Phase II Study Incorporating Pegylated Interferon In the Treatment For Children With High-Risk Melanoma

NCT00539591 | Active Not Recruiting Phase 2 Results

• 2 other identifiers: MEL06NCI-2011-01192
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

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.

Conditions

Malignant Melanoma

Keywords

Cutaneous Melanoma

Outcome Measures

Primary Outcomes (4)

• Tumor Response Rate

  Tumor response rate of stratum B1 participants was evaluated after 1 treatment course of temozolomide plus peginterferon ɑ-2b. Complete response (CR) and partial response (PR) confirmed with repeated scan at least 4 weeks apart following completion of course 1 therapy. CR defined as disappearance of all target and non-target lesions with no new lesions detected. If available, no disease must be detected by immunocytology or serum tumor markers. PR defined as at least 30% decrease in disease measurement compared to disease measurement at study entry with no new lesions detected. Progressive disease (PD) defined as at least 20% increase in the disease measurement compared to the smallest disease measurement recorded since start of treatment, or appearance of one or more new lesions. Stable disease defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD compared to smallest disease measurement since start of treatment.

  8 weeks

• Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Strata B1 and B2

  The objective was to assess the safety of temozolomide administered in combination with peginterferon a-2b in Stratum B participants. Accrual was suspended any time during therapy if 2 or more of 6, 4 or more of 12, 6 or more of 18, 8 or more of 24, 10 or more of 30 participants experienced target toxicity defined as: * Grade 4 non-hematologic (non-hem) toxicity that does not resolve to ≤grade 1 within 2 weeks from the time next dose is due and is determined to be probably or definitely related to protocol therapy * Grade 4 non-hem toxicity that is NOT constitutional symptoms (fever, chills, fatigue and/or pain) * Grade 3 elevations in creatinine or BUN that are determined to be probably or definitely related to protocol therapy * Grade 4 cardiopulmonary toxicity that is determined to be probably or definitely related to protocol therapy * Grade 4 mood alteration (suicidal ideation; danger to self or others)

  52 weeks

• Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Stratum A Patients

  The objective was to study the feasibility and safety of administering peginterferon a-2b weekly for 48 weeks following the initial induction phase to Stratum A participants. Accrual was suspended during the 48-week course if 2 or more of 6, 4 or more of 12, 6 or more of 18, 8 or more of 24, 10 or more of 30 participants experienced target toxicity defined as: * Grade 4 non-hematologic (non-hem) toxicity that does not resolve to ≤grade 1 within 2 weeks from the time next dose is due and is determined to be probably or definitely related to protocol therapy * Grade 4 non-hem toxicity that is NOT constitutional symptoms (fever, chills, fatigue and/or pain) * Grade 3 elevations in creatinine or BUN that are determined to be probably or definitely related to protocol therapy * Grade 4 cardiopulmonary toxicity that is determined to be probably or definitely related to protocol therapy * Grade 4 mood alteration (suicidal ideation; danger to self or others)

  52 weeks

• Probability of Event-free Survival (EFS) of Stratum A Participants

  The probability of EFS was estimated as time to first event (relapse, death or second malignancy). As of April 2016, 21 out of 23 participants had no events. The EFS rate was estimated by Kaplan-Meier method.

  3 years from diagnosis

Other Outcomes (21)

• Median Steady State Trough Concentration of Pegylated Interferon ɑ-2B

  Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28

• Area Under the Curve (AUC) of Pegylated Interferon ɑ-2B

  Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28

• ɑ Half Life of Pegylated Interferon ɑ-2B

  Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28

Study Arms (2)

Temozolomide/peginterferon alfa-2b

EXPERIMENTAL

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 (SQ) in combination with temozolomide 75mg/m2/dose by mouth (PO) 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.

Drug: Peginterferon alfa-2b; Drug: Temozolomide

Peginterferon alfa-2b/non-pegylated interferon alfa-2b

EXPERIMENTAL

Stratum A: Resected Stages IIC, IIIA, and IIIB patients will receive recombinant interferon alfa-2b 20 million units/m2/day intravenously (IV) 5 consecutive days per week for 4 weeks followed by peginterferon alfa-2b 1mcg/kg subcutaneously (SQ) once a week for 48 weeks.

Drug: Peginterferon alfa-2b; Drug: Temozolomide; Drug: Recombinant interferon alfa-2b

Interventions

Peginterferon alfa-2b DRUG

Given either IV or SQ. Therapeutic drug class: interferon.

Also known as: PEG-Intron(R), pegylated interferon alfa-2b

Peginterferon alfa-2b/non-pegylated interferon alfa-2b; Temozolomide/peginterferon alfa-2b

Temozolomide DRUG

Given PO. Therapeutic drug class: antineoplastic agent.

Also known as: Temodar(R), SCH 52365

Peginterferon alfa-2b/non-pegylated interferon alfa-2b; Temozolomide/peginterferon alfa-2b

Recombinant interferon alfa-2b DRUG

Given IV. Therapeutic drug classes: antineoplastic agent, immunomodulatory agent, interferon

Also known as: Intron®, non-pegylated interferon alfa-2b

Peginterferon alfa-2b/non-pegylated interferon alfa-2b

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Schering-Plough: collaborator

Study Sites (3)

Rady Children's Hospital

San Diego, California, 92123, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

The Children's Cancer Hospital at UT M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Melanoma

Interventions

peginterferon alfa-2b; Temozolomide; Introns

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes

Limitations and Caveats

The study closed early due to poor accrual to stratum B1.

Results Point of Contact

• Title: Alberto Pappo, MD
• Organization: St. Jude Children's Research Hospital

info@stjude.org

901-595-2322

Study Officials

• Alberto Pappo, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2007
• First Posted: October 4, 2007
• Study Start: May 9, 2008
• Primary Completion: June 1, 2015
• Study Completion: May 1, 2026
• Last Updated: December 23, 2025
• Results First Posted: February 27, 2014

Record last verified: 2025-12

Locations

US (3)