Phase II Trial of Carboplatin and Bevacizumab for the Treatment of Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma in Adults
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
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
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
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).