Melanoma (Skin)
Conditions
Keywords
recurrent melanoma, stage IV melanoma
Brief summary
RATIONALE: Pegylated arginine deiminase may stop the growth of tumor cells by taking away an amino acid needed for cell growth. PURPOSE: This phase II trial is studying how well pegylated arginine deiminase works in treating patients with metastatic melanoma that cannot be removed by surgery.
Detailed description
OBJECTIVES: Primary: * Determine the clinical response (complete and partial response) in patients with unresectable metastatic melanoma treated with pegylated arginine deiminase. Secondary: * Determine the toxicity profile of this drug in these patients. * Determine the pharmacokinetics and pharmacodynamics of this drug in these patients. * Determine the progression-free survival and overall survival of patients treated with this drug. OUTLINE: Patients receive pegylated arginine deiminase intramuscularly once or twice a week in weeks 1-4. Courses repeat every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Blood samples are acquired at baseline and every 2 weeks thereafter for pharmacokinetic and pharmacodynamic studies. After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 5 years, and annually thereafter. PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.
Interventions
BIOLOGICALADI-PEG-20
There will be 6 cycles planned, each consisting of 4 weeks. During each cycle subjects will receive injections on days 1, 8, 15, and 22 + 2 days. All subjects may begin treatment with 160 IU/m2 on a weekly basis.
OTHERPharmacology Studies
tissue blocks will be obtained from the initial biopsy of melanoma. Immunohistochemical staining for ASS and RT-PCR will be performed on the tumor tissue
Sponsors
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed metastatic melanoma, meeting any of the following criteria: * Progressive disease after chemotherapy, radiotherapy, surgery, or immunotherapy * No longer responding to standard therapy OR have refused standard therapy * Unresectable disease * Measurable or evaluable disease * No clinical ascites * No symptomatic pleural effusion PATIENT CHARACTERISTICS: * Life expectancy ≥ 12 weeks * Karnofsky performance status 70-100% * Bilirubin ≤ 3.0 mg/dL * Albumin ≥ 3.0 g/dL * Alkaline phosphatase \< 5 times upper limit of normal (ULN) * Serum glucose \> 60 mg/dL * Amylase \< 1.5 times ULN * Absolute neutrophil count \> 1,500/mm³ * Platelet count \> 100,000/mm³ * No New York Heart Association class III-IV heart failure * No serious infection requiring treatment with antibiotics * No known allergy to E. coli drug products (e.g., sargramostim \[GM-CSF\]) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use 2 forms of effective contraception PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 4 weeks since prior anticancer therapy * At least 4 weeks since prior surgery and recovered * No concurrent participation in another investigational drug study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Partial and Complete Response) in Patients With or Without ASS Expression Present in Tumor. | Up to 16 months | Response rate is defined as a partial response, PR, and complete response, CR, lasting for at least 30 days per RECIST criteria, v. 1.0. Complete response will be defined as disappearance of all target lesions. Partial response will be defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference the baseline sum of LD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | Up to 16 months | Overall survival will be estimated using the product-limit method of Kaplan & Meier. |
| Median Time to Progression | Up to 16 months | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Single Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 25 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 69 years |
| Gender Female | 13 Participants |
| Gender Male | 25 Participants |
| Region of Enrollment United States | 38 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 37 |
| serious Total, serious adverse events | 9 / 37 |
Outcome results
Primary
Response Rate (Partial and Complete Response) in Patients With or Without ASS Expression Present in Tumor.
Response rate is defined as a partial response, PR, and complete response, CR, lasting for at least 30 days per RECIST criteria, v. 1.0. Complete response will be defined as disappearance of all target lesions. Partial response will be defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference the baseline sum of LD
Time frame: Up to 16 months
Population: Of the 38 subjects enrolled, only 10 were ASS-positive and 17 were ASS-negative. The remaining 11 subjects, who declined pre-treatment biopsies, were not assessed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADI-PED 20: Argininosuccinate Synthetase Positive (ASS+) | Response Rate (Partial and Complete Response) in Patients With or Without ASS Expression Present in Tumor. | 0 participants |
| ADI-PEG 20: Argininosuccinate Synthetase Negative (ASS-) | Response Rate (Partial and Complete Response) in Patients With or Without ASS Expression Present in Tumor. | 4 participants |
Secondary
Median Overall Survival
Overall survival will be estimated using the product-limit method of Kaplan & Meier.
Time frame: Up to 16 months
Population: Of the 38 subjects enrolled, only 10 were ASS-positive and 17 were ASS-negative. The remaining 11 subjects, who declined pre-treatment biopsies, were not assessed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ADI-PED 20: Argininosuccinate Synthetase Positive (ASS+) | Median Overall Survival | 9.3 months |
| ADI-PEG 20: Argininosuccinate Synthetase Negative (ASS-) | Median Overall Survival | 14.6 months |
Secondary
Median Time to Progression
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: Up to 16 months
Population: Of the 38 subjects enrolled, only 10 were ASS-positive and 17 were ASS-negative. The remaining 11 subjects, who declined pre-treatment biopsies, were not assessed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ADI-PED 20: Argininosuccinate Synthetase Positive (ASS+) | Median Time to Progression | 1.8 months |
| ADI-PEG 20: Argininosuccinate Synthetase Negative (ASS-) | Median Time to Progression | 3.6 months |