Gemcitabine Plus Ascorbate for Sarcoma in Adults

Exclusion Criteria

• •8. Patients with metastatic bone sarcomas who have failed all available therapies that have demonstrated clinical benefit. Available therapies include but not limited to methotrexate, adriamycin and cisplatin for osteosarcoma and vincristine, adriamycin and Cytoxan, ifosfamide, etoposide (VAC/IE)for Ewing's sarcoma.
• •9. Previous exposure to Gemcitabine will only be allowed if there is no residual toxicity from previous treatments. Toxicity must be graded as 0 or 1 prior to study.
• •10. Patients must have had disease progression on or following their most recent treatment regimen or on presentation for the first time with locally advanced unresectable or metastatic disease.
• •1. G6PD (glucose-6-phosphate dehydrogenase) deficiency
• •2. New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
• •3. History of myocardial infarction or unstable angina within 6 months prior to Day 1
• •4. History of stroke or transient ischemic attack within 6 months prior to Day 1
• •5. Known CNS disease, except for treated brain metastasis: Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded
• •6. Actively receiving insulin or requiring fingerstick glucose monitoring at time of ascorbate infusion (unless an exception is granted by the IND sponsor, medical monitor, and the PI).
• •7. Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• •8. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• •9. Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential
• •10. Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs.
• •11. Other concurrent severe and/or uncontrolled medical conditions
• •12. Patients who have received chemotherapy or any investigational drug \< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
• •13. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study.
• •14. Concomitant use of any anti-cancer therapy or radiation therapy. Palliative radiation therapy to non-target lesions is permitted.
• •15. Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom.
• •16. Patients with a history of another primary malignancy within 2 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin
• •17. Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs.
• •18. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent.
• •19. Patients with GIST tumors and Kaposi's Sarcoma are excluded.
• •20. Patients with history of more than one symptomatic oxalate stone in the last 6 months or visible stone in the kidney or ureter on screening CT scan.