High-Grade Gliomas Clinical Trial
Official title:
A Phase II Trial of Bevacizumab and Irinotecan for Patients With Recurrent High-Grade Gliomas Immediately Following Tumor Progression After Treatment w/Bevacizumab Alone: A Companion Trial to NCI Study 06-C-0064 (NCT00271609)(Bevacizumab Alone for Recurrent Gliomas)
Background:
- Bevacizumab is a genetically engineered antibody that blocks the growth of new blood
vessels in tumors. It has shown activity against human brain tumors in laboratory tests
and human clinical trials.
- Irinotecan causes damage to the deoxyribonucleic acid (DNA) in cancer cells so that the
cells cannot reproduce or repair themselves. It is approved for treating patients with
colorectal cancer.
- Bevacizumab and irinotecan in combination are more effective against colon cancer than
either drug alone.
Objectives:
- To determine the safety of bevacizumab and irinotecan and any side effects associated
with the combination of the two drugs when given to patients with high grade gliomas.
- To determine if the combination of bevacizumab and irinotecan can help patients with
brain tumors that have grown after treatment with bevacizumab alone.
Eligibility:
-Patients 18 years of age and older who have been treated on National Cancer Institute (NCI)
trial 06-C-0064 (NCT00271609), "Bevacizumab Alone for Recurrent Gliomas," and whose tumor
has progressed.
Design:
Participants receive infusions of bevacizumab and irinotecan through a vein once every 2
weeks in 4-week treatment cycles, plus the following procedures:
- History, physical and neurological examinations every 2 weeks for the first treatment
cycle and then every 4 weeks
- Magnetic Resonance Imaging (MRI) scan of the head every 4 weeks.
- Routine lab every week.
- Quality-of-life questionnaire every 4 weeks
| Status | Terminated |
| Enrollment | 31 |
| Est. completion date | March 2010 |
| Est. primary completion date | January 2010 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
- INCLUSION CRITERIA: Patients must have been treated on the National Cancer Institute (NCI) trial 06-C-0064 (NCT00271609); bevacizumab alone for recurrent gliomas and now have evidence for tumor progression by magnetic resonance imaging (MRI) scan. Patients with histologically proven intracranial malignant glioma will be eligible for this protocol. Malignant glioma include glioblastoma multiforme (GBM), gliosarcoma, anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified). Patients must have evidence for tumor progression by 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 magnetic resonance (MR)/CT is required. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement. Patients must be greater than or equal to 18 years old, and with a life expectancy greater than 8 weeks. All patients or their previously designated durable power of attorney (DPA) (if the patient is deemed by the treating physician to be impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have a Karnofsky performance status of greater than or equal to 60. Patients must not be more than 4 weeks since their last bevacizumab treatment and may have received no form of treatment (i.e. radiation, chemotherapy, surgery, investigational therapy) for their progressive tumor between their last bevacizumab treatment and enrollment of this companion trial. Patients must have adequate bone marrow function (white blood cell (WBC) greater than or equal 3,000/microl, absolute neutrophil count (ANC) greater than or equal to1,500/mm^3, platelet count of greater than to or equal 100,000/mm^3), and hemoglobin greater than or equal to 10 gm/dl), adequate liver function (serum glutamic oxaloacetic transaminase (SGOT) and bilirubin less than 2.5 times upper limits of normal (ULN)), and adequate renal function (creatinine less than 1.5 mg/dL and/or creatinine clearance greater than or equal to 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. 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 patients' ability to tolerate this therapy. This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. No exclusion to this study will be based on race. Urine protein should be screened by dipstick or urine analysis for Urine Protein Creatinine (UPC) ratio. For proteinuria greater than or equal to 1+ or urine protein:creatinine UPC ratio greater than 1.0, 24-hour urine protein should be obtained and the level should be less than 1000 mg for patient enrollment. Subjects must be willing and able to practice adequate contraception. EXCLUSION CRITERIA: Concurrent use of other standard chemotherapeutics or investigative agents. Patients who have an active infection. Pregnant (positive pregnancy test) or nursing women. Both fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 6 months after the completion of bevacizumab therapy. Concurrent anti-coagulation or anti-platelet medication (including aspirin, non-steroidal anti-inflammatories, cyclooxygenase-2 (COX-2) inhibitors). Serious or non-healing wound, ulcer or bone fracture. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days. Invasive procedures defined as follows: - Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy - Anticipation of need for major surgical procedures during the course of the study - Core biopsy within 7 days prior to day (D)1 therapy Patients with clinically significant cardiovascular disease: - History of cerebrovascular accident (CVA) within 6 months - Uncontrolled hypertension (greater than 150/100 mmHg) - Myocardial infarction or unstable angina within 6 months - New York heart association grade II or greater congestive heart failure - Serious cardiac arrhythmia requiring medication - Unstable angina pectoris - Clinically significant peripheral vascular disease Clinical evidence of bleeding diathesis or coagulopathy. Patients with known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Cancer Institute (NCI) |
United States,
Barker D, Wright E, Nguyen K, Cannon L, Fain P, Goldgar D, Bishop DT, Carey J, Baty B, Kivlin J, et al. Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Science. 1987 May 29;236(4805):1100-2. — View Citation
Bigner SH, Bjerkvig R, Laerum OD. DNA content and chromosomal composition of malignant human gliomas. Neurol Clin. 1985 Nov;3(4):769-84. Review. — View Citation
Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009 Feb 10;27(5):740-5. doi: 10.1200/JCO.2008.16.3055. Epub 2008 Dec 29. — View Citation
Kreisl TN, Zhang W, Odia Y, Shih JH, Butman JA, Hammoud D, Iwamoto FM, Sul J, Fine HA. A phase II trial of single-agent bevacizumab in patients with recurrent anaplastic glioma. Neuro Oncol. 2011 Oct;13(10):1143-50. doi: 10.1093/neuonc/nor091. Epub 2011 A — View Citation
Moss AR. Occupational exposure and brain tumors. J Toxicol Environ Health. 1985;16(5):703-11. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Radiographic Response Rate (Malignant Glioma Participants) | Definition of response: complete response (CR) is the complete disappearance of all measurable and evaluable disease. Partial response (PR) is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No response (SD, NR)does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two target lesions if too numerous over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline. | 23 months (date of first enrollment to 1 month after last progression) | No |
| Primary | Number of Participants With Toxicity as Measured by The National Cancer Institute (NCI) Common Toxicity Criteria v. 3.0. | Here is the number of participants with any toxicity, defined as any adverse events possibly, probably or definitely related to the investigational drugs. For the detailed list of investigational new drug (IND)-related toxicities and other serious adverse events, see the adverse event module. | 23 months (date of first enrollment to 1 month after last progression) | Yes |
| Primary | Radiographic Response Rate (Anaplastic Glioma Participants) | Definition of response: complete response (CR) is the complete disappearance of all measurable and evaluable disease. Partial response (PR) is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No response (SD, NR)does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two target lesions if too numerous over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline. | 23 months (date of first enrollment to 1 month after last progression) | No |
| Primary | Radiographic Response Rate (Glioblastoma Multiforme Participants) | Definition of response: complete response (CR) is the complete disappearance of all measurable and evaluable disease. Partial response (PR) is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No response (SD, NR)does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two target lesions if too numerous over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline. | 23 months (date of first enrollment to 1 month after last progression) | No |
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