LBH589 and Bevacizumab in Patients With Recurrent High Grade Glioma
Status: Recruiting
Phase: Phase 1/Phase 2
Diagnosis: Brain/Neuro Cancer: Other Non-Glioblastoma, Brain/Neuro Cancer: Recurrent Glioblastoma
NCT ID: NCT00859222
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 08-342
The purpose of this research study is to determine the amount of LBH589 that can be given to people safely when LBH589 is given in combination with bevacizumab. LBH589 in combination with bevacizumab is a drug combination that may stop cancer cells from growing abnormally. LBH589 has been used alone in other trials for solid tumor malignancies. Bevacizumab is FDA approved for use in patients with colorectal cancer and has been studied extensively in other types of solid tumors. The combination of LBH589 and bevacizumab has no yet been studied but information from other studies suggests that the combination may help prevent the growth of the participant's tumor.
Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital, Beth-Israel Deaconess Medical Center
Overall PI:
Patrick Wen, MD,
Dana-Farber Cancer Institute
Site-responsible Investigators:
Andrew Chi, MD, PhD,
Massachusetts General Hospital
Contacts:
Dana-Farber Cancer Institute:
Samantha Hammond, 617-632-5396,
samantha_hammond@dfci.harvard.edu
Massachusetts General Hospital:
Cancer Trials Call Center, 877-789-6100
Eligibility Criteria
Inclusion Criteria:
- 18 years of age or older
- Karnofsky Performance Status 60 or greater
- Life expectancy of at least 8 weeks
- Histologic diagnosis of GBM, gliosarcoma, anaplastic astrocytoma (AA), anaplastic
oligodendroglioma (AO), or anaplastic mixed oligoastrocytoma (AMO)
- Unequivocal progression by magnetic resonance imaging (MRI) or computed tomography
(CT) scan. A scan must be performed within 14 days prior to registration and on a
steroid dose that has been stable for at least 5 days. The same type of scan must be
used throughout the period of protocol treatment for tumor measurement. Subjects with
recurrence who undergo resection and are left without measurable or evaluable disease
are eligible.
- Patients must have failed prior radiation therapy and must have an interval of greater
than or equal to 60 days from the completion of radiation therapy to study entry.
- Patients must have recovered from the toxic effects of prior therapy. Residual
toxicity from any previous treatment must be Grade 1 or less.
- Sufficient time for recovery from prior therapy: 28 days from any investigational
agent, 28 days from prior cytotoxic therapy, and 7 days for non-cytotoxic agents.
- Patients with prior therapy that included interstitial brachytherapy or stereotactic
radiosurgery must have confirmation of true progressive disease rather than radiation
necrosis based upon positron emission tomography (PET), Thallium scanning, MR
spectroscopy or surgical documentation of disease.
- Subjects who have undergone recent resection of recurrent or progressive tumor will be
eligible as long as all of the following conditions apply:
a) prior to initiating therapy, 4 weeks must have elapsed since surgery b) residual
disease following resection of recurrent malignant glioma is not mandated for
eligibility. To assess the extent of residual disease postoperatively, a MRI or CT
should be done at least 4 weeks postoperatively and within 14 days prior to
registration.
- Clinical laboratory tests within 14 days prior to enrollment meeting the criteria
listed in the protocol
- Cardiology assessment: Baseline MUGA or Echocardiogram must demonstrate LVEF 50% or
greater
- Electrocardiogram: 3 sequential ECGs separated by at least 5 minutes. Each individual
pretreatment QTc interval must be 460 msec or less and the average of the QTc
intervals must be 450 msec or less.
- Patients in non-hypertensive or has well-controlled hypertension (systolic blood
pressure of < 140mm Hg or diastolic pressure < 90 mm Hg).
- Female subjects of childbearing potential must have a negative pregnancy test
confirmed within 48 hours prior to dosing with the study drug
- Subjects must be free of any clinically relevant disease (other than recurrent GBM or
gliosarcoma) that would, in the Investigator's opinion, interfere with the conduct of
the study or study evaluations.
PHASE I Inclusion Criteria (the following modifications to the general eligibility criteria
apply to Phase I patients only):
- Patients may have been treated for any number of prior relapses. Relapse is defined
as progression following initial therapy
- Patients must be willing to participate in the pharmacokinetic studies
PHASE II Inclusion Criteria (phase II patients must meet the general eligibility criteria
as well as the following):
- Patients may have had treatment for no more than 2 prior relapses.
- It is mandatory that 15 unstained paraffin slides or 1 representative tissue block be
available from original surgery or definitive surgery or the surgery closest to
initiation of this clinical trial.
Exclusion Criteria:
- Subject has received previous therapy with anti-VEGF targeted agents or with any
histone deacetylase inhibitors. Prior treatment with valproic acid for seizures is
allowed but requires a washout of at least 14 days prior to starting LBH589.
- Bleeding diathesis or coagulopathy
- History of intratumoral or peritumoral hemorrhage if deemed significant by the
treating physician
- Treatment with warfarin. For patients requiring anticoagulation therapy, only
therapeutic low molecular weight heparin or factor Xa inhibitors are permitted.
- Patients who have received any investigational drug or undergone major surgery < 4
weeks prior to starting study drug or who have not recovered from side effects of such
therapy
- 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 any disease that will obscure toxicity or dangerously alter drug
metabolism
- 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 has not received
treatment for that particular disease for a minimum of 3 years
- Impaired cardiac function as described in the protocol
- Uncontrolled hypertension and/or prior history of hypertensive crisis or hypertensive
encephalopathy
- Significant vascular disease within 6 months prior to Day 1
- History of stroke or transient ischemic attack within 6 months prior to Day 1
- Patients with unresolved diarrhea > CTCAE grade 1
- Patients with INR > 1.5
- Patients with major surgery or a significant traumatic injury within 28 days prior to
Day 1
- Patients with any condition that impairs their ability to swallow and/or absorb pills
- Concomitant use of drugs with a risk of causing torsades de pointes
- Concomitant use of CYP3A4 inhibitors during the treatment phase of the study and
within 72 hours prior to starting treatment
- Concomitant use of any anti-cancer therapy or radiation therapy, or any other
investigational agent
- Patients has known human immunodeficiency virus (HIV) of hepatitis C infection,
baseline treating for HIV or hepatitis C is not required
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to LBH589 or bevacizumab, or their excipients
- Patient is in a situation or condition that, in the opinion of the investigator, may
interfere with optimal participation in the study
- Patient has a significant history of non-compliance to medical regimens
- 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 ration of 1.0 or greater at screening
- Subject is pregnant or intends to become pregnant during the study