Radiosurgery and Avastin for Recurrent Malignant Gliomas

Malignant Glioma Clinical Trial

Official title:

Radiosurgery and Avastin for Recurrent Malignant Gliomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01017250
• Other study ID #: Pro00018943
• Status: Completed
• Phase: N/A
• First received: November 19, 2009
• Last updated: January 28, 2014
• Start date: December 2009
• Est. completion date: February 2012

Study information

• Verified date: January 2014
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: February 2012
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• History of malignant glioma (WHO Grade III or IV) of the brain treated with some combination of surgery, biochemotherapy and conventionally fractionated external beam radiotherapy

• Radiotherapy completed at least 6 months prior to recurrence

• Age 18 years and older

• New or enlarging contrast-enhancing and/or 18FDG-avid nodule, at least 1 cm diameter

• Estimated life expectancy of 3 months or longer

Exclusion Criteria:

• Avastin therapy within 21 days of start of participation

• Contraindication to Avastin therapy or brain MRI

• Presence of bleeding diathesis or coagulopathy

• History of prior arterial thrombotic event, myocardial infarction, angina, CVA, TIA, CABG angioplasty or stenting within 6 months.

• Inadequately controlled hypertension (defined as systolic blood pressure

• New York Heart Association (NYHA) Grade II or greater congestive heart failure

• Clinically significant vascular disease

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to onset of treatment

• Prior history of hypertensive crisis or hypertensive encephalopathy

• History of abdominal fistula or GI perforation within 6 months prior to onset of treatment

• Serious non-healing wound, active ulcer or untreated bone fracture

• Proteinuria demonstrated by Urine Protein Creatinine ratio > 1.0

• Pregnancy

Study Design

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

Related Conditions & MeSH terms

• Glioma
• Malignant Glioma

Intervention

Radiation:
• Stereotactic Radiosurgery (SRS)
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

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

Locations

Country	Name	City	State
United States	Duke University Medical Center, Radiation Oncology	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Central Nervous System (CNS) Toxicity	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.	2 months after Stereotactic Radiosurgery	Yes
Secondary	Progression-free Survival (PFS)	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.	1 year	No
Secondary	Radiographic Response at Month 2	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.	2 months after SRS	No
Secondary	Overall Survival(OS)	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.	2 years	No
Secondary	Change in Quality of Life From Baseline to 2 Months After Stereotactic Radiosurgery (SRS)	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.	2 months after SRS	No
Secondary	Cognition at 2 Months After Stereotactic Radiosurgery (SRS)as Measured by the Mini-Mental State Exam ( MMSE)	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.	2 months after SRS	No
Secondary	Cognition at 2 Months After Stereotactic Radiosurgery (SRS) as Measured by the Trail Making Test (TMT)	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.	2 months after SRS	No
Secondary	Performance Status at 2 Months After Stereotactic Radiosurgery (SRS)	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.	2 months after SRS	No
Secondary	Steroid Usage After Stereotactic Radiosurgery (SRS)	Number of patients using steroids at baseline and at 2 months after SRS.	2 months after SRS 2 months after SRS 2 months after SRS	No
Secondary	Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): K-trans	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.	1 week after SRS	No
Secondary	Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): K-trans	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.	2 months after SRS	No
Secondary	Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): AUC	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.	1 week after SRS	No
Secondary	Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): AUC	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.	2 months after SRS	No
Secondary	Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): EVF	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.	1 week after SRS	No
Secondary	Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): EVF	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.	2 months after SRS	No
Secondary	Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 1 Week After Stereotactic Radiosurgery (SRS): ADC	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.	1 week after SRS	No
Secondary	Dynamic Contrasted-enhanced MRI (DCE-MRI) Perfusion Indices at 2 Months After Stereotactic Radiosurgery (SRS): ADC	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.	2 months after SRS	No