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

NCT01004874 | Completed Phase 2 Results

• 1 other identifier: Pro00019960
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malignant Glioma; Glioblastoma; Gliosarcoma

Keywords

malignant glioma; glioblastoma; gliosarcoma; Avastin; bevacizumab; Topotecan; Hycamtin; Temozolomide; Temodar; Pro00019960; Vredenburgh; Duke; Desjardins

Outcome Measures

Primary Outcomes (1)

• 6-month Progression-free Survival

  Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.

  6 months

Secondary Outcomes (5)

• One and Two Year Overall Survival

  One year and two years

• Median Overall Survival

  27 months

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

  27 months

• 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

  27 months

• Median Progression-free Survival

  27 months

Study Arms (1)

Bevacizumab, XRT, Temozolomide, Topotecan

EXPERIMENTAL

Patients are treated with standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation. Following completion of radiation therapy, patients have a MRI and, if there is no evidence of disease progression, patients receive 12 cycles of Avastin, temozolomide, and topotecan. Beginning a minimum of 14 days after the last radiation treatment, the Avastin is dosed at 10 mg/kg every other week; temozolomide is given at 150 mg/m2 daily the first 5 days in combination with topotecan on days 2 through 6 at 1.5 mg/ m2 for patient not taking EIAEDs and 2.0 mg/ m2 for patients taking EIAEDs on days 2-6 of each 28-day.

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

Interventions

Bevacizumab DRUG

Bevacizumab (Avastin) at 10 mg/kg every other week during standard radiation therapy (XRT). Following XRT, bevacizumab will remain at 10 mg/kg every other week.

Also known as: Avastin

Bevacizumab, XRT, Temozolomide, Topotecan

Temozolomide DRUG

Daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation therapy (XRT). Following XRT, temozolomide will be dosed at 150 mg/m2 daily the first 5 days of each 28-day cycle.

Also known as: Temodar

Bevacizumab, XRT, Temozolomide, Topotecan

Radiation Therapy (XRT) RADIATION

Standard radiation therapy for approximately 6.5 weeks

Bevacizumab, XRT, Temozolomide, Topotecan

Topotecan DRUG

Following standard radiation therapy, patients will receive topotecan on days 2 through 6 of each 28-day cycle at a dose of 1.5 mg/m2 for patients not taking enzyme-inducing anti-epileptic drugs (EIAEDs) and 2.0 mg/m2 for patients taking EIAEDs.

Also known as: Hycamtin

Bevacizumab, XRT, Temozolomide, Topotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Duke University: lead
• Genentech, Inc.: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

The Preston Robert Tisch Brain Tumor Center at Duke

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center

MeSH Terms

Conditions

Glioma; Glioblastoma; Gliosarcoma

Interventions

Bevacizumab; Temozolomide; Radiotherapy; Topotecan

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Camptothecin; Alkaloids

Results Point of Contact

• Title: Dr. Annick Desjardins, MD, FRCPC
• Organization: Duke University Medical Center

annick.desjardins@duke.edu

9196846173

Study Officials

• Annick Desjardins, MD, FRCPC

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2009
• First Posted: October 30, 2009
• Study Start: December 30, 2009
• Primary Completion: July 1, 2012
• Study Completion: November 2, 2021
• Last Updated: April 13, 2022
• Results First Posted: January 18, 2013

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)