Ph 1 ADI-PEG 20 Plus Doxorubicin; Patients With HER2 Negative Metastatic Breast Cancer

Recruitment & Eligibility

Inclusion Criteria

Biopsy proven HER2 negative metastatic breast cancer (dose escalation portion and MTD expansion portion) or advanced solid tumor (dose escalation portion).
ASS deficiency (defined as <50% ASS expression) demonstrated on tissue specimen by Immunohistochemistry (IHC). Cytology and fine need aspirate specimens are not acceptable for ASS testing.
Unresectable disease or subject refused surgery.
Measurable disease as assessed by RECIST 1.1 criteria (Appendix A).
Failed available therapy known to confer clinical benefit but no more than 4 prior lines of chemotherapy for metastatic disease.
Time to treatment failure from doxorubicin containing regimen ≥ 12 months if previously treated with doxorubicin.
Age ≥ 18 years.
ECOG performance status of 0 - 2. -

Exclusion Criteria

Serious infection requiring treatment with systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment.
Prior epirubicin exposure of > 600 mg/m2.
Pregnancy or lactation.
Expected non-compliance.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness, social situations that would limit compliance with study requirements.
Subjects who have had any anticancer treatment prior to entering the study and have not recovered to baseline (except alopecia) or ≤ Grade 1 AEs, or deemed irreversible from the effects of prior cancer therapy. AEs > Grade 1 that are not considered a safety risk by the Sponsor and Investigator may be allowed upon agreement with both.
Subjects with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present in the opinion of the Investigator will not affect subject outcome in the setting of breast cancer diagnosis.
Subjects who had been treated with ADI-PEG 20 previously.

Study & Design

Arm && Interventions

Group	Intervention	Description
ADI-PEG 20	ADI-PEG 20	arginine deiminase formulated with polyethylene glycol

Primary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events	2 years estimated - course of study	Assessment of safety and tolerability of ADI-PEG 20 in combination with doxorubicin in HER2 negative metastatic breast cancer
Determine preliminary estimates of efficacy, measured by RECIST 1.1 criteria, for ADI-PEG 20 combo with doxorubicin in HER2 negative metastatic breast cancer.	2 years estimated - course of study

Secondary Outcome Measures

Name	Time	Method

Recruitment & Eligibility