Ph 1 Trial of ADI-PEG 20 Plus Docetaxel in Solid Tumors With Emphasis on Prostate Cancer and Non-Small Cell Lung Cancer

Inclusion Criteria: (Dose-Escalation Phase)

1. For the dose-escalation phase, patients must have cytologically or histologically
proven advanced malignant solid tumors, with emphasis on CRPC.

2. Patients must be 18 years of age or older.

3. Patients must have a Zubrod (ECOG) performance status of 0-2.

4. Patients must have an estimated survival of at least 3 months.

5. Any prior chemotherapy must have been completed at least 4 weeks prior to start of
treatment. Prior radiation must have been completed at least 2 weeks prior to start of
therapy. Patients must have recovered from acute reversible side effects of prior
chemotherapy regimens or radiotherapy to < grade 1 (excluding alopecia, lymphopenia,
and hyperglycemia) according to the National Cancer Institute Common Terminology
Criteria for Adverse Events (NCI-CTCAE), version 4.0.

6. Radiographs (Xrays, CT scans, etc) to follow disease response or progression must have
been completed within 28 days prior to registration.

7. Patients must have adequate renal function as documented by a calculated creatinine
clearance of > 45 ml/min (see Appendix for formula for calculating creatinine
clearance).

8. Patients must have adequate liver functions: AST and ALT < 2.5 X upper limit of
normal, and bilirubin < upper limit of normal.

Inclusion Criteria: MTD Expansion Phase Cohort 1 - CRPC

1. All patients must have a histologic diagnosis of adenocarcinoma of the prostate which
is measurable or non-measurable.

2. Patients must have metastatic prostate cancer deemed to be unresponsive or refractory
to hormone therapy by one or more of the following (despite androgen deprivation and
antiandrogen withdrawal when applicable):

- Progression of measurable disease assessed within 28 days prior to registration.

- Progression of non-measurable disease assessed within 28 days prior to
registration.

- Rising PSA - Rising PSA is defined as at least two consecutive rises in PSA to be
documented over a reference value (measure 1). The first rising PSA (measure 2)
must be taken at least 7 days after the reference value. A third confirmatory PSA
measure is required (2nd beyond the reference level) to be greater than the
second measure, and it must be obtained at least 7 days after the 2nd measure. If
this is not the case, a fourth PSA is required to be taken and be greater than
the second measure. The patient must have a PSA ≥ 5 ng/ml in addition to
increasing PSA to be eligible by rising PSA criteria alone. However, no minimum
PSA is required for patients whose progression is based on measurable or
non-measurable disease.

3. All patients must have a pre-study PSA obtained within 28 days prior to registration.

4. All patients must have had imaging studies within 28 days prior to registration. The
choice of imaging studies to follow disease will be at the discretion of the
investigator.

5. Patients must be offered the opportunity to participate in specimen banking for future
use (to include the serum and tissue correlative studies).

6. Patients must have been surgically or medically castrated. If method of castration is
LHRH agonists (leuprolide or goserelin) or LHRH antagonists, then the patient should
be willing to continue the use of LHRH agonists. Patients who have stopped treatment
should be willing to restart.

7. If the patient has been treated with non-steroidal antiandrogens (flutamide,
bicalutamide, nilutamide or ketoconazole), they must have been stopped at least 14
days prior to registration for ketoconazole and at least 28 days prior to registration
for flutamide, bicalutamide or nilutamide and the patients must have demonstrated
progression.

8. Prior, planned, or ongoing bisphosphonate therapy or denosumab is allowed.

Exclusion Criteria:

(Dose-Escalation Phase)

1. Pregnant or breastfeeding women. The effects of these drugs on the unborn fetus are
unknown. Documentation of a negative serum pregnancy test is required for all women of
reproductive potential.

2. Patient has a clinically significant concurrent illness. Patients must not have a
serious intercurrent medical or psychiatric illness, including serious active
infection.

3. Patient is currently enrolled in a different clinical study in which investigational
procedures are performed or investigational therapies are administered. Also, a
patient may not enroll in such clinical trials while participating in this study.

4. Patient has a history of allergy or hypersensitivity to the study drugs or a taxane.

5. Patient has serious medical risk factors involving any of the major organ systems such
that the investigator considers it unsafe for the patient to receive an experimental
research drug.

6. Prior therapy with ADI-PEG 20 or docetaxel.

7. Allergy to pegylated compounds or study drugs.

Exclusion Criteria: MTD Expansion Phase Cohort 1 - CRPC

1. Patient has a clinically significant concurrent illness. Patients must not have a
serious intercurrent medical or psychiatric illness, including serious active
infection.

2. Patient is currently enrolled in a different clinical study in which investigational
procedures are performed or investigational therapies are administered. Also, a
patient may not enroll in such clinical trials while participating in this study.

3. Patient has a history of allergy or hypersensitivity to the study drug or a taxane.

4. Patient has serious medical risk factors involving any of the major organ systems such
that the investigator considers it unsafe for the patient to receive an experimental
research drug.

5. Prior therapy with ADI-PEG 20 or docetaxel.

6. Allergy to pegylated compounds.