Safety Study of 2DG With Stereotactic Radiosurgery

NCT00247403 | Withdrawn Phase 1 DMC

• 1 other identifier: 200506744
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Ionizing radiation produces cancer cell death by creating high levels of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, in irradiated cells. Cancer cells are preferentially affected by ROS. The investigators, therefore, propose that interfering with the detoxification of ROS will make radiation more toxic to cancer cells. Several cellular mechanisms exist to detoxify ROS, and glucose metabolism plays an important role in many of these mechanisms. The investigators propose that interfering with glucose metabolism will sensitize cancer cells to radiation. The investigators' central hypothesis is that 2DG will sensitize cancer cells to ionizing radiation by inhibiting the use of glucose to detoxify reactive oxygen species produced by radiation. As an initial step to evaluate this hypothesis, the investigators have designed this phase I study.

Conditions

Intracranial Neoplasms; Neoplasm Metastasis

Keywords

Intracranial cancer; Cancer; 2DG; 2-deoxyglucose; Intracranial metastatic cancer

Outcome Measures

Primary Outcomes (1)

• Safety

  During treatment and 30 days post-treatment

Study Arms (1)

2DG

EXPERIMENTAL

Drug: 2-deoxyglucose (2DG)

Interventions

2-deoxyglucose (2DG) DRUG

Addition of 2DG to stereotactic radiosurgery. Dose escalation study.

2DG

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document.
• Brain metastases from histologically confirmed extracranial cancer or previously confirmed intracranial carcinoma. Carcinoma must be staged using the American Joint Committee on Cancer (AJCC) staging criteria version 6.
• Morphologically well-defined tumor mass on computed tomography (CT)/magnetic resonance imaging \[MRI\] (largest diameter less than 40 mm) after resection.
• Intracranial mass or masses ≤ 4 cm in greatest diameter. Patients with multiple masses will be eligible if their radiosurgery treatment time is expected to last less than one hour (typically a maximum of 6 lesions).
• Standard institutional radiotherapeutic treatment is stereotactic radiosurgery delivered using bite-plate localization.
• Karnofsky greater than or equal to 70% at time of screening
• Life expectancy of greater than 3 months
• Subjects must have normal organ and marrow function as defined below:
• serum glucose \< 200 mg/dl
• hemoglobin A1C (HbA1c) \< 8.5 %
• Contraceptive use in men and women of childbearing potential prior to, and for the duration of, this study. The teratogenic effects of ionizing radiation are well documented, and 2DG has the potential for teratogenic or abortifacient effects.
• Nursing of infants must be suspended during the study. There is an unknown but potential risk for adverse events in infants nursing from patients treated with 2DG, therefore breastfeeding must be discontinued for the duration of the study.
• Ability to ingest 50 ml of fluid either by mouth or feeding tube.

You may not qualify if:

• Subjects with diabetes mellitus, elevated HbA1c or elevated blood glucose.
• Subjects requiring a headring ('halo') immobilization for standard stereotactic localization. Patients with metastases adjacent to optic chiasm, optic nerve or other radiosensitive tissue necessitating the accuracy of a headring will be excluded.
• Subjects must not be receiving any other investigational agents.
• Subjects with a history of myocardial infarction in the past year and/or dependent on beta-adrenergic blocking agents.
• Subjects with an uncontrolled seizure disorder.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the nursing mother with 2DG, breastfeeding must be discontinued while the nursing mother is treated.
• Pregnant women are excluded from this study. The teratogenic effects of ionizing radiation are well documented, and 2DG has the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative pregnancy test result immediately prior to the study and should they become pregnant or suspect that they are pregnant during the study, they must inform their treating physicians immediately.

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Neoplasm Metastasis; Neoplasms

Interventions

Deoxyglucose

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxy Sugars; Carbohydrates

Study Officials

• John M. Buatti, M.D.

  University of Iowa Hospitals & Clinics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair, Department of Radiation Oncology

Study Record Dates

• First Submitted: October 28, 2005
• First Posted: November 1, 2005
• Study Start: October 1, 2005
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: April 10, 2015

Record last verified: 2015-04

Locations

US (1)