- - Patients must have histologically confirmed glioblastoma or gliosarcoma.
- - Patients must have evidence for tumor progression by magnetic resonance imaging
(MRI) or computed tomography (CT) scan.
This scan should be performed within 14 days
prior to registration and on a fixed dose of steroids for at least 5 days. If the
steroid dose is increased between the date of imaging and registration a new
baseline MR/CT is required. The same type of scan, ie, MRI or CT must be used
throughout the period of protocol treatment for tumor measurement.
- - Patients must have progressed after radiation therapy and must have an interval of
greater.
- - Patients must have recovered from the toxic effects of prior therapy: 4 weeks from
any investigational agent, 4 weeks from prior cytotoxic therapy, two weeks from
vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration,
and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide,
cis-retinoic acid, etc. Any questions related to the definition of non-cytotoxic
agents should be directed to the Study Chair.
All toxicities from prior therapies
should be resolved to National Cancer Institute (NCI) Common Terminology Criteria
for Adverse Events (CTCAE) less than or equal to grade 1 (except for toxicities such
as alopecia or vitiligo).
- - Patients must be > 18 years old.
Because no dosing or adverse event data are
currently available on the use of TRC105 in patients < 18 years of age, children are
excluded from this study, but will be eligible for future pediatric trials.
- - Karnofsky performance status > 60%
- Life expectancy of greater than 12 weeks.
- - Patients must have normal organ and marrow function as defined below:
- leukocytes > 3,000/microliter.
- - absolute neutrophil count > 1,500/microliter.
- - platelets > 100,000/microliter.
- - total bilirubin < 1.5 times ULN institutional upper limit of normal.
- - Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase
(SGOT)/alanine aminotransaminase (ALT) serum glutamic pyruvic transaminase
(SGPT) < 2.5 times institutional upper limit of normal.
- - Prothrombin time (PT)/Partial thromboplastin time (PTT) < 1.5 times
institutional upper limit of normal.
- - creatinine < 1.5 times ULN within normal institutional limits.
OR.--creatinine clearance > 60 glomerular filtration rate for patients with creatinine.levels above institutional normal.
- - hemoglobin of > 9grams/deciliter without transfusion support in the past 28 days.
- - Patients must not have any significant medical illnesses that, in the
investigators opinion, cannot be adequately controlled with appropriate therapy
or would compromise the patients ability to tolerate this therapy.
- - 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.
- - They should have residual disease following resection of recurrent tumor.
To best assess the extent of residual disease post-operatively, a computed tomography
(CT)/ magnetic resonance imaging (MRI) should be done:
no later than 96 hours in the immediate post-operative period and.
- - at least 4 weeks post-operatively, and.
- - within 14 days of registration, and.
- - on a steroid dosage that has been stable for at least 5 days.
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.
- - The effects of TRC105 on the developing human fetus are unknown.
For this reason and
because antiangiogenic agents are known to be teratogenic, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry and for the duration of
study participation. Should a woman become pregnant or suspect she is pregnant while
she or her partner is participating in this study, she should inform her treating
physician immediately. Men treated or enrolled on this protocol must also agree to
use adequate contraception prior to the study, for the duration of study
participation, and 4 months after completion of TRC105 administration.
- - Patients must have the ability to understand and the willingness to sign a written
informed consent document.
- - A baseline 12 lead electrocardiogram (ECG) to be performed within 2 weeks of trial.
EXCLUSION CRITERIA.
- - Patients who are receiving any other investigational agents and/or who have received
an investigational agent in the prior 28 days.
- - Patients may not have had prior therapy with vascular endothelial growth factor
(VEGF) receptor inhibitors.
- - Patients with a history of peptic ulcer disease or erosive gastritis within the past
6 months, unless treated for the condition and complete resolution has been
documented by esophagogastroduodenoscopy (EGD).
- - History of allergic reactions attributed to compounds of similar chemical or
biologic composition to TRC105.
- - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance
with study requirements.
- - Exclude patients who have had angina, MI, symptomatic congestive heart failure
(CHF), cerebral vascular accident (CVA), transient ischemic attack (TIA),
arterial embolism, pulmonary embolism, deep vein thrombosis (DVT), percutaneous
transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG)
within the last 6 months.
- - Exclude patients with cardiac arrhythmias > grade 2 in the last 28 days.
- - Exclude patients with chronic hypertension, systolic BP > 140 and/or diastolic
BP > 90 despite optimal treatment.
- - Exclude human immunodeficiency virus (HIV)+ patients who have CD4 counts which
are below the lower limit of normal for the institution.
- - Patients known to have a malignancy (other than their glioblastoma) that has
required treatment in the last 12 months and/or is expected to require treatment in
the next 12 months (except non-melanoma skin cancer or carcinoma in-situ in the
cervix)
- Patients are not allowed to receive concurrent anti-coagulation, and may not have
received thrombolytic or anticoagulant agents (except heparin or alteplase to
maintain intravenous (IV) catheters) within 10 days prior to drug administration.
- - Serious or non-healing wound, ulcer or bone fracture.
- - History of abdominal fistula, gastrointestinal perforation or intra-abdominal
abscess within 6 months.
- - Evidence of bleeding diathesis or coagulopathy.
- - Patients with a history of hereditary hemorrhagic telangiectasia (HHT)
- Pregnant women are excluded from this study because TRC105 and antiangiogenic agents
with the potential for teratogenic or abortifacient effects.
Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with TRC105, breastfeeding should be discontinued if the
mother is treated with TRC105.
