Temozolomide + Peginterferon for Melanoma

Recruiting at 2 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Corticosteroids

Disqualifiers: Uncontrolled infection, Autoimmune hepatitis, Depression, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic corticosteroids, including oral steroids like prednisone and dexamethasone, as well as topical steroid creams or ointments. However, steroid inhalers, steroid replacement for adrenal insufficiency, and steroid premedication for allergic reactions are allowed.

Is the combination of Temozolomide and Peginterferon safe for humans?

Research shows that Temozolomide combined with Peginterferon has been studied for safety in patients with melanoma and other tumors. These studies generally focus on understanding the safety profile, which includes monitoring for side effects and determining safe dosage levels. ^{1 2 3 4 5}

How is the drug Temozolomide + Peginterferon different from other melanoma treatments?

This drug combines Temozolomide, an oral chemotherapy agent, with Peginterferon alfa-2b, a modified protein that boosts the immune system, potentially enhancing anti-tumor effects compared to using Temozolomide alone. ^{1 5 6 7 8}

What data supports the effectiveness of the drug Temozolomide + Peginterferon for treating melanoma?

Research shows that combining Temozolomide with interferon alpha-2b, including its pegylated form, may increase the effectiveness against melanoma, as both components are active in treating this condition. Studies have indicated improved response rates when these drugs are used together compared to using them alone. ^{1 2 3 4 5}

Who Is on the Research Team?

Alberto S. Pappo

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for children up to 21 years old with high-risk melanoma that can't be removed by surgery or has spread. They must have good liver, kidney, and bone marrow function and no history of severe depression, uncontrolled infections, certain heart diseases, poorly controlled diabetes or thyroid conditions. Prior treatment with dacarbazine or temozolomide disqualifies them.

Inclusion Criteria

My melanoma is at an advanced stage or has come back.

My liver and kidneys are working well.

My bone marrow is working well.

Exclusion Criteria

My diabetes is not well-managed with my current medication.

I have been hospitalized for depression or other mental health issues.

I am using steroids only for adrenal insufficiency, inhalers, or as premedication for transfusions or imaging.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy (Stratum A)

Subjects 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.

4 weeks

Maintenance Therapy (Stratum A)

Subjects receive peginterferon alfa-2b 1 mcg/kg/week subcutaneously for a total of 48 weeks.

48 weeks

Treatment Course (Stratum B)

Subjects 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 a 2-week break.

8 weeks per course, up to 7 courses

Follow-up

Participants are monitored for safety and effectiveness after treatment.

6 months to 12 months post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Peginterferon alfa-2b
• Temozolomide

Trial Overview The study tests the effectiveness of combining two drugs: Temozolomide and Peginterferon alfa-2b in treating pediatric patients with advanced melanoma. The aim is to see how well tumors respond to this combination therapy.

How Is the Trial Designed?

Group I: Temozolomide/peginterferon alfa-2b Experimental Treatment 2 Interventions

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.

Group II: Peginterferon alfa-2b/non-pegylated interferon alfa-2b Experimental Treatment 3 Interventions

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.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Schering-Plough

Industry Sponsor

Trials

163

Recruited

41,500+

Fred Hassan

Schering-Plough

Chief Executive Officer since 2003

PhD in Organic Chemistry from Harvard University

Dr. Robert J. Spiegel

Schering-Plough

Chief Medical Officer since 2006

MD from the University of Pennsylvania

Published Research Related to This Trial

In a phase I study involving 19 patients with advanced solid tumors, the maximum tolerated dose (MTD) of cyclical oral temozolomide (TMZ) was determined to be 100 mg/m² when combined with pegylated interferon alpha-2b (PEG-IFN-alpha-2b) at 1.5 mcg/kg/week.

The combination treatment did not alter the pharmacokinetics of PEG-IFN-alpha-2b, suggesting that it can be safely administered alongside TMZ without affecting its absorption or effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I, dose-escalation study of cyclical weekly oral temozolomide and weekly PEG-interferon alpha-2b in patients with refractory or advanced solid tumours. Coker, SA., Dandamudi, UB., Beelen, AP., et al.[2020]

In a phase II trial involving 46 patients with progressive low-grade glioma, Temozolomide (Temodar) demonstrated a 61% objective response rate, with 24% achieving complete response and 37% achieving partial response.

The treatment showed promising safety, with limited toxicity observed; however, one patient experienced severe complications, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of temozolomide in patients with progressive low-grade glioma. Quinn, JA., Reardon, DA., Friedman, AH., et al.[2022]

In a Phase I study involving 23 patients with metastatic melanoma, the combination of temozolomide (TMZ) and interferon alpha-2b (IFN-alpha2b) was found to be safe, with most adverse events being mild to moderate, and the primary dose-limiting toxicity being thrombocytopenia.

The treatment showed clinical activity, with 17% of patients achieving objective responses and a median survival of 9 months, suggesting that this regimen could be effective and warrants further research, especially regarding its impact on brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in combination with interferon alpha-2b in patients with metastatic melanoma: a phase I dose-escalation study. Agarwala, SS., Kirkwood, JM.[2018]

Citations

1. England pubmed.ncbi.nlm.nih.gov

A phase I, dose-escalation study of cyclical weekly oral temozolomide and weekly PEG-interferon alpha-2b in patients with refractory or advanced solid tumours. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II study of temozolomide plus pegylated interferon-alpha-2b for metastatic melanoma. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of temozolomide in patients with progressive low-grade glioma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG). [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Temozolomide in combination with interferon alpha-2b in patients with metastatic melanoma: a phase I dose-escalation study. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Phase II multicentre study of temozolomide in combination with interferon alpha-2b in metastatic malignant melanoma. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: a randomized, phase III, multicenter study from the Dermatologic Cooperative Oncology Group. [2018]