Ph 1 Trial of ADI-PEG 20 Plus Cisplatin in Patients With Metastatic Melanoma

Phase 1 Trial of ADI-PEG 20 Plus Cisplatin in Patients With Metastatic Melanoma or Other Advanced Solid Malignancies

Certain cancers require the amino acid arginine. Arginine deiminase (ADI) is an enzyme from microbes that degrades 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 cisplatin, and the safety and potential efficacy of this combination will be explored in patients with cancers that require arginine.

Study Overview

• Status: Completed
• Conditions: Cutaneous Melanoma, Uveal Melanoma, Ovarian Carcinoma or Other Advanced Solid Tumors
• Intervention / Treatment: Drug: ADI-PEG 20

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 704
    • NCKUH
• United States
  • Texas
    • Houston, Texas, United States
      • MD 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: All

Description

Inclusion Criteria:

1. Histologically confirmed diagnosis of advanced solid tumor (dose escalation component) or metastatic melanoma (uveal or cutaneous) (doses escalation and MTD expansion components) or platinum-resistant (tumor progression within a year after the completion of platinum-based therapy) ovarian carcinoma (high grade serous, endometrial or poorly differentiated endometrioid) or HCC that has failed treatment with sorafenib or did not tolerate sorafenib or refused sorafenib, or HCC with coexistent BCT that has or has not been treated with chemotherapy, or BCT that has or has not been treated with chemotherapy. For HCC and HCC with coexistent BCT, cirrhotic status of Child-Pugh grade A-B7 must be present. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix C). Subjects on anti-coagulants are to receive 1 point for their INR status, as they are presumed to have a <1.7 baseline PT/INR.
2. Ovarian cancer, or HCC, or HCC with coexistent BCT, or BCT only tissue either from an archived specimen or from a new biopsy of sufficient amount and quality should be available for IHC determination of ASS status to be performed retrospectively for the ovarian cancer, or HCC, or HCC with coexistent BCT, or BCT only cohorts. Subjects with no tissue available would require a biopsy.
3. Unresectable disease or patient refused surgery.
4. Progressive disease if treated with chemotherapy, radiotherapy, surgery or immunotherapy. If prior radiation was given, the measurable disease should be outside the radiation port. Unequivocal progression of HCC/BTC lesions previously treated with catheter-based therapy including transarterial chemoembolization or radioembolization is allowed.
5. Measurable disease as assessed by RECIST 1.1 criteria (Appendix A).
6. Age ≥ 18 years.
7. ECOG performance status of 0 - 1.
8. No prior systemic therapy, immunotherapy, investigational agent, chemoembolization, radioembolization or radiation therapy within the last 4 weeks.
9. Fully recovered from any prior surgery and no major surgery within 4 weeks of initiating treatment, except for gamma knife which can take place within 2 weeks. Surgery for placement of vascular access devices is acceptable.

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. For the HCC, HCC/BTC and BTC subgroups hepatitis C infection and hepatitis B infection if controlled with antiviral therapy are allowable.
2. Pregnancy or lactation.
3. Expected non-compliance.
4. 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.
5. 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.
6. 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 patient outcome in the setting of current cancer diagnosis.
7. Subjects who had been treated with ADI-PEG 20 previously.
8. History of seizure disorder not related to underlying cancer.
9. Known HIV positivity (testing not required).

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; Other Names: arginine deiminase formulated with polyethylene glycol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events.	Course of study.

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with objective responses.	Course of study.

Collaborators and Investigators

• Sponsor: Polaris Group

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: August 8, 2012
• First Submitted That Met QC Criteria: August 14, 2012
• First Posted (Estimate): August 15, 2012

Study Record Updates

• Last Update Posted (Estimate): February 25, 2016
• Last Update Submitted That Met QC Criteria: February 24, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: arginine; argininosuccinate synthetase; arginine deiminase
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: POLARIS2012-005