Clinical trial NCT00539591: Phase II Study Incorporating Pegylated Interferon In the Treatment For Children With High-Risk Melanoma
Official title: Phase II Study Incorporating Pegylated Interferon In the Treatment For Children With High-Risk Melanoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Malignant Melanoma
Keywords: Cutaneous Melanoma
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: Schering-Plough
First posted: 2007-10-04
Enrollment: 29
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main goal of this study is to estimate the tumor response rate of temozolomide administered in combination with peginterferon alfa-2b to pediatric patients with unresectable Stage III, metastatic, or recurrent cutaneous melanoma.

Detailed description: This study is for children with malignant melanoma and high risk features (at high risk of melanoma returning or spreading to other parts of the body) or who have recurrent disease. The study has two treatment groups based on the stage of the disease. Patients with stage IIC, IIIA or IIIB melanoma whose tumors have been removed by surgery will be treated in study group A. These patients will receive 4 weeks of high dose interferon alfa-2b followed by 48 weeks of peginterferon. Patients with stage IIIC or IV melanoma, stage III melanoma that could not be removed by surgery and those with recurrent disease will be treated in study group B. These patients will receive peginterferon alfa-2b and temozolomide.

Stratum A: Resected Stages IIC, IIIA, and IIIB patients

Induction therapy (weeks 1-4): Subjects will receive recombinant interferon alfa-2b 20 million units/m2 per day intravenously over 20-30 minutes on 5 consecutive days per week for 4 weeks. Subjects will receive peginterferon alfa-2b 1 mcg/kg/week subcutaneously for a total of 48 weeks.

Stratum B: Resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent patients

Stratum B is divided into 2 groups based on the presence (Stratum B1) or absence (Stratum B2) of measurable disease. Subjects will receive 8 weekly doses of peginterferon alfa-2b 0.5 mcg/kg/dose subcutaneously in combination with temozolomide 75mg/m2/dose by mouth daily for 6 weeks followed by 2 week break. The duration of each treatment course will be 8 weeks. Strata B2 (no measurable disease) will proceed with 7 courses as outlined.

Surgery interventions -Associated with both Strata A and B Surgery description: All subjects with initial presentation of melanoma (T1-4) will be treated with primary wide local excision with a minimum of 1cm margin (if anatomically feasible) surrounding the primary lesion or biopsy scar. For lesions with Breslow's thickness of \> 1mm or \<or= with ulceration or Clark's level IV/V, a 2 cm margin is preferred when anatomically feasible. Subjects with sentinel lymph node(s) positive for disease, will undergo complete lymph node dissection of the involved nodal basin.

Additional objectives include:

* To assess the safety of temozolomide administered in combination with peginterferon α-2b to pediatric patients with resected AJCC Stage IIIC, unresectable Stage III, metastatic, or recurrent cutaneous melanoma (Stratum B).
* To study the feasibility and safety of administering peginterferon α-2b weekly for 48 weeks following an initial induction phase with intravenous high dose interferon α-2b for 4 weeks to pediatric patients with resected thick melanomas (\> 4mm) with ulcerations (AJCC Stage IIC) and resected melanomas with regional lymph node metastases (AJCC Stage IIIA and IIIB) (Stratum A).

Eligibility criteria: Inclusion Criteria:

* AJCC stage IIC, III, IV or recurrent cutaneous melanoma
* Adequate bone marrow function
* Age less than or equal to 21 years of age at diagnosis
* Adequate liver and kidney function

Exclusion Criteria:

* Prior Therapy with dacarbazine or temozolomide
* Patients who have uncontrolled infection
* Patients with autoimmune hepatitis
* Patients who have a history of depression or other psychiatric diseases requiring hospitalization
* Patients taking systemic corticosteroids including oral steroids (i.e. prednisone, dexamethasone) or topical steroid creams/ointments. Steroid containing inhalers, steroid replacement for adrenal insufficiency and steroid premedication for prevention of transfusion or imaging contrast-agent related allergic reaction will be permitted.
* Patients with hypersensitivity reaction to non-pegylated interferon α-2b are not eligible for study
* Patients with diabetes mellitus not adequately controlled with medication
* Patients with hypo- or hyperthyroidism not adequately controlled with medication.
* Patients with a history of myocardial infarction, severe or unstable angina, or severe peripheral vascular disease.

