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

Phase 1 Trial of ADI-PEG 20 Plus Doxorubicin in Patients With HER2 Negative Metastatic Breast Cancer or Advanced Solid Tumor

Certain cancers require the amino acid arginine. Arginine deiminase (ADI) is an enzyme from microbes that degrade arginine. ADI has been formulated with polyethylene glycol, and has been used to treat patients that have cancers that require arginine. In this study, ADI will be combined with the well known chemotherapy Doxorubicin and the safety and potential efficacy of this combination will be explored in patients with HER2 Negative Metastatic Breast Cancer.

Study Overview

• Status: Completed
• Conditions: HER2 Negative Metastatic Breast Cancer
• Intervention / Treatment: Drug: ADI-PEG 20

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77230
      • M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Biopsy proven HER2 negative metastatic breast cancer (dose escalation portion and MTD expansion portion) or advanced solid tumor (dose escalation portion).
2. 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.
3. Unresectable disease or subject refused surgery.
4. Measurable disease as assessed by RECIST 1.1 criteria (Appendix A).
5. Failed available therapy known to confer clinical benefit but no more than 4 prior lines of chemotherapy for metastatic disease.
6. Time to treatment failure from doxorubicin containing regimen ≥ 12 months if previously treated with doxorubicin.
7. Age ≥ 18 years.
8. ECOG performance status of 0 - 2. -

Exclusion Criteria:

1. 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.
2. Prior epirubicin exposure of > 600 mg/m2.
3. Pregnancy or lactation.
4. Expected non-compliance.
5. 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.
6. 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.
7. 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.
8. Subjects who had been treated with ADI-PEG 20 previously.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADI-PEG 20; arginine deiminase formulated with polyethylene glycol	Drug: ADI-PEG 20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events	Assessment of safety and tolerability of ADI-PEG 20 in combination with doxorubicin in HER2 negative metastatic breast cancer	2 years estimated - course of study
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

Collaborators and Investigators

• Sponsor: Polaris Group
• Investigators: Principal Investigator: Siqing Fu, MD, MD Anderson

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: September 11, 2013
• First Submitted That Met QC Criteria: September 19, 2013
• First Posted (Estimate): September 24, 2013

Study Record Updates

• Last Update Posted (Estimate): April 14, 2016
• Last Update Submitted That Met QC Criteria: April 13, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: HER2 Negative Metastatic Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: POLARIS2013-004