ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma

Inclusion Criteria:

- Histologically or cytologically confirmed grade 2 or 3 soft tissue sarcoma that is
unresectable or metastatic that would be standardly treated with gemcitabine or
gemcitabine and docetaxel. Prior surgery for primary or metastatic disease after
chemotherapy following a response is allowed.

- Measurable disease defined as lesions that can be accurately measured in at least one
dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by
chest x-ray, or ≥ 10 mm with calipers by clinical exam.

- Treated with at least one line of systemic therapy in the palliative setting or with
neoadjuvant or adjuvant chemotherapy within the prior six months. The allowable window
between treatments is 21 days for chemotherapy or a TKI, or 5 ½ half-lives for a TKI
(whichever is shorter), 21 days and progression by CT for immunotherapy, 21 days for
RT, 21 days for surgery, or 28 days for an investigational agent.

- At least 18 years of age.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

- Normal bone marrow and organ function as defined below:

- Leukocytes ≥ 3,000/mcL

- Absolute neutrophil count ≥ 1,500/mcl

- Platelets ≥ 100,000/mcl

- Total bilirubin ≤ 2 x institutional upper limit of normal (IULN)

- AST(SGOT)/ALT(SGPT) ≤ 3 x IULN (or ≤ 5 x IULN if liver metastases are present)

- Creatinine ≤ 1.5 x IULN OR

- Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels
above institutional normal

- Serum uric acid ≤ 8 mg/dL (with or without medication control)

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry and for
the duration of study participation. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she must inform her treating physician
immediately.

- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

- A history of other high grade malignancy ≤ 5 years previous. Exceptions include basal
cell or squamous cell carcinoma of the skin which were treated with local resection
only or carcinoma in situ of the cervix, or other tumors discussed with the study PI

- Currently receiving any other investigational agents.

- Prior treatment with ADI-PEG 20, gemcitabine, or docetaxel

- Known brain metastases. Patients with known brain metastases must be excluded from
this clinical trial because of their poor prognosis and because they often develop
progressive neurologic dysfunction that would confound the evaluation of neurologic
and other adverse events.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to ADI-PEG 20, gemcitabine, pegylated compounds, or other agents
used in the study.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- History of seizure disorder not related to underlying cancer.

- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry.

- Known HIV-positivity on combination antiretroviral therapy because of the potential
for pharmacokinetic interactions with the study treatment. In addition, these patients
are at increased risk of lethal infections when treated with marrow-suppressive
therapy. Appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy when indicated.