2 DG Trial

2 DG Trial:

A randomized controlled comparative trial to evaluate the efficacy and safety of 2-Deoxy –D- Glucose (2DG) as a radiomodifier in the treatment of Glioblastoma Multiforme.

Back ground:
The prognosis of patients suffering from malignant cerebral gliomas has remained dismal despite application of multimodal therapy and many advances in medical radiation technology.Radiation therapy for malignant astrocytomas (anaplastic astrocytoma and glioblastoma multiforme) has generally increased the median survival from about 4 to 10 months. There has been no breakthrough in the management of these highly malignant tumors during last several decades
The failure of radiotherapy in cerebral gliomas is primarily due to the presence of hypoxic, repair proficient and intrinsically radio resistant subpopulations of cells in the tumor.
2-deoxy-d-glucose (2-DG) sensitizes tumor cells to radiation. Therefore, in its presence the dose of radiation needed to produce a specified effect on the tumor is reduced. As the adverse effects of radiation depend on its total dose, hypofractionation in the effective dose of radiation means better tolerability, and improved quality of life, with out compromising efficacy.

Objective:
A) Primary Objective:
The mean survival time on 2-DG + Radiation Therapy arm vs Radiation Therapy alone arm.
B) Secondary Objective:
The Quality of Life (QoL) on 2-DG + Radiation Therapy arm as measured by KPS and FACT-BR compared with Radiation Therapy alone arm.
Study design:
A total of 100 patients will be included from 10 centers across the country.
Phase 1 and 2 studies have shown that a dose of 200-300 mg/kg of 2-DG, given orally 20-30 minutes before radiation, allows the standard radiation dose of 60 Gy (2 Gy daily, 5 days a week, for 6 weeks) to be hypofractionated to 35 Gy (5 Gy once a week for 7 weeks). This hypofractionated radiation dose seems to have somewhat better efficacy (mean survival time) and less radiation adverse effects, improving the quality of patient’s life during the survival.
The proposed phase 3, randomized, parallel-group, controlled trial is intended to verify the efficacy and tolerability of a hypofractionated radiation dose (35 Gy) in combination with 2-DG (T) in comparison with the standard radiation dose (60 Gy) (R) alone in the treatment of glioblastomas (WHO grade IV).

Inclusion Criteria
Patients will be included in the study if they meet all the following criteria:
- Give written informed consent before any procedures that are exclusively study related are conducted.
- Persons of either sex aged 18-75 years.
- Be able and willing, in the view of the investigator, to comply with all study procedures.
- Histopathological diagnosis of Glioblastoma (WHO grade IV).
- Patients with a post operative Karnofsky score of =70
(Surgery includes biopsy only, decompression, partial excision, near total excision, total excision

Exclusion Criteria
Patients will be excluded from the study if they meet any of the following criteria:
- Pregnant or lactating women.
- Patients with
- Uncontrolled hypertension, diabetes mellitus or cardiac disease.
- Serum Creatinine levels > 1.5 times the upper limit of normal.
- AST, ALT, AP or serum bilirubin levels > 2.5 times the upper limit of normal.
- History of cancer, excluding non-melanoma skin cancer or cervical cancer in situ.
- Prior, concurrent or adjuvant chemotherapy.

Present Status:
- This study recently completed accrual.
- Interim analysis of the trial is being done.