Clinical Trial Result Information
Title of Study:
Phase II Randomized Dose-Finding Study of Subcutaneous Administration of Three Different Doses of Pegylated Interferon alfa-2a in Patients With Metastatic Malignant Melanoma (MM).
Fast Facts:
| Protocol number: | NO16007 |
| Sponsor: | Hoffmann-La Roche Inc |
| Company division: | Pharmaceutical |
| Product name: | PEGASYS |
| Generic name: | peginterferon alfa-2a (40KD) |
| Phase of development: | II |
| Therapeutic area, approved indication: | Malignant Melanoma |
| Date of report: | 10/1/2007 |
Clinical study summary:
This was an open-label, randomized, multicenter, dose finding study to evaluate the efficacy and safety of PEGASYS (pegylated interferon alfa-2a (40KD)) in patients with metastatic malignant melanoma. Evaluable patients with Stage IV melanoma were randomized to one of 3 dose groups (180μg, 360μg, 450μg). The planned treatment period was 24 weeks; however, if the patient did not have evidence of progressive disease at the end of a 24-week period, the patient could continue therapy up to the point of progressive disease (PD), at the discretion of the investigator and sponsor. In case of complete response, the patient could continue therapy for at least another 8 weeks.
Study center(s) :
33 centers in Austria, Canada, France, Germany, Italy, Netherlands, Spain, Switzerland, UK and USA.
Objectives:
To evaluate the tolerability, safety and efficacy of 3 doses of PEGASYS administered subcutaneously (sc) once weekly in patients with cutaneous metastatic melanoma (Stage IV, AJCC).
Methodology:
Patients were scheduled to have 24 weeks treatment, plus a treatment extension period for responders. They had weekly assessments for the first 4 weeks, followed by monthly assessments. Disease response was assessed by x-ray, CT-scans and/or MRI. Pharmacokinetics, pharmacodynamics and Quality of Life assessments were made at intervals throughout the study. Survival follow-up assessments, concomitant therapy documentation and post study anti-cancer treatment was collected every 3 months after a patient prematurely withdrew or completed the acute treatment phase or completed the maintenance treatment phase.
Number of patients (planned/analyzed):
Planned: 135 patients. Enrolled: 150 patients.
Diagnosis and main criteria for inclusion:
Male or female ≥18 and ≤75 years old.
Outpatients with cutaneous metastatic melanoma (Stage IV, AJCC) with documented primary skin lesion and distant metastases.
Test product, dose and mode of administration or test procedure:
PEGASYS (peginterferon alfa-2a (40KD)), sc once weekly, (180μg, 360μg, 450μg).
Duration of treatment:
24 weeks
Reference therapy, dose and mode of administration or reference procedure:
N/A.
Criteria for evaluation (efficacy, safety):
Efficacy: Measurements of visible and palpable tumor: chest x-rays, CT-scans and/or MRI.
Pharmacodynamics: Neopterin, 2',5' -oligoadenylate synthetase (2',5' -OAS), S-100 B, melanoma inhibitory activity (MIA).
Pharmacokinetics: Cmax, Tmax, t1/2, AUC of peginterferon alfa-2a (40KD) in selected patients; and trough (Cmin) levels of peginterferon alfa-2a (40KD) in all patients.
Tolerability/Safety: Frequency of dose reduction, incidence of adverse events, incidence of abnormal laboratory test results.
Statistical methods:
An administrative analysis was performed after 90 patients (30 per group) had completed 24 weeks of the study by completing 24 weeks of treatment, prematurely withdrawing or having died prior to 24 weeks in the study.
All tolerability and safety data were summarized using descriptive statistics for each dose group. To evaluate the maximum tolerated dose, the number of patients who did not tolerate the assigned dose (i.e. those who had dose reduction or temporary hold for AE or lab abnormalities) was summarized.
Incidence of the tumor response (CR or PR) during 24 weeks of treatment and incidence of death at 6 months and one year was summarized along with the 95% confidence interval for each dose group, The time to response, progression, and death was summarized based on the Kaplan-Meier estimates for each dose group.
Summary (efficacy, safety, other results):
Efficacy: There was no significant difference in tumor response rates and survival between treatment groups. The median (range) duration of overall survival was 217.5 (153-338) days, 319.0 (192-486) days, and 322.0 (234-660) days, in the low, middle, and high-dose groups, respectively.
Safety: The majority of dose adjustments were due to AEs or laboratory abnormalities, and occurred within the first 3 months of treatment. Dose hold and/or reduction for adverse events (AEs) or laboratory abnormalities was required for 22.9%, 50.9% and 40.8% of patients in the low, middle and high-dose groups, respectively.
During the 24-week treatment phase of the study, the most commonly reported AEs acorss all treatment groups were, in the low, middle and high-dose treatment groups, respectively: fatigue 52%, 57% and 59%; pyrexia 44%, 43% and 47%; nausea 42%, 34% and 37%; anorexia 21%, 21% and 39%; rigors 29%, 32% and 18%; and headache 17%, 26% and 33%. The results during the entire study period were similar. In all 3 treatment groups, approximately half of the AEs were mild in intensity.
A total of 130 patients died during the study; 46/47 in the low dose group, 46/53 in the middle-dose group and 38/49 in the high dose group. Most patients died from their malignant melanoma.
Conclusions:
The tolerability, efficacy and safety of all three dose groups were comparable, with no apparent dose-related effect.
Click here for the protocol registry listing of this trial.
