Clinical trial NCT01528384: Ph 1 Study of ADI PEG 20 in Pediatric Subjects Who Are Argininosuccinate Synthetase (ASS) Deficient
Official title: A Phase 1 Study of ADI PEG 20 in Pediatric Subjects Who Are Argininosuccinate Synthetase (ASS) Deficient and Have Failed Prior Systemic Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Argininosuccinate Synthetase Deficient
Keywords: Arginine
Arginine deiminase
Argininosuccinate synthetase
Phase 1
Pediatric
Failed other treatments
Pediatric patients
Lead sponsor: Polaris Group
Sponsor class: INDUSTRY
First posted: 2012-02-08
Enrollment: 8
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase 1 study of pegylated arginine deiminase (ADI-PEG 20) in pediatric patients who deficient in the expression of tumor argininosuccinate synthetase, and have failed prior treatments. The study hypothesis is that this drug will be safe in pediatric patients.

Detailed description: This phase 1 study will use a classic 3 dose levels by 3 patients per dose level design. Once the maximum tolerated dose is reached, additional patients may be enrolled at that dose level.

Eligibility criteria: Inclusion Criteria:

1. Prior diagnosis of failed current standard treatment(s), or AEs associated with prior systemic agent(s) that resulted in discontinuance of that agent(s).
2. Argininosuccinate synthetase deficient tumor.
3. Measurable disease as assessed by \>5% blasts on bone marrow aspirate for patients with leukemia or using RECIST 1.1 criteria for solid tumors.
4. Age 4 to ≤ 18 years.
5. No prior systemic treatment for the tumor in the last 2 weeks for solid tumors and 1 week for leukemia, except hydroxyurea used only to control very high WBC.
6. Fully recovered from any prior surgery and no major surgery within 4 weeks of initiating treatment. Surgery for placement of vascular access devices is acceptable.
7. Female subjects of 10 years and older and male subjects must be asked to use appropriate contraception for both the male and female for the duration of the study.
8. No concurrent investigational studies are allowed.
9. For solid tumor subjects only: Absolute neutrophil count (ANC) \>750/µL.
10. For solid tumor subjects only: Platelets \>50,000/µL.
11. For solid tumor subjects only: Serum uric acid ≤ 8 mg/dL (with or without medication control).
12. Serum creatinine ≤ 1.5 x the upper limit of normal range, or, if serum creatinine \>1.5 x the upper limit of normal range, then the creatinine clearance must be ≥ 60 mL/min.

Exclusion Criteria:

1. Serious infection requiring treatment with systemically administered antibiotics at the time of study entrance.
2. Pregnancy or lactation.
3. Expected non-compliance.
4. Uncontrolled intercurrent illness.
5. Subjects who have had any anticancer treatment prior to entering the study and have not recovered to baseline or ≤ Grade 1 AEs due to agents administered.
6. Subjects who had been treated with ADI-PEG 20 previously.
7. History of seizure disorder not related to underlying cancer.
8. Known HIV positivity.

Primary outcomes:
measure: Change in laboratory values.
timeFrame: 2 years
Secondary outcomes:
measure: Results of diagnostic imaging using RECIST criteria.
timeFrame: 2 years
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Cynthia Herzog, MD
role: PRINCIPAL_INVESTIGATOR
References: