Temozolomide + Peginterferon for Melanoma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining two drugs, temozolomide and peginterferon alfa-2b, in treating melanoma, a type of skin cancer. The focus is on children and young adults with advanced or recurring melanoma that cannot be surgically removed. Treatment plans vary based on the stage and specific condition of the melanoma. This trial is suitable for those diagnosed with advanced melanoma who have not previously received certain chemotherapy drugs and have stable overall health. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining the drugs temozolomide and peginterferon alfa-2b has been studied for treating advanced solid tumors. In one study, patients with advanced melanoma received these drugs together, and they generally tolerated them well. However, some patients experienced side effects, such as flu-like symptoms, tiredness, and changes in blood cell counts.

The FDA has already approved peginterferon alfa-2b for treating certain types of melanoma when used alone. This approval indicates it is safe enough for use in people. However, like many treatments, it may cause side effects such as reactions at the injection site and tiredness.

Overall, both treatments have been used in people before, and evidence supports their safety, though some side effects are possible. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these melanoma treatments because they explore new ways to tackle the disease using a combination of drugs. The combination of Temozolomide and Peginterferon alfa-2b is unique as it pairs an oral chemotherapy agent (Temozolomide) with a subcutaneously injected immunotherapy (Peginterferon alfa-2b), potentially enhancing the body's immune response against cancer cells. Unlike the standard treatments, which often focus on surgical resection or intravenous chemotherapy, this approach offers a mix of oral and injectable therapies, which could improve patient experience and outcomes. Additionally, the use of pegylated interferon may offer a more sustained immune activation compared to non-pegylated forms, providing longer-lasting effects with less frequent dosing.

What evidence suggests that this trial's treatments could be effective for melanoma?

This trial will compare two treatment combinations for melanoma. One arm combines temozolomide and peginterferon alfa-2b. Research has shown that this combination may help treat melanoma, with previous studies indicating that about 18.1% of patients with advanced melanoma experienced tumor shrinkage, while 25% had stable cancer. Most patients tolerated the combination well, with manageable side effects. The other arm involves peginterferon alfa-2b combined with non-pegylated interferon alfa-2b. Peginterferon alfa-2b alone has also extended survival for some patients. Although not everyone benefits, these treatments have shown promise in managing advanced melanoma. ^{1 4 6 7 8}

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3481898/

Peginterferon-alfa-2b for the Adjuvant Treatment of ... Since the approval of PEG-IFN for melanoma, a meta-analysis of 14 interferon trials reported a modest, but statistically significant, survival advantage in ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1359610114001622

The use of interferon in melanoma patients: A systematic ... The use of IFN in patients with metastatic melanoma is controversial, with limited data and no convincing evidence of a survival benefit. However, IFN therapy ...

3. ar.iiarjournals.org ar.iiarjournals.org/content/32/9/3901

Update on PEG-Interferon α-2b as Adjuvant Therapy in ... In conclusion, this study showed that although adjuvant treatment with PEG-IFN for resected-stage III melanoma patients offers a significant sustained ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3043235/

Pharmacokinetic/pharmacodynamic analysis of adjuvant ... High-dose pegylated interferon α-2b (peginterferon α-2b) significantly decreased disease recurrence in patients with resected stage III melanoma in a clinical ...

5. ovid.com ovid.com/journals/exrder/fulltext/10.1586/edm.11.69~adjuvant-peginterferon-alfa-2b-therapy-in-stage-iii-melanoma

Adjuvant peginterferon alfa-2b therapy in stage III melanoma There was no statistically significant difference found between disease-free survival or OS when comparing IFN-α dose, treatment duration or any specific subset ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/103949s5252lbl.pdf

SYLATRON™ (peginterferon alfa-2b) for injection, for ... In a clinical study conducted in patients with melanoma, the incidence of binding antibodies to peg-interferon alfa-2b was approximately 35% (50/144 patients).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00539591

Phase II Study Incorporating Pegylated Interferon In the ... 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 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00049530

PEG-Interferon Alfa-2b in Treating Patients With Stage IV ... RATIONALE: Peginterferon (PEG-interferon) alfa-2b may stop the growth of cancer by stopping blood flow to the tumor. PURPOSE: Phase II trial to study the ...