Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Tumor Volume \< 2.0cm receives 24 Gy in 1 fraction Tumor Volume 2.0-2.9cm receives 18 Gy in 1 faction Tumor Volume 3.0-4.9cm receives 25 Gy in 5Gy/fraction

Stereotactic Radiosurgery (SRS)

Bevacizumab (Avastin) 10 mg/kg given the day before SRS and 2 weeks after SRS

John Kirkpatrick, MD, PhD

The purpose of this study is to assess the central nervous system (CNS) toxicity in patients with recurrent malignant gliomas treated with concurrent Avastin and stereotactic radiosurgery (SRS).

In this pilot study, 15 human subjects with recurrent, unifocal malignant gliomas up to 5-cm in maximum dimension no longer responding to conventional chemotherapy but able to tolerate further chemotherapy will be enrolled. The primary endpoint of this study will be the proportion of patients who experience CNS toxicity, with secondary endpoints progression-free survival, overall survival, steroid dosage, development of radionecrosis, quality of life, objective radiographic response and performance status.

Radiosurgery and Avastin for Recurrent Malignant Gliomas

Number of participants who experience Grade 3 or higher adverse events in the "Nervous System Disorder" domain of Common Toxicity Criteria for Adverse Events (CTCAE) v4.0.

Time in months from the start of stereotactic radiosurgery (SRS) to the date of first progression according to Revised Assessment in Neuro-Oncology (RANO)criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Per RANO, progression is defined as a 20% increase in the sum of the longest diameter of target lesions,or a measurable increase in a non-target lesion or the appearance of new lesions.

Radiographic response at 2 months after stereotactic radiosurgery (SRS) assessed by MRI and based on modified Response Assessment in Neuro-Oncology (RANO) criteria.Per RANO, complete response (CR) is the disappearance of all target lesions;Partial Response(PR)is a \>=30% decrease in the sum of the longest diameter of target lesions.

Time in months from the start of stereotactic radiosurgery (SRS) to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.

Quality of life as measured by the change in Functional Assessment of Cancer Therapy-Brain (FACT-Br) scores from baseline to 2 months after SRS. The FACT-Br (version 4) is comprised of the Functional Assessment of Cancer Therapy-General (FACT-G), a 27-item core questionnaire evaluating the domains of physical, family/social, emotional and functional well-being, with the addition of 23 brain cancer specific questions. The FACT-G total score is the sum of the four FACT-G domain scores. The Brain Cancer Subscale (BrCS) is the sum of 19 brain cancer specific questions. The FACT-Br Trial Outcome Index (TOI) is the sum of the BrCS score and the physical and family/social domain scores. The FACT-Br total score is the sum of the FACT-G total score and the BrCS score. Higher scores for all scales indicate improved quality of life (QOL).Change score = score at 2 months after SRS - score at baseline. Positive change scores indicate improved quality of life.

Cognition as measured by the change in the Mini-Mental State Exam (MMSE) scores from baseline to 2 months after SRS. The MMSE is an 11-item measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall and language. The maximum score is 30. Change score = score at 2 months after SRS - score at baseline. Higher scores for this scale indicate improved quality of life(QOL). Positive change scores indicate improved cognition.

Cognition as measured by the change in scores on the Trail Making Test (TMT). The TMT consists of two parts. Part A (TMT-A) requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for Part B (TMT-B) except the person must alternate between numbers and letters (e.g., 1, A, 2, B, 3, C, etc.). The score on each part represents the amount of time required to complete the task. Shorter time scores indicates improved cognition. Change score = score at 2 months after SRS - score at baseline. Negative change scores indicate improved cognition.

Number of patients with a 10% decline in Karnofsky Performance Status (KPS) from baseline to 2 months after SRS. KPS is rated on a 0 to 100 scale representing a patient's ability to perform normal activity, ability to do active work, and the need for assistance. A score of 100 is "perfect" health and 0 represents death.

Number of patients using steroids at baseline and at 2 months after SRS.

DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. K-trans is the widely accepted MR method for quantitating brain tumor microvascular permeability( a measure of blood transport.) K-trans will indicate a combination of both flow and permeability properties of tissue. K-trans will indicate the tissue perfusion per unit volume, with a reduction in K-trans suggesting an increased anti-tumor effect and potentially improved outcome. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.

DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. K-trans is the widely accepted MR method for quantitating brain tumor microvascular permeability( a measure of blood transport.) K-trans will indicate a combination of both flow and permeability properties of tissue. K-trans will indicate the tissue perfusion per unit volume with a reduction in K-trans suggesting an increased anti-tumor effect and potentially improved outcome. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.

DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Area under the curve (AUC) is utilized to measure the signal enhancement ratio washout volume and could be predictive of cancer treatment response. It is possible AUC could be used as a prognostic indicator of the eventual response. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.

DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. By measuring extracellular extravascular volume fraction (EVF) it is possible to gain information on brain tissue perfusion. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.

DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.

DCE-MRI is a quantitative method that allows for non-invasive analysis of tumor vascular characteristics. Diffusion-weighted imaging, dependent on motion of water molecules, provides information regarding tissue integrity. Apparent diffusion coefficient (ADC) values in the normal brain parenchyma, and those in brain tumors were measured. Patients had a DCE-MRI at baseline and at 1 week and 2 months after SRS.

Genentech, Inc.

Duke University

Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).

SRS is

Stereotactic Radiosurgery

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

The number of participants with CNS toxicity is reported.

Central Nervous System (CNS) Toxicity

Progression-free Survival (PFS)

Complete response

Partial Response

Stable Disease

Progressive Disease

Not Evaluable

Radiographic Response at Month 2

Overall Survival(OS)

FACT-G: physical well-being ( range: 0-28)

FACT-G: Family/Social Well-being ( range: 0-28)

FACT-G: Emotional Well-being ( range: 0-24)

FACT-G: Functional Well-being ( range: 0-28)

FACT-G: Total Score ( range: 0-108)

FACT-Br: BrCS ( range: 0-76)

FACT-Br: TOI ( range: 0-132)

FACT-Br: Total Score ( range: 0-184)

Intent to Treat; only 10 patients out of 15 completed the month 2 questionnaire.

Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)

Intent to Treat: only 14 patients out of 15 completed the month 2 questionnaire

Cognition at 2 Months After Stereotactic Radiosurgery (SRS)as Measured by the Mini-Mental State Exam ( MMSE)

TMT-A

TMT-B

Intent to treat: only 14 of 15 patients completed the month 2 questionnaire

Cognition at 2 Months After Stereotactic Radiosurgery (SRS) as Measured by the Trail Making Test (TMT)

Intent to Treat: only 13 out of 15 patients completed month 2 KPS scores

Performance Status at 2 Months After Stereotactic Radiosurgery (SRS)

Baseline

2 months after SRS

Steroid Usage After Stereotactic Radiosurgery (SRS)

This was a test on the change from baseline to the post-SRS time point for all patients.

One week post SRS

Avastin 10 mg/kg given intravenously (IV) within 24 hours before and two weeks following their first treatment with Stereotactic Radiosurgery (SRS).

Intent-to-treat; only 12 of 15 patients had DCE-MRI results at both time points.

Spots Global Cancer Trial Database for Radiosurgery and Avastin for Recurrent Malignant Gliomas

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial