Melanoma (Skin)
Conditions
Keywords
recurrent melanoma, stage IV melanoma
Brief summary
RATIONALE: Peginterferon (PEG-interferon) alfa-2b may stop the growth of cancer by stopping blood flow to the tumor. PURPOSE: Phase II trial to study the effectiveness of PEG-interferon alfa-2b in treating patients who have stage IV melanoma.
Detailed description
OBJECTIVES: * Determine the ability of low-dose PEG-interferon alfa-2b to suppress plasma basic fibroblast growth factor (b-FGF) levels to normal in patients with metastatic melanoma over-expressing b-FGF. * Determine the antitumor effect of this drug, in terms of progression-free and overall survival and tumor response, in these patients. * Correlate tumor activity of this drug with b-FGF and vascular endothelial growth factor levels in the plasma and urine of these patients. * Determine the safety profile of this drug in these patients. OUTLINE: This is a multicenter study. Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 1 year. PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study within 2 years.
Interventions
BIOLOGICALPEG-interferon alfa-2b
Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed stage IV melanoma * Stage M1a, M1b, or M1c * Mucosal, ocular, or unknown primary melanoma * Previously untreated OR received up to 3 prior systemic therapy regimens (excluding vaccine therapy) for metastatic disease * Plasma basic fibroblast growth factor level at least 15 pg/mL * Measurable or evaluable disease * Central nervous system (CNS) involvement allowed provided CNS directed therapy has been given and disease has been clinically stable for ≥ 3 months * Brain computed tomography (CT) scan or Magnetic resonance imaging (MRI) to confirm stable disease required ≤ 4 weeks prior to study entry * Age: 18 and over * ECOG Performance status of 0-2 * Life expectancy at least 6 months * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Hemoglobin at least 8 g/dL (transfusions allowed) * Bilirubin no greater than 2 times upper limit of normal (ULN) * Alanine Aminotransferase (ALT) no greater than 2 times ULN * Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min * At least 4 weeks since prior interferon in the adjuvant or metastatic setting * At least 4 weeks since prior chemotherapy in the adjuvant or metastatic setting * At least 4 weeks since prior endocrine therapy in the adjuvant or metastatic setting * At least 4 weeks since prior radiotherapy in the adjuvant or metastatic setting * At least 4 weeks since prior surgery in the adjuvant or metastatic setting * At least 4 weeks since other prior therapy in the adjuvant or metastatic setting * Negative pregnancy test * Fertile patients must use effective contraception
Exclusion criteria
* Myocardial infarction within the past 6 months * Other active malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * Other concurrent illness that would preclude study participation * History of severe depression * Pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma b-FGF Level Response | assessed every 3 weeks until the suppression of plasma b-FGF level to normal, then every 6 weeks until the completion of 12 months of treatment, and upon treatment discontinuation | The primary endpoint was the suppression of plasma b-FGF level with low dose peginterferon alfa-2b. A clinically important reduction of plasma b-FGF levels was determined to be a level less than or equal to 7.5 pg/mL. A patient was considered to have a suppressed plasma b-FGF level, if the patient experienced the clinically significant reduction (less than or equal to 7.5 pg/mL) of plasma b-FGF levels for two consecutive determinations which were at least three weeks apart. This was considered as a b-FGF response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-progression Rate (Clinical Response to Peginterferon Alfa-2b) | assessed every 9 weeks until suppression of plasma b-FGF level to normal, every 12 weeks until the completion of 12 months of treatment, >= 4 weeks after documented response. After off treatment, every 3 months if <2 years, and every 6 months if 2-3 years | Objective tumor response was assessed using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria. Per RECIST criteria, complete response (CR) = disappearance of all target and non-target lesions. Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Progression is defined as at least 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing non-target lesions. Stable disease (SD) = did not meet criteria for response or progression. Non-progression rate = CR + PR + SD. |
| Progression Free Survival | assessed every 9 weeks until suppression of plasma b-FGF level to normal, every 12 weeks until the completion of 12 months of treatment, >= 4 weeks after documented response. After off treatment, every 3 months if <2 years, and every 6 months if 2-3 years | Progression free survival (PFS) was defined as the time from registration to disease progression, or censored at last known date of non progressive disease. |
| Overall Survival | assessed every 3 months if <2 years, and every 6 months if 2-3 years | Overall survival (OS) time was defined as the time from registration to death from any cause, or censored at last known date of survival. |
Countries
United States
Participant flow
Recruitment details
This study was activated on September 5, 2003, accrued its first patient on January 13, 2004, and patient accrual was terminated on June 15, 2011. A total of 32 patients were enrolled through ECOG member institutions. The study was suspended three times during the accrual period (February 2005, November 2006, January 2009) due to unavailability of ELISA kits to measure fibroblast growth factor.
Pre-assignment details
This study involves a pre-registration and a registration. In the pre-registration phase, plasma samples must be submitted for determinations of b-FGF status by central analysis. Only patients determined to have an elevated b-FGF level (\>15 pg/mL) by central review are eligible for registration.
Participants by arm
| Arm | Count |
|---|---|
| PEG-Interferon Alfa-2b Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 1 |
| Overall Study | ineligible | 3 |
| Overall Study | Lack of Efficacy | 25 |
| Overall Study | symptomatic deterioration | 1 |
Baseline characteristics
| Characteristic | PEG-Interferon Alfa-2b |
|---|---|
| Age, Continuous | 64 years |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 31 / 32 |
| serious Total, serious adverse events | 13 / 32 |
Outcome results
Primary
Plasma b-FGF Level Response
The primary endpoint was the suppression of plasma b-FGF level with low dose peginterferon alfa-2b. A clinically important reduction of plasma b-FGF levels was determined to be a level less than or equal to 7.5 pg/mL. A patient was considered to have a suppressed plasma b-FGF level, if the patient experienced the clinically significant reduction (less than or equal to 7.5 pg/mL) of plasma b-FGF levels for two consecutive determinations which were at least three weeks apart. This was considered as a b-FGF response.
Time frame: assessed every 3 weeks until the suppression of plasma b-FGF level to normal, then every 6 weeks until the completion of 12 months of treatment, and upon treatment discontinuation
Population: eligible and treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEG-interferon Alfa-2b | Plasma b-FGF Level Response | 34.5 percentage of participants |
Comparison: It is of interest to test the null hypothesis of 10% plasma b-FGF response rate versus the alternative hypothesis of 30% response rate. Based on the sample size of 30 eligible patients, there will be 84% power to detect this 20% difference in b-FGF response rates. This was based on a two-sided type I error of .05, using the one-sample binomial test.p-value: <0.001bionomial proportion test
Secondary
Non-progression Rate (Clinical Response to Peginterferon Alfa-2b)
Objective tumor response was assessed using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria. Per RECIST criteria, complete response (CR) = disappearance of all target and non-target lesions. Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Progression is defined as at least 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing non-target lesions. Stable disease (SD) = did not meet criteria for response or progression. Non-progression rate = CR + PR + SD.
Time frame: assessed every 9 weeks until suppression of plasma b-FGF level to normal, every 12 weeks until the completion of 12 months of treatment, >= 4 weeks after documented response. After off treatment, every 3 months if <2 years, and every 6 months if 2-3 years
Population: eligible and treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEG-interferon Alfa-2b | Non-progression Rate (Clinical Response to Peginterferon Alfa-2b) | 24.1 percentage of participants |
Secondary
Overall Survival
Overall survival (OS) time was defined as the time from registration to death from any cause, or censored at last known date of survival.
Time frame: assessed every 3 months if <2 years, and every 6 months if 2-3 years
Population: eligible and treated
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PEG-interferon Alfa-2b | Overall Survival | 9.7 months |
Secondary
Progression Free Survival
Progression free survival (PFS) was defined as the time from registration to disease progression, or censored at last known date of non progressive disease.
Time frame: assessed every 9 weeks until suppression of plasma b-FGF level to normal, every 12 weeks until the completion of 12 months of treatment, >= 4 weeks after documented response. After off treatment, every 3 months if <2 years, and every 6 months if 2-3 years
Population: eligible and treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PEG-interferon Alfa-2b | Progression Free Survival | 2 months |