| Eligibility |
Inclusion Criteria:
- Male or female patients aged = 13 years to 17 years
- ECOG Performance Status of = 2
- Ability to provide written informed consent from patient guardian and informed assent
from patient; obtained prior to participation in the study and any related procedures
being performed
- Tolerate a 10g 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 neo-adjuvant 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 = 1cm 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.
- 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.
- 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.
Exclusion Criteria:
Inadequate organ function as defined by:
Hematology:
- Neutrophil count of </=1,000/mm3
- Platelet count of </= 100,000/mm3L
- Hemoglobin < 9 g/dL (transfusion to meet eligibility allowed)
Biochemistry:
- AST/SGOT and ALT/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
- Serum bilirubin > 1.5 x ULN
- Serum creatinine > 1.5 x ULN or 24-hour creatinine clearance < 50 ml/min
- G6PD (glucose-6-phosphate dehydrogenase) deficiency
- Baseline MUGA or ECHO < than the lower limit of the institutional normal. ECHO or MUGA
only done on patients with prior doxorubicin exposure.
- New York Heart Association (NYHA) Grade II or greater congestive heart failure (see
Appendix E)
- 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
- 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
- Actively receiving insulin or requiring finger stick glucose monitoring at time of
ascorbate infusion (unless an exception is granted by the IND sponsor, medical
monitor, and the PI).
- 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.
- Patients who are on the following drugs and cannot have a drug substitution:
flecainide, methadone, amphetamines, quinidine, warfarin 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 anti-cancer therapy or radiation therapy. Palliative radiation
therapy to non-target lesions is permitted.
- Females of childbearing potential (FOCBP) who are unwilling 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
- Male patients whose sexual partners are FOCBP 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 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
- 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.37
- Patients with any significant history of non-compliance to medical regimens or with
inability to grant a reliable informed consent
- Patients with GIST tumors and Kaposi sarcoma are excluded
- 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.
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