Primary outcomes:
measure: Tumor Response Rate
timeFrame: 8 weeks
measure: Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Strata B1 and B2
timeFrame: 52 weeks
measure: Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Stratum A Patients
timeFrame: 52 weeks
measure: Probability of Event-free Survival (EFS) of Stratum A Participants
timeFrame: 3 years from diagnosis
Secondary outcomes:
Other outcomes:
measure: Median Steady State Trough Concentration of Pegylated Interferon ɑ-2B
timeFrame: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28
measure: Area Under the Curve (AUC) of Pegylated Interferon ɑ-2B
timeFrame: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28
measure: ɑ Half Life of Pegylated Interferon ɑ-2B
timeFrame: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28
measure: Volume of Central Compartment (Vc) of Pegylated Interferon ɑ-2B
timeFrame: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28
measure: Apparent Clearance (CL) of Pegylated Interferon ɑ-2B
timeFrame: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28
measure: Area Under the Curve (AUC) of Interferon ɑ-2b
timeFrame: Before first dose, and 1, 2, 4, 6, 8, 12, and 24 hours postinfusion
measure: Half-Life of Interferon ɑ-2b
timeFrame: Before first dose, and 1, 2, 4, 6, 8, 12, and 24 hours postinfusion
measure: Volume of Central Compartment (Vc) of Interferon ɑ-2b
timeFrame: Before first dose, and 1, 2, 4, 6, 8, 12, and 24 hours postinfusion
measure: Systemic Clearance (CL) of Interferon ɑ-2B
timeFrame: Before first dose, and 1, 2, 4, 6, 8, 12, and 24 hours postinfusion
measure: Mean Total PedsQL 4.0 Scores for Child Quality of Life (QoL) Assessments (Stratum A)
timeFrame: Pretherapy; Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
measure: Mean Total PedsQL 4.0 Scores for Child Quality of Life (QoL) Assessments (Stratum B)
timeFrame: Pretherapy; Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
measure: Mean Total PedsQL 4.0 Scores for Parent Quality of Life Assessments (Stratum A)
timeFrame: Pretherapy; Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
measure: Mean Total PedsQL 4.0 Scores for Parent Quality of Life Assessments (Stratum B)
timeFrame: Pretherapy; Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
measure: Mean Total PedsQL 3.0 Scores for Child Cancer Quality of Life (QoL) Assessments (Stratum A)
timeFrame: Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
measure: Mean Total PedsQL 3.0 Scores for Child Cancer Quality of Life (QoL) Assessments (Stratum B)
timeFrame: Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
measure: Mean Total PedsQL 3.0 Scores for Parent Cancer Quality of Life (QoL) Assessments (Stratum A)
timeFrame: Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
measure: Mean Total PedsQL 3.0 Scores for Parent Cancer Quality of Life (QoL) Assessments (Stratum B)
timeFrame: Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
measure: BASC-2 Psychological Assessment (Stratum A)
timeFrame: Pretherapy, Week 4, Week 24, End of Therapy, and 6 Months Post End of Therapy
measure: BASC-2 Psychological Assessment (Stratum B)
timeFrame: Pretherapy, Week 4, Week 24, End of Therapy, and 6 Months Post End of Therapy
measure: BRIEF Psychological Assessment (Stratum A)
timeFrame: Pretherapy, Week 4, Week 24, End of Therapy, and 6 Months Post End of Therapy
measure: BRIEF Psychological Assessment (Stratum B)
timeFrame: Pretherapy, Week 4, Week 24, End of Therapy, and 6 Months Post End of Therapy
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: The Children's Cancer Hospital at UT M.D. Anderson Cancer Center
state: Texas
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Alberto Pappo, MD
role: PRINCIPAL_INVESTIGATOR
References: