Avastin and Temozolomide Following Radiation and Chemotherapy for Newly Diagnosed Glioblastoma Multiforme: A Phase II Study
18 Years
N/A
Both
Glioblastoma Multiforme
Trial Information
Avastin and Temozolomide Following Radiation and Chemotherapy for Newly Diagnosed Glioblastoma Multiforme: A Phase II Study
The study consists of the following: 1) a screening period of up to 28 days; 2) a treatment
period of radiation with daily temozolomide that lasts approximately 6 weeks, 3) a study
treatment period that will last until either your tumor grows or you experience unacceptable
side effects; and 4) a 30-day follow-up period after treatment has ended. Additionally,
basic information concerning your condition will be collected every 2 months after the
follow-up period for the rest of your life.
During this study, Dr. Nicholas and his research team will collect information about you for
the purposes of this research. This includes name, address, dates (i.e., date of birth,
date of consent), telephone number, and medical record number. Slides of your tumor tissue
that were used to diagnose your GBM will be sent to a pathologist to confirm the diagnosis
of GBM. After this review has been completed your slides will be returned to the hospital
that provided them. Preserved samples of your tumor will also be sent for a test to
determine how effective the temozolomide might be in your case. Any remaining tissue will
be returned to the hospital that provided it.
Screening phase (following diagnosis of GBM at surgery) To determine if you are eligible to
participate in this study, you will undergo a screening process that will involve the
following
- Assessment of your cancer by magnetic resonance imaging (MRI) of your brain using an
intravenous (in your vein) contrast material
- Recording of your general medical, surgical and cancer history
- Physical examination, including measurement of your blood pressure, height and weight
- Evaluation of your performance status (your ability to carry on daily activities)
- Neurologic examination (how well your nerves and muscles work)
- Blood sample for laboratory tests (approximately 2 to 3 tablespoons) to evaluate your
blood counts, liver, and kidney function
- Serum pregnancy test if you are a woman of childbearing potential
- Urine sample
- Recording of any medications taken within the past 14 days
Radiation and daily temozolomide chemotherapy You will begin radiation treatment within 5
weeks of surgery. You will take temozolomide orally once daily (seven days a week) during
radiation treatments (which occur Monday - Friday and last approximately six weeks). You
will take a medication to prevent a rare form of pneumonia (pneumocystis carinii) that can
occur when temozolomide is given on a daily basis. That may be either in pill form or
inhaled. During radiation treatment you will be seen every two weeks by a study doctor at
which time you will be asked how you are tolerating the treatment. A physical examination,
(including neurological evaluation), will be performed. Blood tests (1-2 tablespoons) will
be performed to assure that you are not having any side-effects from the chemotherapy.
Post-radiation treatment Two to four weeks after completing radiation you will have a brain
MRI scan. Beginning four weeks after radiation ends, the study drug and temozolomide will
begin. The study drug (Avastin) will be administered by IV infusion (through a vein) every 2
weeks. Temozolomide will be taken orally for five consecutive days of every 28 days. In
other words, you will receive two intravenous infusions of Avastin and five days of
temozolomide every 28 days. This constitutes a treatment cycle. These cycles will continue
indefinitely. The dose of Avastin will be based upon your weight during screening and will
remain the same throughout the study. The temozolomide dose during radiation will be based
on your height and weight at screening. During the study phase, temozolomide will be dosed
according to your height and weight at the beginning of each treatment cycle. The dose may
be delayed for up to four weeks if your blood counts are low. If temozolomide still cannot
be given because your blood counts are low for longer than four weeks, the temozolomide will
be stopped but the Avastin may still be continued.
Your first dose of Avastin will be given as over 90 minutes. If you tolerate the 90 minute
infusion well, infusions in the future may be given over a shorter period of time. However,
if you do not tolerate the shorter infusion time, future infusions will be given over the
longer period that you previously tolerated. If you experience any problems during or
following the infusion, you will be monitored by trained staff until it is considered safe
for you to leave.
The dose of Avastin that you receive may be stopped or slowed based on how well you tolerate
the treatment. If you must stop treatment because of unfavorable side effects, you may be
able to restart treatment once the side effect has improved or resolved. Your doctor will
discuss with you whether it is in your best interest to continue treatment. If you stop
study drug treatment, you should continue to return to be evaluated as explained below.
Temozolomide will be taken at bedtime on an empty stomach (at least 2 hours after any meal).
Prior to each dose of temozolomide, you will take an anti-nausea pill (ondansetron,
granisetron, or dolasetron) to reduce nausea and vomiting.
The treatment cycles described above will continue until: 1) your tumor grows, 2) you have
unacceptable side effects, 3) you choose to withdraw from this research study, or 4) your
participation is ended by Dr. Nicholas or Genentech.
During the first treatment day of each 28 day cycle you will receive Avastin. Your blood
pressure will be monitored, and you will have a physical examination, a neurologic
examination, and an evaluation of your performance status (how well you are functioning in
daily activities). On the same day, you will begin temozolomide chemotherapy. You will have
a blood sample drawn for laboratory tests (approximately 2-3 tablespoons), and a urine
sample taken. You will be asked by the study doctor about any health problems you have and
medications you take. Additional blood samples may be drawn at the discretion of your
doctor as part of your standard care.
