Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Carboplatin and Bevacizumab for Recurrent Ependymoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 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: July 30, 2014
Last verified: July 2014

February 11, 2011
July 30, 2014
March 2011
March 2016   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01295944 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
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

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.

The Study Drugs:

Carboplatin is designed to interfere with the growth of cancer cells by stopping cell division, which may cause the cells to die.

Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive carboplatin by vein over 30 minutes on Day 1 of each 28-day cycle. You will receive bevacizumab by vein over 90 minutes on Days 1 and 15 of each cycle.

Study Visits:

Every week:

-Blood (about 1 - 2 teaspoons) will be drawn for routine tests.

Every 4 weeks:

  • Urine will be collected to check your kidney function.
  • You will be asked about any drugs you may be taking and if you have had any side effects.

Every 8 weeks:

  • Your medical history will be recorded.
  • You will have a physical exam, including measurement of your vital signs.
  • You will have a neurological exam.
  • Your performance status will be recorded.
  • You will complete the quality of life questionnaire.
  • You will have an MRI scan or CT scan of the head and/or spine to check the status of the disease.

At any time during the study, extra tests may be performed if the doctor thinks they are needed for your safety. The study doctor will tell you more about any extra tests.

Length of Study:

You will receive up to 6 cycles of the study drug combination. You will be taken off study early if the disease gets worse or you experience intolerable side effects.

If the disease has not gotten worse after 6 cycles of receiving the study drug combination, you will be able to continue receiving bevacizumab alone for as long as the doctor thinks it is in your best interest. You will continue to follow the same study visit schedule detailed above.

Long-Term Follow-up:

If you go off study because the disease got worse or you experienced intolerable side effects, the study staff will call you every 3 months from then on to check your health. Each phone call should take about 5 minutes.

This is an investigational study. Carboplatin is FDA approved and commercially available for the treatment of advanced ovarian cancer. Bevacizumab is FDA approved and commercially available for the treatment of glioblastoma multiforme (a type of brain tumor). The use of these drugs in combination in ependymoma is investigational.

Up to 46 patients will take part in this study. Up to 25 patients will be enrolled at MD Anderson.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Brain Tumor
  • Spinal Tumor
  • Glial Tumour of Brain
  • Ependymal Tumour of Brain
  • Spinal Cord Ependymoma
  • Anaplastic Ependymoma
  • 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
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.
Interventions:
  • Drug: Bevacizumab
  • Drug: Carboplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
46
Not Provided
March 2016   (final data collection date for primary outcome measure)

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 step 2 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 step 2 registration. If the within 96-hour after surgery scan is more than 14 days before step 2 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).
Both
18 Years and older
No
Contact: Mark R. Gilbert, MD,BS 713-792-2883
United States
 
NCT01295944
CERN09-02, NCI-2011-01283
No
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
CERN Foundation - Collaborative Ependymoma Research Network
Principal Investigator: Mark R. Gilbert, MD,BS UT MD Anderson Cancer Center
Study Chair: Antonio Omuro, MD Memorial Sloan-Kettering Cancer, CERN Lead Site
M.D. Anderson Cancer Center
July 2014

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