Ignite Creation Date:
2024-05-05 @ 11:38 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00096707
Status:
COMPLETED
Last Update Posted:
2009-04-29
First Post:
2004-11-12
Brief Title:
Dose Escalation Trial of 2-Deoxy-D-Glucose 2DG in Subjects With Advanced Solid Tumors
Sponsor:
Threshold Pharmaceuticals
Organization:
Threshold Pharmaceuticals
Study Overview
Official Title:
Phase I Dose Escalation Trial of 2-Deoxy-D-Glucose 2DG Alone and in Combination With Docetaxel in Subjects With Advanced Solid Malignancies
Status:
COMPLETED
Status Verified Date:
2009-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The objectives of this study are to evaluate the safety tolerability pharmacokinetics and biologic effect FDG PET preliminary efficacy of daily oral doses of 2DG with and without weekly docetaxel in subjects with advanced solid tumors
Detailed Description:
2-deoxy-D-glucose 2DG is a synthetic glucose analog under development by Threshold Pharmaceuticals Inc that exploits the differences in metabolism between normal and malignant cells Malignant cells utilize glucose at a much higher rate than normal cells and are therefore more dependent on aerobic and anaerobic glycolysis If glycolysis could be blocked preferentially in malignant cells 2DG would have potential for anti-tumor therapy Hypoxic cells are especially dependent on anaerobic glycolysis and are generally resistant to anti-tumor therapies such as chemotherapy and radiotherapy Therefore combining 2DG with chemotherapy may be a way to simultaneously target both hypoxic and aerobic cells in tumors
Four factors may play a role in the preferential toxicity of 2DG in malignant cells 1 increased uptake and retention of glucose analogs by malignant cells 2 relative hypoxia of tumor cells relative to normal cells 3 malignant cells may be more sensitive to glucose deprivation than normal cells and 4 inhibition of glycolysis may increase sensitivity to some cytotoxic agents Preliminary data in human tumor xenografts support this hypothesis
Because 2DG is most likely to be effective in combination with chemotherapy this trial was designed to evaluate the maximum tolerated dose MTD of 2DG both alone and in combination with chemotherapy Docetaxel was chosen because there is evidence in human tumor xenografts of delayed tumor growth for 2DG in combination with paclitaxel compared to paclitaxel alone and it has been reported that taxanes may enhance uptake of 2DG into malignant cells Patients with advanced solid tumors were chosen because they are appropriate candidates for a Phase I clinical trial and because their tumors are likely to have areas of hypoxia
Four factors may play a role in the preferential toxicity of 2DG in malignant cells 1 increased uptake and retention of glucose analogs by malignant cells 2 relative hypoxia of tumor cells relative to normal cells 3 malignant cells may be more sensitive to glucose deprivation than normal cells and 4 inhibition of glycolysis may increase sensitivity to some cytotoxic agents Preliminary data in human tumor xenografts support this hypothesis
Because 2DG is most likely to be effective in combination with chemotherapy this trial was designed to evaluate the maximum tolerated dose MTD of 2DG both alone and in combination with chemotherapy Docetaxel was chosen because there is evidence in human tumor xenografts of delayed tumor growth for 2DG in combination with paclitaxel compared to paclitaxel alone and it has been reported that taxanes may enhance uptake of 2DG into malignant cells Patients with advanced solid tumors were chosen because they are appropriate candidates for a Phase I clinical trial and because their tumors are likely to have areas of hypoxia
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None