Carboplatin and Bevacizumab for Recurrent Ependymoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
CERN Foundation - Collaborative Ependymoma Research Network
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01295944
First received: February 11, 2011
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Brain Tumor
Spinal Tumor
Glial Tumour of Brain
Ependymal Tumour of Brain
Spinal Cord Ependymoma
Anaplastic Ependymoma
Drug: Bevacizumab
Drug: Carboplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 46
Study Start Date: March 2011
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab + Carboplatin
Bevacizumab 10 mg/kg by vein on days 1 and 15 of each 28 day cycle. Carboplatin AUC=5 mg/mL/min by vein on day 1 of each 28 day cycle.
Drug: Bevacizumab
10 mg/kg by vein on days 1 and 15 of each 28 day cycle.
Other Names:
  • Avastin
  • Anti-VEGF Monoclonal Antibody
  • rhuMAb-VEGF
Drug: Carboplatin
AUC=5 mg/mL/min by vein on day 1 of each 28 day cycle.
Other Name: Paraplatin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically proven intra-cranial or spinal ependymoma or anaplastic ependymoma. There must be pathologic or imaging confirmation of tumor progression or regrowth. The patient's histologic diagnosis must be confirmed on Central Pathology Review prior to registration Step 2. * If a patient has already had central pathology review at MDACC (for example, from a previous enrollment to protocol CERN08-02), the central pathology does not need to be repeated. Previous pathology confirmation can be utilized for this study's pathology eligibility testing.
  2. 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.
  3. 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 registered in the MDACC OMCR database prior to treatment with study drug.
  4. Patients must be >/= 18 years old.
  5. Patients must have a Karnofsky performance status of >/= 60.
  6. Patients must have adequate bone marrow function (WBC >/= 3,000/µl, ANC >/= 1,500/mm3, platelet count of >/= 100,000/mm3, 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. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
  7. Patients must have shown unequivocal radiographic evidence for tumor progression by MRI or CT scan. If an MRI is being obtained to verify eligibility, it is recommended that the MRI parameters follow the specifications detailed in the protocol so that the patient will not require a repeat MRI prior to treatment start.
  8. 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 Study Chair.
  9. Patients having undergone recent resection of recurrent or progressive tumor will be eligible with the following conditions apply: a) They have recovered from the effects of surgery. b) 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. c) 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 registration. If the within 96-hour after surgery scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.
  10. 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.
  11. 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.
  12. Women of childbearing potential must have a negative B-HCG pregnancy test documented within 14 days prior to registration.
  13. Women of childbearing potential and male participants agree to practice adequate contraception.

Exclusion Criteria:

  1. 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.
  2. Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
  3. Patients must not have active infection or serious intercurrent medical illness.
  4. Patients must not be pregnant/breast feeding. Patients must not be pregnant because animal studies show that carboplatin and bevacizumab are teratogenic.
  5. Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
  6. Patients must not have received prior therapy with bevacizumab, or other agents known to target the Vascular Endothelial Growth Factor (VEGF) pathway including sorafenib, sunitinib, or cediranib.
  7. Inadequately controlled hypertension (defined as systolic blood pressure >140 mmHg and/or diastolic blood pressure > 90 mmHg) despite antihypertensive medication.
  8. 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.
  10. History of stroke or transient ischemic attack.
  11. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1.
  12. History of hemoptysis (>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1.
  13. 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: a) No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices); b) 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.
  14. 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.
  15. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1.
  16. History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1.
  17. Serious, non-healing wound, active ulcer, or untreated bone fracture.
  18. Proteinuria as demonstrated by a UPC ratio >/= 1.0 at screening, or Urine dipstick for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate </= 1g of protein in 24 hours to be eligible).
  19. Known hypersensitivity to any component of bevacizumab.
  20. 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01295944

Contacts
Contact: Mark R. Gilbert, MD,BS 713-792-2883

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Elizabeth R. Gerstner, M.D.         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Principal Investigator: Martin Fleisher, M.D.         
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Mark R. Gilbert, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
CERN Foundation - Collaborative Ependymoma Research Network
Investigators
Principal Investigator: Mark R. Gilbert, MD,BS UT MD Anderson Cancer Center
Study Chair: Antonio Omuro, MD Memorial Sloan-Kettering Cancer, CERN Lead Site
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01295944     History of Changes
Other Study ID Numbers: CERN09-02, NCI-2011-01283
Study First Received: February 11, 2011
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Recurrent Ependymoma
Spinal cord ependymoma
Anaplastic ependymoma
Brain tumor
Spinal cord tumor
Carboplatin
Paraplatin
cancer

Additional relevant MeSH terms:
Brain Neoplasms
Ependymoma
Glioma
Spinal Cord Neoplasms
Spinal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Spinal Cord Diseases
Bone Neoplasms
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Antibodies, Monoclonal
Bevacizumab
Carboplatin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 28, 2014