Gemcitabine Hydrochloride and Ascorbic Acid in treating Participants with Locally Advanced, Unresectable, or Metastatic Soft Tissue or Bone Sarcomas

Inclusion Criteria

• Male or female patients aged >= 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Tolerate a 15 g ascorbate infusion (screening dose)
• Any patient with the diagnosis of locally advanced, unresectable or metastatic soft tissue or bone sarcoma (except GIST and Kaposi’s) from any site. A minimum of 1 prior chemotherapy regimen, including adjuvant or neoadjuvant therapy for the treatment of sarcoma. Patients eligible for an anthracycline should have received a prior anthracycline containing regimen. Patients who decline or are not eligible for anthracycline treatment may be considered for this protocol as a first line treatment. Patients with a diagnosis of liposarcoma should also have received eribulin if they received anthracycline-based therapy prior to eribulin. Patients with a diagnosis of myxoid liposarcoma should have received trabectedin. Patients with angiosarcoma should have received either Taxol or docetaxel. Patients must have measurable disease defined as at least 1 lesion >= 1 cm in the greatest dimension
• 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
• 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
• Patients with NO known central nervous system (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 (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator [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

Exclusion Criteria

• Neutrophil count of =< 1500/mm^3
• Platelet count of =< 100,000/mm^3L
• Hemoglobin < 9 g/dL (transfusion to meet eligibility allowed)
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 2.5 x upper limit of normal (ULN) or > 5.0 x ULN if the transaminase elevation is due to disease involvement
• Alkaline phosphatase > 5 x ULN without known bony metastases
• Serum bilirubin > 1.5 x ULN
• Serum creatinine > 1.5 x ULN or 24-hour creatinine clearance < 50 ml/min
• Total serum calcium < lower limit of normal (LLN) or if calcium is below LLN then corrected calcium for serum albumin should be >= LLN
• Serum potassium < 3.0
• Serum sodium < 130
• Serum albumin < 2.5 g/dl
• G6PD (glucose-6-phosphate dehydrogenase) deficiency
• Prior exposure to gemcitabine for metastatic disease
• Subjects with prior doxorubicin exposure with a MUGA or echocardiogram (ECHO) demonstrating left ventricular ejection fraction (LVEF) < the lower limit of the institutional normal
• New York Heart Association (NYHA) grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to day 1
• History of stroke or transient ischemic attack within 6 months prior to day 1
• Actively receiving insulin or requiring fingerstick glucose monitoring at time of ascorbate infusion
• Patients on warfarin and unable to be substituted to another anticoagulant
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day 1
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Pregnancy (positive pregnancy test) or lactation
• Women of childbearing potential (WOCBP) who are not willing to use two methods of contraception one of them being a barrier method during the study and for 3 months after last study drug administration
• 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
• Other concurrent severe and/or uncontrolled medical conditions
• 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
• 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
• Concomitant use of any other anti-cancer therapy or radiation therapy. Palliative radiation therapy to non-target lesions is permitted
• 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
• Patients with prior malignancies of the same or different tumor type and patients with concurrent malignancies of the same or different tumor type whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational drug
• 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
• Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
• 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