Avastin/Temozolomide/Irinotecan for Unresectable/Multifocal Glioblastoma Multiforme

NCT ID: NCT00979017

Last Updated: 2014-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2013-01-31

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.

Conditions

Glioblastoma Multiforme; Gliosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Avastin in combination with temozolomide and irinotecan

Avastin 10 mg/kg every 14 days. Temozolomide 200 mg/m2 daily x 5 days in a 28-day cycle. Irinotecan dose depends on whether the patient is on an enzyme-inducing antiepileptic drug (EIAED). EIAED 340 mg/m2 every other week and no EIAED 125 mg/m2 every other week. Irinotecan dose also depends on if the patient has the UGT 1A1 polymorphism (7/7). If so, they do not metabolize the irinotecan normally, so these patients will start out at a two dose level reduction. EIAED starting dose will be 275 mg/m2 and no EIAED starting dose will be 75 mg/ m2.

Group Type: EXPERIMENTAL

Avastin

Intervention Type: DRUG

Avastin, by intravenous infusion, 10 mg/kg every 14 days

Temozolomide

Intervention Type: DRUG

Oral temozolomide at 200 mg/m2 daily for 5 days

Irinotecan

Intervention Type: DRUG

Irinotecan, by intravenous infusion, every other week (dose dependent upon if taking enzyme-inducing anti-epileptic drugs or if a blood test indicates the patient has the UGT 1A1 polymorphism)

Interventions

Avastin

Avastin, by intravenous infusion, 10 mg/kg every 14 days

Intervention Type: DRUG

Temozolomide

Oral temozolomide at 200 mg/m2 daily for 5 days

Intervention Type: DRUG

Irinotecan

Irinotecan, by intravenous infusion, every other week (dose dependent upon if taking enzyme-inducing anti-epileptic drugs or if a blood test indicates the patient has the UGT 1A1 polymorphism)

Intervention Type: DRUG

Other Intervention Names

Avastin (bevacizumab); Temodar; CPT-11, Camptosar

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.

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Katy Peters

OTHER

Sponsor Role: lead

Responsible Party

Katy Peters

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Katherine B Peters, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26025933 (View on PubMed)

Related Links

http://www.cancer.duke.edu/btc/

The Preston Robert Tisch Brain Tumor Center

Other Identifiers

Pro00019065

Identifier Type: -

Identifier Source: org_study_id