Dose Escalation Trial of 2-Deoxy-D-Glucose (2DG) in Subjects With Advanced Solid Tumors

• Status: Completed
• Trial end date: 2008-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Threshold Pharmaceuticals
• Treatments: Deoxyglucose; Docetaxel

Criteria

Inclusion Criteria:

• Males and females, at least 18 years of age

• Histologically confirmed, locally advanced or metastatic solid malignancy

• Previously treated with at least one chemotherapy regimen for advanced or metastatic disease OR no curative standard treatment is available

• Recovered from reversible toxicities of prior therapy

• Life expectancy of at least 3 months

• ECOG performance status of 0, 1, or 2

• Measurable or nonmeasurable disease by RECIST criteria

• Ability to understand the purposes and risks of the study and having signed a written informed consent form

• All women of childbearing potential and all men must agree to use effective means of contraception from entry into the study through 3 months after the last dose

Exclusion Criteria:

• Previous or current CNS metastases (screening CT or MRI is not required in asymptomatic subjects)

• Active clinically significant infection requiring antibiotics

• Known glucose-6-phosphate dehydrogenase deficiency or history of anemia of unknown etiology

• History of clinically significant unexplained episodes of hypotension, fainting, dizziness, or lightheadedness

• History or symptoms of cardiovascular disease, particularly coronary artery disease, arrhythmias, or conduction defects with risk of cardiovascular instability, uncontrolled hypertension, clinically significant pericardial effusion, or congestive heart failure

• History of transient ischemic attack, stroke, or seizure disorder or any other CNS disease considered to be significant by the investigator

• Known autonomic dysfunction or chronic orthostatic hypotension

• Evidence of hypoglycemia, clinically significant renal disease, clinically significant liver disease (other than liver metastases), diabetes mellitus, gastrointestinal disorder (that could affect absorption or elimination of orally-administered medications), or obstructive uropathy with significant post-void residual during the past 5 years

• Known HIV infection

• Other primary malignancies (other than treated basal cell carcinoma of the skin or treated in situ cervical cancer) within the past 5 years

• Major surgery within 4 weeks of the start of study treatment, without complete recovery

• Antitumor therapy within 21 days of the start of study treatment

• Disease progression/relapse on docetaxel therapy within the past 12 months

• A history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80

• Known sensitivity to methylparaben or propylparaben

• Inability to discontinue prohibited medications for 24 hours before and after dosing on Day 1 of Weeks 1, 2, and 3 and Day 5 of Week 1. In addition, patients who cannot discontinue medications known to induce or inhibit CYP 3A4, such as cyclosporine, terfenadine, ketoconazole, erythromycin, and troleandomycin, for the duration of the study are not eligible.

• Peripheral neuropathy >= Grade 2

• Hemoglobin <9 g/dL

• ANC <1500/μL

• Platelet count <100,000/μL

• Total bilirubin >1.5 mg/dL

• Abnormal liver function

• Serum creatinine >1.5 mg/dL unless creatinine clearance is >= 60 mL/min

• Serum potassium < lower limit of normal

• Elevated fasting blood glucose

• Pregnant or nursing women

• Participation in an investigational drug or device study within 28 days of the first day of dosing on this study

• Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.

• Unwillingness or inability to comply with the study protocol for any other reason

• Subjects who live alone