Response Monitoring Trial in Patients With Suspected Recurrence of Glioblastoma

NCT ID: NCT02176720

Last Updated: 2018-08-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2016-03-31

Brief Summary

It was previously shown that [18F]Fluorodopa (FDOPA) PET imaging results in intended management changes in 41% of brain tumor patients. However, its impact on patient outcome defined as survival, costs, and/or quality of life has not been demonstrated. Regulatory agencies require randomized trials to determine the impact of PET on patient management and outcome. In this study we hypothesize that the addition of FDOPA PET will improve patient outcome by more accurately identifying presence or absence of tumor recurrence than conventional imaging.

Detailed Description

Malignant gliomas are aggressive primary brain tumors that almost always lead to rapid patient deterioration and death. Timely diagnosis of recurrent disease as well as accurate monitoring of therapeutic responses is critically important in glioblastoma patients.

Despite introduction of new treatment approaches patient prognosis is poor with less than half of the patients being progression-free during the first 6 months after diagnosis of disease recurrence (6-month-progression-free survival rates of 46%).

The current diagnostic standard of care for diagnosing and monitoring brain tumors is contrast-enhanced, multi-planar magnetic resonance imaging (MRI). However, the ability of MRI for early detection of disease recurrence or progression is limited. Moreover, determination of treatment responses is difficult since benign tissue changes after radiation and/or chemotherapy can have the appearance of tumor recurrence or progression on MRI. Positron emission tomography (PET) is an established imaging technique that utilizes small amounts of radioactivity attached to very minimal amounts of substances (tracers) that are injected via a hand or arm vein. These substances can track certain features of cancers that can be visualized by using the PET-CT scanner. For instance, a number of different PET-tracers have been used to study brain tumor metabolism and to detect primary or recurrent tumors. These include tracers of glucose ([18F]FDG) and amino acid metabolism (e.g., [11C] methionine and [18F]FDOPA). Metabolic imaging of brain tumors with amino acid analogues has advantages over FDG. Since FDG assess glucose metabolism and the normal brain consumes a lot of glucose it can be difficult to detect tumors against high glucose use of normal brain tissue. FDOPA has been successfully used clinically for many years. The advantage of FDOPA is that normal brain tissue consumes very little FDOPA. Thus, tumors can be seen easily against a low background activity.

FDOPA PET imaging detects brain tumors with a very high accuracy and affects the management of 40% of patients. However, its impact on patient outcome defined as survival, costs, and/or quality of life has not been demonstrated.

Randomized trials are needed to evaluate the impact of PET on patient management and outcome. We will determine this by randomizing patients with suspected recurrence of glioblastoma into those who are managed using conventional diagnostic imaging versus those who will receive conventional imaging plus FDOPA PET. Randomization is like flipping a coin. Patients will have a 50% chance to undergo standard imaging or standard imaging combined with FDOPA PET.

Approximately 25-40% of the patients with suspected tumor recurrence will have pseudo-progression on MRI (i.e., the images suggest that there is tumor recurrence when there is in fact no recurrence). These patients will have correctly negative FDOPA PET scans. In these patient initiation of treatment can be postponed. In contrast, patients with positive FDOPA PET scans will undergo some kind of treatment at the discretion of the treating physician (radiation therapy, chemotherapy or surgery). We will find out whether the management and treatment change that is based on FDOPA PET affects the survival of patients and affects the costs of caring for the patients.

Conditions

Glioma; Glioblastoma; Glioblastoma Multiforme

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Standard diagnostics without PET

Standard of care brain imaging modalities, predominantly MRI

Group Type: NO_INTERVENTION

No interventions assigned to this group

FDOPA PET-CT

PET-CT with administration of FDOPA as an experimental radiopharmaceutical. This arm includes standard of care imaging plus FDOPA PET-CT

Group Type: EXPERIMENTAL

FDOPA PET

Intervention Type: DRUG

\[18F\]FDOPA radiopharmaceutical will be intravenousely injected for PET-CT scanning of the brain.

Interventions

FDOPA PET

\[18F\]FDOPA radiopharmaceutical will be intravenousely injected for PET-CT scanning of the brain.

Intervention Type: DRUG

Other Intervention Names

FDOPA PET-CT; Fluorine-18-L-dihydroxyphenylalanine; Fluorine-18-L-dihydroxyphenylalanine PET; Fluorine-18-L-dihydroxyphenylalanine PET-CT; [18F]FDOPA; [18F]FDOPA PET; [18F]FDOPA PET-CT

Eligibility Criteria

Inclusion Criteria

• Suspected first recurrence of a glioblastoma tumor by clinical measures and/or MRI
• Age 18 and older

Exclusion Criteria

• Breast feeding/ Pregnancy
• Severe psychiatric illness
• Primary diagnosis of a glioblastoma

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

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

The Methodist Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Lee, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The Methodist Hospital Research Institute

Locations

Houston Methodist Research Institute PET Center

Houston, Texas, United States

Countries

United States

Related Links

https://clinicaltrials.gov/ct2/show/study?term=FDOPA&rank=10

Collaborator

Other Identifiers

121638

Identifier Type: OTHER

Identifier Source: secondary_id

1013-0158

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00009857

Identifier Type: -

Identifier Source: org_study_id