Gemcitabine Plus Ascorbate for Sarcoma in Adults

This study will enroll male and female patients 18 years old or older who have a 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 and
neo-adjuvant therapy for the treatment of sarcoma, must have been given. 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.

During screening, subjects will receive a test dose (15g) of ascorbate. If the test dose
results in any toxicity >/= CTCAE grade 3 or a significant medical event in the opinion of
the principal investigator, the patient will be considered a screen failure.

Subjects who pass screening will then receive ascorbate, 75g, on Days 1, 2, 8, 9, 15 and 16
of a 28-day cycle. Gemcitabine will be administered on Days 1, 8 and 15, after the infusion
of ascorbate. Concomitant treatment will continue for at least 6 cycles. Patients whose
disease has not progressed while receiving gemcitabine and ascorbate and who are tolerating
therapy may continue either single agent gemcitabine or concomitant treatment beyond 6 cycles
at the discretion of the investigator. Treatment will be terminated with progression of
disease. Disease will be assessed by CT of the chest, abdomen and pelvis or MRI of the lesion
every 2 cycles for progression.

Inclusion Criteria:

1. Male or female patients aged ≥ 18 years old

2. ECOG Performance Status of ≤ 2

3. Ability to provide written informed consent obtained prior to participation in the
study and any related procedures being performed

- Patients must meet the following laboratory criteria:

- Hematology:

- Neutrophil count of >1500/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

- Total serum calcium >/= LLN or if calcium is below LLN then corrected calcium for
serum albumin should be >/= LLN

- Serum potassium ≥ LLN

- Serum sodium ≥ LLN

- Serum albumin ≥ LLN or 3g/dl

4. Tolerate a 15g ascorbate infusion (screening dose)

5. Baseline MUGA or ECHO done only in subjects with prior doxorubicin exposure. The test
must demonstrate LVEF ≥ the lower limit of the institutional normal.

6. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
within 7 days of the first administration of study treatment and must be 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

7. 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 and 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.

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.

Exclusion Criteria:

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.