High-Dose PEG-Intron Pharmacokinetic Study in Patients With Melanoma (Study P04831 AM2)

A Pharmacokinetic Study of PEG-Intron, Administered Weekly in Subjects With High-Risk Melanoma

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00457418

Enrollment

Registered

2007-04-06

Start date

2007-02-20

Completion date

2012-07-11

Last updated

2017-06-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Melanoma

Brief summary

The purpose of this study is to establish the pharmacokinetics of PEG-Intron, administered at a dose of 6 μg/kg/week for 8 weeks (induction treatment), followed by a dose of 3 μg/kg/week for up to 252 weeks (maintenance treatment), in patients with high risk melanoma.

Interventions

DRUGPEG-Intron

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Subjects at least 18 years of age, of either sex, and of any race. * Cytologically or histologically-confirmed melanoma, arising from a cutaneous or unknown site of origin, at Stages IIB, IIC, IIIA, IIIB, IIIC according to the American Joint Committee on Cancer (AJCC) 2001 guidelines. * Adequate hepatic, renal and bone marrow function within 4 weeks prior to initiation of study treatment. * Subjects presenting with synchronous primary and regional melanoma must have had adequate surgical margins surrounding the primary lesion. * Full lymphadenectomy must be performed within 90 days prior to initiation of study treatment. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Give informed consent according to International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) and national/local policy. * Be able to adhere to dose and visit schedules. * Female subjects of childbearing potential must be using a medically accepted method of birth control prior to Screening and agree to continue its use during the study or be surgically sterilized. * Female subjects of childbearing potential must have a negative serum pregnancy test at Screening.

Exclusion criteria

* Female subjects who are pregnant, intend to become pregnant, or are breastfeeding. * Previous treatment with interferon alpha, chemotherapy or immunotherapy for melanoma. * Ocular melanoma, or melanoma of the mucous membranes. * Evidence of distant or non-regional lymph node metastases. * In-transit melanoma, even if the lesion has been resected. * Disease that cannot be completely surgically resected. * Lack of recovery from recent surgery. * Prior malignancy within the past 5 years, except surgically cured squamous cell carcinoma of the skin, successfully resected early stage cutaneous melanoma, or cervical carcinoma in situ. * Severe cardiovascular disease. * Thyroid dysfunction not responsive to therapy. * Uncontrolled diabetes mellitus (in the opinion of the investigator). * Active autoimmune disease. * Active and/or uncontrolled infection. * History of seropositivity for human immunodeficiency virus (HIV). * Pre-existing psychiatric condition. * Clinical diagnosis of substance abuse of one or more of the following drugs within the following timeframes (excluding time spent in detoxification, hospitalization or incarceration): * Alcohol, intravenous drug use, inhalational, psychotropics, narcotics, cocaine, prescription or over-the-counter drugs: within 1 year of the Screening visit. * Methadone, buprenorphine hydrochloride (HCl), and/or butorphanol tartrate: within 1 year of Screening visit, unless subject has drug screen negative for other (non-narcotic) drugs documented in the past year and repeated negative within 2 months of Screening visit. * Multi-drug abuse (2 or more substances in 16a and 16b): within 3 years of Screening visit. * Marijuana: * If historic use is deemed excessive by the principal investigator (or medically qualified individual), or is interfering with the subject's life, then the subject is not eligible and should not be screened. * If marijuana use is not deemed excessive by principal investigator and does not interfere with life, subject must discontinue any current use of marijuana prior to entry into study. * Medical condition requiring chronic systemic corticosteroids. * Known allergy to the drug substance or any of the excipients in the PEG-Intron formulation. * Any situation or condition that, in the opinion of the investigator, may interfere with optimal participation in the study. * Use of any investigational drugs within 30 days of study entry. * Participation in other clinical studies of investigational treatments.

Design outcomes

Primary

Measure	Time frame	Description
Average Concentration Within the Dosing Interval (Cavg) of PEG-Intron at 12 Weeks	Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeks	Cavg was defined as average plasma concentration.
Area Under the Curve (AUC) of PEG-Intron at 12 Weeks	Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeks	AUC was defined as the actual body exposure to drug after administration of a dose of the drug.
Maximum Serum Concentration (Cmax) of PEG-Intron at 12 Weeks	Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeks	Cmax was defined as observed maximum plasma concentration.
Apparent Clearance(CL/F) of PEG-Intron at 12 Weeks	Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeks	CL/F was defined apparent clearance - the volume of plasma in the vascular compartment cleared of drug per unit of time and per kilogram of body weight by the processes of metabolism and excretion.
Minimum Serum Concentration (Cmin) of PEG-Intron at 12 Weeks	Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeks	Cmin was defined as observed minimum plasma concentration.
Observed Time to Achieve Cmax (Tmax) of PEG-Intron at 12 Weeks	Predose, and 24, 48, 72, 96, and 168 hours postdose at 12 weeks	Tmax was defined as time of maximum plasma concentration.

Secondary

Measure	Time frame	Description
Number of Participants Who Experienced an Adverse Event (AE)	Entire study duration (up to 5 years)	An adverse event (AE) was defined as any untoward medical occurrence or unfavorable and unintended sign in a subject administered a pharmaceutical product, biologic (at any dose), or medical device, whether or not considered related to the use of that product.

Participant flow

Participants by arm

Arm	Count
PEG-Intron 6 ug/kg/week, SC (first 8 weeks) 3 ug/kg/week, SC (252 weeks \[weeks 9-260\], maintenance)	32
Total	32

Withdrawals & dropouts

Period	Reason	FG000
Pharmacokinetic (PK) Sampling Phase	Adverse Event	2
Pharmacokinetic (PK) Sampling Phase	Non-compliance with protocol	2
Pharmacokinetic (PK) Sampling Phase	Progression of Disease	1
Post PK Maintenance	Adverse Event	10
Post PK Maintenance	Lost to Follow-up	1
Post PK Maintenance	Progression of Disease	6
Post PK Maintenance	Withdrawal by Subject	11

Baseline characteristics

Characteristic	PEG-Intron
Age, Continuous	49.1 years STANDARD_DEVIATION 12.8
Sex: Female, Male Female	10 Participants
Sex: Female, Male Male	22 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	32 / 32
serious Total, serious adverse events	9 / 32

Outcome results

Primary

Apparent Clearance(CL/F) of PEG-Intron at 12 Weeks

CL/F was defined apparent clearance - the volume of plasma in the vascular compartment cleared of drug per unit of time and per kilogram of body weight by the processes of metabolism and excretion.