Clinical trial NCT00979017: Avastin/Temozolomide/Irinotecan for Unresectable/Multifocal Glioblastoma Multiforme
Official title: Avastin in Combination With Temozolomide and Irinotecan for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Gliosarcoma
Keywords: malignant glioma
glioblastoma multiforme
gliosarcoma
Avastin
bevacizumab
Temodar
temozolomide
Irinotecan
CPT-11
Pro00019065
Vredenburgh
Duke
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2009-09-17
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to determine the efficacy of Avastin in combination with temozolomide and irinotecan in terms of response rate. The secondary objectives are to describe the overall and progression-free survivals of unresectable patients treated with upfront Avastin, temozolomide and irinotecan and to assess the safety of Avastin, temozolomide and irinotecan in unresectable glioblastoma patients.

This is a phase II study with the combination of Avastin, temozolomide and irinotecan for unresectable or multifocal World Health Organization (WHO) grade IV malignant glioma patients. Patients will receive up to four cycles of Avastin, temozolomide and irinotecan. Approximately 41 subjects will take part in this study at Duke.


Eligibility criteria: Inclusion Criteria:

* Patients must have histologically confirmed diagnosis of WHO grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients will be unresectable or have multifocal disease.
* Age \> or = to 18 years and a life expectancy of \>12 weeks.
* Evidence of measurable primary Central Nervous System (CNS) neoplasm on contrast enhanced MRI.
* An interval of at least one week between prior biopsy or four weeks from surgical resection and enrollment on this protocol.
* Karnofsky \> or = to 60%.
* Hemoglobin \> or = to 9g/dl, absolute neutrophil count (ANC) \> or = to 1,500 cells/microliter, platelets \> or = to 125,000 cells/microliter.
* Serum creatinine ≤ 1.5 mg/dl, serum serum glutamic oxaloacetic transaminase (SGOT) and direct bilirubin ≤ 1.5 times upper limit of normal (if the total bilirubin is greater than or equal to 1.5 x the upper limit of normal, then the direct bilirubin must be ≤ 1.5 x the upper limit of normal).
* Signed informed consent approved by the Institutional Review Board prior to patient entry.
* If sexually active, patients will take contraceptive measures for the duration of the treatments.

Exclusion Criteria:

* Pregnancy or breast feeding
* Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.
* Active infection requiring IV antibiotics.
* Treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor.
* Evidence of \> grade 1 CNS hemorrhage on baseline MRI or CT scan.

Avastin-specific Exclusion Criteria:

* 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
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* 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
* Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
* Symptomatic peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or 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
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
* Serious, non-healing wound, ulcer, or bone fracture
* Proteinuria at screening as demonstrated by either urine protein:creatinine (UPC) ratio \> or = to 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
* Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential

Primary outcomes:
measure: Response Rate
timeFrame: 4 months
Secondary outcomes:
measure: Incidence and Severity of Central Nervous System (CNS) Hemorrhage and Systemic Hemorrhage
timeFrame: 4 months
measure: Incidence of Grade ≥ 4 Hematologic and ≥ Grade 3 Non-hematologic Toxicities
timeFrame: 4 months
measure: Median Progression-free Survival (PFS)
timeFrame: 36 months
measure: Median Overall Survival (OS)
timeFrame: 36 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Katherine B Peters, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Peters KB, Lou E, Desjardins A, Reardon DA, Lipp ES, Miller E, Herndon JE 2nd, McSherry F, Friedman HS, Vredenburgh JJ. Phase II Trial of Upfront Bevacizumab, Irinotecan, and Temozolomide for Unresectable Glioblastoma. Oncologist. 2015 Jul;20(7):727-8. doi: 10.1634/theoncologist.2015-0135. Epub 2015 May 29.