On day 14 of every treatment cycle you will return to the clinic to receive an infusion of
Avastin. At that time, your blood pressure will be taken, and you will have a physical
examination and an evaluation of your performance status. On day 21 of each cycle you will
have blood work (1-2 tablespoons) to see how well you are tolerating the treatment. Every 8
weeks (after every 2 cycles immediately prior to your next cycle) you will have an MRI of
your brain to determine measurements of your tumor.
Inclusion Criteria:
1. Disease-Specific Concerns Histologically confirmed GBM as determined by central
pathology review Supratentorial location
2. General Medical Concerns 18 years of age; Karnofsky performance status > 60;
Tumor-related contrast enhancement on initial and post-operative Gd-MRI; Recovery
from effects of surgery and/or its complications prior to initiating radiotherapy;
Radiotherapy must begin < 5 weeks following surgery; Pre-and post-operative Gd-MRI
prior to the initiation of radiotherapy; Adequate hematological, renal, and hepatic
function:hemoglobin > 10 grams hematocrit > 30%, platelets > 100,000 per mm3, BUN <
25 mg/dl, Creatinine < 1.5 mg/dl, Total bilirubin < 1.5 mg/dl, SGOT or SGPT < twice
institutional normal range, Subjects must not be pregnant or nursing, Use of
effective means of contraception (men and women) in subjects of child-bearing (women)
and at all ages (men), Study-specific signed informed consent, Ability to comply with
study follow-up procedures.
-
Exclusion Criteria:
- a. Disease-Specific Concerns: malignant gliomas graded less than GBM; infratentorial
tumor location; recurrent disease; intra-tumoral hemorrhage; Placement of Gliadel®
wafers; b. Bevacizumab-Specific Concerns: Inadequately controlled hypertension
(defined as systolic blood pressure 150 and/or diastolic blood pressure > 100 mmHg on
antihypertensive medications); Any prior history of hypertensive crisis or
hypertensive encephalopathy; History of myocardial infarction or unstable angina
within 6 months prior to study enrollment; History of stroke or transient ischemic
attack within 6 months prior to study enrollment; New York Heart Association (NYHA)
Grade II or greater CHF (see Appendix E); Significant vascular disease (e.g., aortic
aneurysm, aortic dissection); Symptomatic peripheral vascular disease; Evidence of
bleeding diathesis or coagulopathy; History of abdominal fistula, gastrointestinal
perforation, or intra-abdominal abscess within 6 months prior to study enrollment;
History of intracerebral abscess within 6 months prior to study enrollment; Major
surgical procedure, open biopsy, or significant traumatic injury within 28 days prior
to study enrollment (exclusive of craniotomy); anticipation of need for major
surgical procedure during the course of the study; Core biopsy or other minor
surgical procedure, excluding placement of a vascular access device, within 7 days
prior to study enrollment; Serious non-healing wound, ulcer, or bone fracture;
Proteinuria at screening as demonstrated by either; Urine protein:creatinine (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);
Known hypersensitivity to any component of Avastin. c. General Medical Exclusions
Subjects meeting any of the following criteria are ineligible for study entry:
Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than a Genentech-sponsored Avastin
cancer study; History of any other malignancy within 5 years (except non-melanoma skin
cancer or carcinoma in situ of the cervix);Pregnant or nursing females; Unstable systemic
disease, including active infection, uncontrolled hypertension, or serious cardiac
arrhythmias requiring medication;
Screening clinical laboratory values:
Absolute neutrophil count < 1500/ul, Platelet count < 100,000/ul, Total bilirubin > 1.6
mg.dl, AST/ALT > 1.5 x the upper limit of normal ( ULN), Creatinine > 1.2 x ULN, Urine
protein/creatinine ratio > 1.0, International normalized ration (INR) > 1.5 and activated
partial thromboplastin time (aPTT) > 1.5 x ULN (except for subjects receiving
anticoagulation therapy) in the absence of therapeutic intent to anticoagulate the
subject. Therapeutic anticoagulation is permitted.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Determine estimates of the objective response and PFS in subjects wtih newly diagnosed GBM who are treated with radiotherapy and daily temozolomide/monthly cycles of temozolomide and Avastin until either disease progression or unacceptable toxicities
Outcome Time Frame:
every 8 weeks
Safety Issue:
No
Principal Investigator
Martin Kelly Nicholas, MD PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Chicago
Authority:
United States: Food and Drug Administration
Study ID:
15149A
NCT ID:
NCT00590681
Start Date:
February 2007
Completion Date:
February 2015
Related Keywords:
- Glioblastoma Multiforme
- Glioblastoma
Name | Location |
|---|---|
| University of Michigan | Ann Arbor, Michigan 48109-0624 |
| Medical College of Wisconsin | Milwaukee, Wisconsin 53226 |
| The University of Chicago | Chicago, Illinois 60637 |
| NorthShore University health system | Evanston, Illinois 60201 |
| Waukesha health care | Waukesha, Wisconsin 53188 |
