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Avastin/Radiation (XRT)/Temozolomide (Temodar) Followed by Avastin/Temodar/Topotecan for Glioblastoma

Information source: Duke University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Malignant Glioma; Glioblastoma Multiforme; Gliosarcoma

Intervention: Bevacizumab (Drug); Temozolomide (Drug); Radiation Therapy (XRT) (Radiation); Topotecan (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Duke University

Official(s) and/or principal investigator(s):
Annick Desjardins, MD, FRCPC, Principal Investigator, Affiliation: Duke University

Summary

This is a phase II study of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan in grade IV malignant glioma patients.

Clinical Details

Official title: Avastin in Combination With Radiation and Temozolomide Followed by Avastin, Temozolomide, and Topotecan for Glioblastoma Multiformes and Gliosarcomas

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 6-month Progression-free Survival

Secondary outcome:

One and Two Year Overall Survival

Median Overall Survival

Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage

Number of Patients Experiencing a Greater Than or Equal to Grade 4 Hematologic or a Greater Than or Equal to Grade 3 Non-hematologic Toxicity

Median Progression-free Survival

Detailed description: The primary objective of this study is to use 6-month progression-free survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan in the treatment of grade IV malignant glioma patients following surgical resection. Secondary objectives are to determine the overall survival following the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan and to describe the toxicity of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan. The study will have survival and toxicity endpoints. Patients will be treated with standard radiation therapy and daily temozolomide for 6 and a half weeks of radiation. Avastin will be administered every other week beginning a minimum of 28 days after the last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of radiation therapy, patients will have a MRI and if there is no evidence of disease progression, patients will receive 12 cycles of Avastin, temozolomide, and topotecan (beginning a minimum of 14 days after the last radiation treatment). Subjects will be identified by the investigator as those patients who have newly diagnosed grade 4 malignant glioma (glioblastoma multiforme or gliosarcoma), and be within 6 weeks of the last major surgical procedure, craniotomy, open biopsy, or stereotactic biopsy. Fifty (50) patients will initially be accrued to the study and the overall efficacy of the treatment regimen assessed. Analyses will be conducted within subgroups defined by methylation status. Early side effects of radiation that may start during radiation include hair loss, scalp redness, inflammation of the ear canals, and fatigue. There is a small chance of long-term effects from radiation, occurring after months or years after completion. These may include worsening of mental function, hearing, vision, strength and coordination. In initial Phase I and II clinical trials, four potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage. Temozolomide has been well tolerated by both adults and children with the most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea and vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, and hepatotoxicity. With topotecan, reversible myelosuppression with leukopenia and thrombocytopenia is dose limiting. Nausea and vomiting, as well as diarrhea and alopecia, are frequent. Moderate fatigue, transient elevation of hepatic transaminase levels, stomatitis, anemia, fever, mucositis, flu-like symptoms, and rash have been reported.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients must have histologically confirmed diagnosis of WHO grade IV primary

malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be within 6 weeks of the last major surgical procedure.

- Age > or = to 18 years.

- An interval of at least 2 weeks and not > 6 weeks between prior major surgical

procedure and study enrollment.

- No prior radiotherapy or chemotherapy for a brain tumor

- Karnofsky > or = to 60%.

- Hemoglobin ≥ 9. 0 g/dl, absolute neutrophil count (ANC) ≥ 1,500 cells/microliter,

platelets ≥ 125,000 cells/microliter.

- Serum creatinine ≤ 1. 5 mg/dl, serum glutamic oxaloacetic transaminase (SGOT) and

bilirubin ≤ 1. 5 times upper limit of normal.

- Signed informed consent approved by the Institutional Review Board

- If sexually active, patients must agree to use appropriate contraceptive measures for

the duration of the study and for 6 months afterwards as stated in the informed consent. 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.

- Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of

the grade of the tumor.

- Evidence of > grade 1 central nervous system (CNS) hemorrhage on baseline MRI on CT

scan. Avastin-specific Exclusion Criteria:

- Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or

diastolic blood pressure > 100 mmHg)

- 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, requiring surgical repair or

recent peripheral arterial thrombosis) within 6 months prior to study enrollment

- History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month

prior to study enrollment

- Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic

anticoagulation)

- 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 within 6 months prior to

study enrollment

- Serious, non-healing wound, active ulcer, or untreated 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

- Pregnant (positive pregnancy test) or lactation. Use of effective means of

contraception (men and women) in subjects of child-bearing potential

Locations and Contacts

The Preston Robert Tisch Brain Tumor Center at Duke, Durham, North Carolina 27710, United States
Additional Information

The Preston Robert Tisch Brain Tumor Center

Starting date: December 2009
Last updated: August 3, 2015

Page last updated: August 23, 2015

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