ependymoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01295944
First received: February 11, 2011
Last updated: September 21, 2016
Last verified: September 2016

February 11, 2011
September 21, 2016
October 2015
July 2018   (final data collection date for primary outcome measure)
progression-free survival (PFS) at one year [ Time Frame: one year after end of treatment ] [ Designated as safety issue: No ]
Number of Participants with Progression-Free Survival at 1 Year [ Time Frame: 1 year following treatment ] [ Designated as safety issue: No ]
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.
Complete list of historical versions of study NCT01295944 on ClinicalTrials.gov Archive Site
  • 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 ]
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Carboplatin and Bevacizumab for Recurrent Ependymoma
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
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....

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 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.

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.

Eligibility:

  • 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.

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.
Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Ependymoma
  • Anaplastic Ependymoma
  • Drug: Carboplatin
    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 physician
  • Drug: 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.
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.
Interventions:
  • Drug: Carboplatin
  • Drug: Bevacizumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
46
July 2020
July 2018   (final data collection date for primary outcome measure)
  • INCLUSION CRITERIA:

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

contraception.

EXCLUSION CRITERIA:

Patients must not have any 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 must not have active infection or serious intercurrent medical illness.

Patients must not be pregnant/breast feeding. Patients must not be pregnant because animal studies show that carboplatin and bevacizumab are teratogenic

Patients must not have any disease that will obscure toxicity or dangerously alter drug

metabolism.

Patients must not 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 on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria to be eligible:

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 must not have current active hepatic or biliary disease (with exception of patients with Gilbert s syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).

Both
18 Years to 99 Years   (Adult, Senior)
No
Contact: Christine M Bryla, R.N. (301) 451-7868 christina.bryla@nih.gov
United States
 
NCT01295944
160009, 16-C-0009
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National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Mark R Gilbert, M.D. National Cancer Institute (NCI)
National Institutes of Health Clinical Center (CC)
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP