Melanoma
Conditions
Brief summary
This is a Phase II/III randomized, controlled, multicenter, open-label study designed to assess the safety, efficacy, and impact on quality of life of PEG Intron (MK-4031) and INTRON® A (MK-2958) and the pharmacokinetics of PEG Intron when given as adjuvant (after surgery) therapy in participants with resected (surgically removed) Stage III node-positive cutaneous melanoma.
Detailed description
This study was closed to enrollment prematurely due to sub-optimal accrual. Participants who were enrolled prior to enrollment closure were allowed to continue to receive study drug; these participants were followed for safety only.
Interventions
BIOLOGICALPEG-Intron
Polyethylene glycol (PEG)12000 Interferon alfa 2-b subcutaneous injection.
BIOLOGICALINTRON A
Interferon alfa-2b, recombinant for intravenous injection.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Participants must have histologically documented primary cutaneous melanoma meeting one of the following staging criteria: * Primary melanoma of any stage in the presence of N1 regional lymph node metastases detected at elective lymph node dissection or sentinel node biopsy, with clinically inapparent regional lymph node metastasis (any pTN1M0). * Clinically apparent N1 or N2a regional lymph node involvement synchronous with primary melanoma of T1-4 (any pTN1-2aM0). * Regional lymph node recurrence at any interval after appropriate surgery for primary melanoma of any depth (any primary tumor \[pT\], r N1-2a M0). * Participants must have had all known disease completely resected with adequate surgical margins within 56 days prior to randomization into the study * Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Participants must have adequate hepatic, renal and bone marrow function as defined by the following parameters obtained within 14 days prior to initiation of study treatment: * Hematology: white blood cells (WBC) ≥3,000 cells/µL and hemoglobin ≥9 g/dL. * Renal and hepatic function: serum creatinine \<2.0 mg/dL; aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) \<2 times upper limit of laboratory normal (ULN); and serum bilirubin \<2 times ULN * Participants must sign and date a voluntary informed consent form before study entry, be willing to participate in this study and agree to complete all follow-up assessments.
Exclusion criteria
* Participants who have received any prior chemotherapy, immunotherapy hormonal or radiation therapy for melanoma. * Participants who have evidence of distant or non-regional lymph node metastases, in-transit metastases, or positive lymph nodes with an unknown primary. * Participants whose disease cannot be completely surgically resected because of gross extracapsular extension. * Participants who have previously received interferon for any reason. * Participants who have severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure (New York Heart Association \[NYHA\] Class III or IV) or symptomatic ischemic heart disease. * Participants who have a history of neuropsychiatric disorder requiring hospitalization. * Participants with thyroid dysfunction not responsive to therapy. * Participants with uncontrolled diabetes mellitus. * Participants with a history of prior malignancy within the past 5 years other than surgically cured non-melanoma skin cancer or cervical carcinoma in situ. * Participants who have a history of seropositivity for human immunodeficiency virus (HIV). * Participants who are pregnant, lactating, or of reproductive potential and not practicing an effective means of contraception. * Participants with active and/or uncontrolled infection, including active hepatitis. * Participants with a medical condition requiring chronic systemic corticosteroids. * Participants who are known to be actively abusing alcohol or drugs. * Participants who have received any experimental therapy within 30 days prior to randomization in this study. * Participants who have not recovered from the effects of recent surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | From time of randomization to time of progression or death (up to approximately 26 months) | Progression-free survival time was defined as the time from the date of randomization to the date of disease progression or the date of death regardless of the cause. PFS was to be assessed by clinical observation, with recurrence documented by appropriate radiographic and histologic methods, and confirmed by Independent Central Review. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From time of randomization to time of death (up to approximately 26 months) | Overall survival (OS) is the time from randomization to death due to any cause. Participants were to be followed for survival every 3 months. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. After the early termination of the study, participants were followed for safety only. Although the OS analysis is not in the clinical study report due to early termination of the study, an OS ad hoc analysis was requested by the FDA and is therefore presented in this outcome measure. Below table presents the median duration of survival for participants. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PEG-Intron Participants with stage III node positive cutaneous melanoma received subcutaneous PEG-Intron (6.0 ug/kg weekly) for up to 24 months post-surgery | 63 |
| INTRON A Participants with stage III node positive cutaneous melanoma received intravenous INTRON A (20 million international units \[MIU\]/m\^2/day, 5 days a week) for 4 weeks followed by subcutaneous INTRON A (10 MIU/m\^2 three times per week) for up to 12 months post-surgery | 63 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 0 | 14 |
| Overall Study | Adverse event in first 12 months | 12 | 8 |
| Overall Study | Did not complete study treatment | 2 | 3 |
| Overall Study | Did not meet eligibility criteria | 1 | 0 |
| Overall Study | Disease progression | 25 | 17 |
| Overall Study | Not in participant's best interest | 2 | 1 |
| Overall Study | Unknown (no reason provided) | 4 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 7 |
Baseline characteristics
| Characteristic | PEG-Intron | INTRON A | Total |
|---|---|---|---|
| Age, Continuous | 48.1 Years STANDARD_DEVIATION 13.6 | 49.2 Years STANDARD_DEVIATION 12.2 | 48.6 Years STANDARD_DEVIATION 12.9 |
| Sex: Female, Male Female | 24 Participants | 22 Participants | 46 Participants |
| Sex: Female, Male Male | 39 Participants | 41 Participants | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 63 | 9 / 63 |
| other Total, other adverse events | 61 / 63 | 60 / 63 |
| serious Total, serious adverse events | 24 / 63 | 19 / 63 |
Outcome results
Primary
Progression-free Survival (PFS)
Progression-free survival time was defined as the time from the date of randomization to the date of disease progression or the date of death regardless of the cause. PFS was to be assessed by clinical observation, with recurrence documented by appropriate radiographic and histologic methods, and confirmed by Independent Central Review.
Time frame: From time of randomization to time of progression or death (up to approximately 26 months)
Population: All randomized participants. Due to the early termination of this study, confirmation of PFS by Independent Central Review was not collected and; therefore, PFS could not be analyzed as planned per protocol.
Secondary
Overall Survival
Overall survival (OS) is the time from randomization to death due to any cause. Participants were to be followed for survival every 3 months. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. After the early termination of the study, participants were followed for safety only. Although the OS analysis is not in the clinical study report due to early termination of the study, an OS ad hoc analysis was requested by the FDA and is therefore presented in this outcome measure. Below table presents the median duration of survival for participants.
Time frame: From time of randomization to time of death (up to approximately 26 months)
Population: All treated participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PEG-Intron | Overall Survival | NA Months |
| INTRON A | Overall Survival | 23.72 Months |
95% CI: [0.28, 1.77]