Response Monitoring Trial in Patients With Suspected Recurrence of Glioblastoma

Randomized Metabolic Response Monitoring Trial in Patients With Suspected Recurrence of Glioblastoma FDOPA PET-CT

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.

Study Overview

• Status: Terminated
• Conditions: Glioma; Glioblastoma; Glioblastoma Multiforme
• Intervention / Treatment: Drug: FDOPA PET

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Institute PET Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard diagnostics without PET; Standard of care brain imaging modalities, predominantly MRI
Experimental: FDOPA PET-CT; PET-CT with administration of FDOPA as an experimental radiopharmaceutical. This arm includes standard of care imaging plus FDOPA PET-CT	Drug: FDOPA PET; [18F]FDOPA radiopharmaceutical will be intravenousely injected for PET-CT scanning of the brain.; Other 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy compared to standard diagnostics without PET	Imaging findings will be validated by histopathology, clinical follow-up and/or repetitive imaging. If no histopathology within 3 months is available, clinical follow-up and imaging findings will be used for validation. If within 6 months of randomization no clinical progression nor progression on other imaging modalities is found, the patient will be rated as "no disease present at time of imaging".	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of FDOPA PET on patient management	Overall and progression free survival will be assessed according to the standard of clinical care with a minimum follow-up time of two years after randomization. In this study protocol there are no pre-set follow-up algorithms, however in clinical routine a follow-up every three months is standard.	[ Time Frame: 7 years ]

Collaborators and Investigators

• Sponsor: The Methodist Hospital Research Institute
• Collaborators: University of California, Los Angeles
• Investigators: Principal Investigator: Daniel Lee, MD, PhD, The Methodist Hospital Research Institute

Publications and helpful links

Helpful Links

• Collaborator

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: June 24, 2014
• First Submitted That Met QC Criteria: June 24, 2014
• First Posted (Estimate): June 27, 2014

Study Record Updates

• Last Update Posted (Actual): August 17, 2018
• Last Update Submitted That Met QC Criteria: August 15, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Glioma; PET; GBM; Recurrence; Glioblastoma; Glioblastoma multiforme; FDOPA
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agents; Cariostatic Agents; Fluorides; Dihydroxyphenylalanine
• Other Study ID Numbers: Pro00009857; 121638 (Other Identifier: Principal Investigator); 1013-0158 (Other Identifier: HMRI IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan to share data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No