To prospectively assess the efficacy, toxicity, quality of life with peginterferon alfa-2b as compared to observation after adequate surgery for ulcerated primary cutaneous melanomas with T(2-4)bN0M0
ID
Source
Brief title
Condition
- Skin neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
Relapse-free survival (RFS) will be assessed by physical, US/CT/MRI and /or
biopsy
Secondary outcome
Secondary endpoints:
Overall survival (OS)
Distant metastases-free survival (DMFS) will be assessed by imaging and/or
biopsy
Quality of life will be assessed by QLQ-C30 version 3
Background summary
The main purpose of this study is to determine whether post-operative adjuvant
therapy for two years with Peginterferon alfa-2b improves relapse-free survival
(RFS) as compared to observation (no treatment will be given for your cancer).
The other objectives are to assess safety, distant metastasis free survival,
overall survival and quality of life.
It has been shown in some previous studies that patients who have ulcerated
melanoma tend to relapse faster when compared to their non ulcerated
counterparts and this also reflected in the overall survival of the patients.
The biological characteristics of ulcerated cancers are quite different in that
their immune response is different and moreover it has been demonstrated that
lymph nodes of these melanomas have much more suppressed immune cell counts
along with different white blood cell populations.
Interferon * has been the most studied drug in the adjuvant setting and has
been evaluated in a number of trials and is the most promising agent at
present. peginterferon alfa-2b is pegylated interferon in which the PEG
(polyethylene glycol) protects the interferon from faster breakdown in the body
thereby increasing the time the drug stays in the body. This essentially means
that less amount peginterferon alfa-2b will have the same benefit as compared
to high dose normal interferon.
peginterferon alfa-2b is approved by US Food and Drug Administration to treat
patients of melanoma whose cancer has been removed surgically but their lymph
nodes have been invaded by melanoma. This above mentioned approval was given
based on a study conducted by EORTC.
Study objective
To prospectively assess the efficacy, toxicity, quality of life with
peginterferon alfa-2b as compared to observation after adequate surgery for
ulcerated primary cutaneous melanomas with T(2-4)bN0M0
Study design
This is a multicenter randomized phase III trial.
A total of 1200 patients with ulcerated primary cutaneous melanoma T(2-4)b N0M0
will be randomized within 12 weeks after definitive surgery into two
equal-sized arms (approximately 600 patients each):
ARM A: Peginterferon alfa-2b subcutaneous injection at 3.0 *g/kg, weekly for 2
years or until relapse of disease.
ARM B: OBSERVATION
Treatment will be administered unless there is relapse of the disease,
unacceptable toxicity, patient's refusal, patient's best interest to stop
according to treating physician.
Intervention
Peginterferon alfa-2b is administered by subcutaneous injection at a dose of
3.0 *g/kg.
Acetaminophen (500-1000 mg) will be given in the clinic 30 minutes prior to
receiving the first dose of peginterferon alfa-2b. Subjects should be observed
for 1-2 hours after the first dose. Acetaminophen (500-650 mg PO q 4-6 hours)
should be continued as needed, and should not exceed 3000 mg/day.
Patients who are deemed competent to self administer the subcutaneous
injections of peginterferon alfa-2b will be instructed and may do so.
Patients in ARM A:Peginterferon alfa-2b will receive peginterferon alfa-2b (3.0
*g/kg), weekly for 2 years or until relapse of the disease, unacceptable
toxicity, patient's refusal, patient's best interest to stop according to
treating physician.
Study burden and risks
Patients may have side effects while on the study.
Side effects may be mild or very serious. Many side effects go away soon after
taking the peginterferon alfa-2b. In some cases, side effects can be serious,
long lasting, or may never go away.
Risks and side effects related to the peginterferon alfa-2b include those which
are:
Likely
* Fatigue
* Loss of appetite, weight loss, taste alterations
* Depression
Less Likely
* Flu-like symptoms: Fever, chills, rigors
* Muscle aches, joint aches, headaches
* Nausea, vomiting, diarrhea
* Increase in heart rate (less common: irregular heartbeat)
* Mood alterations
* Rash (localized at injection site or diffuse)
* Abnormality in liver enzymes and bilirubin
* Alteration in kidney function (rare: kidney failure)
* Alteration in blood counts
Reproductive risks: Patients should not become pregnant or father a baby while
on this study because the drugs in this study can affect an unborn baby. Women
should not breastfeed a baby while on this study. Patients need to use birth
control while on this study.
Avenue Mounierlaan 83/11
BRUSSELS 1200
NL
Avenue Mounierlaan 83/11
BRUSSELS 1200
NL
Listed location countries
Age
Inclusion criteria
- Subjects must have histologically documented ulcerated primary cutaneous melanoma with a Breslow thickness of more than 1mm that has been excised radically 3 months prior to randomization. Excision margins of at least 1 cm are required. In the head and neck areas and in case of locations distally on extremities narrower margins are acceptable as long as they are radical.;Subjects must undergo Sentinel Node staging after the excision of the primary, and this must be done within the time frame of 3 months between the date of final excision of the primary and the date of randomization.;- Subjects must have an ECOG performance status of 0 or 1.;- Subjects must be between 18-70 years old.;- Subjects must have adequate hepatic, renal and bone marrow function as defined by the following parameters obtained within 120 hours prior to initiation of study treatment;- Subject must give informed consent according to ICH-GCP or national/local policy
Exclusion criteria
- Subjects suffering from a mucous membrane melanoma or ocular melanoma;- Subjects who have evidence of (non-)regional lymph node metastases or intransit metastases (even if they have been resected);- Subjects whose disease cannot be completely surgically resected;- Subjects who have not recovered from the effects of recent surgery;- Subjects with a history of prior malignancy within the past 5 years other than surgically cured non-melanoma skin cancer or cervical carcinoma in situ;- Subjects who have severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease;- Subjects with thyroid dysfunction not responsive to therapy;- Subjects with uncontrolled diabetes mellitus;- Subjects suffering from an active autoimmune disease;- Subjects with active and/or uncontrolled infection, including active hepatitis;- Subjects who have a history of seropositivity for HIV;- Subjects who have a history of neuropsychiatric disorder requiring hospitalization;- Subjects who are known to be actively abusing alcohol or drugs;- Subjects who are pregnant, lactating, or of reproductive potential and not practicing an effective means of contraception;- Subjects with a medical condition requiring chronic systemic corticosteroids;- Subjects who have received any experimental therapy within 30 days prior to randomization in this study;- Subjects who have received any prior chemotherapy, immunotherapy, hormonal or radiation therapy for melanoma;- Subjects who have previously received interferon-alpha for any reason;- Subject having history of epilepsy or other major central nervous system disease;- Subject having eyes disorders
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-010273-20-NL |
| ClinicalTrials.gov | NCT01502696 |
| CCMO | NL42514.078.12 |