Ipilimumab vs Interferon Alfa-2b for Skin Cancer

Not currently recruiting at 1097 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Systemic corticosteroids

Disqualifiers: Active infection, Autoimmune disorders, Depression, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 97

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug ipilimumab is more effective than interferon alfa-2b in treating high-risk skin cancer, specifically stage III-IV melanoma, after surgery. Ipilimumab, an immunotherapy, helps the immune system attack cancer cells, while interferon alfa-2b slows tumor growth. Individuals who have undergone surgery to remove melanoma and show no signs of the disease might be suitable candidates, particularly if their melanoma was at high risk of returning. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain treatments like systemic corticosteroids or have had recent infectious disease vaccinations. It's best to discuss your specific medications with the trial team.

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

Research has shown that ipilimumab is generally well-tolerated by patients with advanced melanoma. In studies involving 1,498 patients, ipilimumab demonstrated a predictable safety profile. Most side effects were mild, such as skin rashes or tiredness. However, some patients experienced more serious issues, like inflammation of the liver or intestines. The FDA has already approved ipilimumab for certain types of melanoma, supporting its safety in humans.

For recombinant interferon alfa-2b, studies have indicated it can cause more severe side effects. About 78% of patients experienced significant side effects, and many required dose adjustments. Common issues included flu-like symptoms, tiredness, and mood changes. Despite these side effects, it is also FDA-approved for melanoma, suggesting it is safe for use with careful monitoring.

In summary, both ipilimumab and recombinant interferon alfa-2b have established safety profiles, but recombinant interferon alfa-2b may lead to more severe side effects. Participants should discuss potential risks with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ipilimumab and recombinant interferon alfa-2b for skin cancer because they offer unique mechanisms of action compared to traditional treatments like chemotherapy and surgery. Ipilimumab is an immunotherapy that works by targeting CTLA-4, a protein that normally helps keep the immune system in check, thereby boosting the body's immune response against cancer cells. On the other hand, recombinant interferon alfa-2b is a type of cytokine therapy that enhances the immune system's ability to fight cancer by mimicking natural proteins in the body. These innovative approaches could potentially offer more targeted and effective treatment options with different side effect profiles than current standards.

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

Research shows that ipilimumab, one of the treatments in this trial, is a type of immunotherapy that can help the immune system fight melanoma by delaying the cancer's return by about 9 months on average. Approximately 10 to 20% of patients respond to this treatment, with 4-6% experiencing complete remission, meaning the cancer disappears entirely. In this trial, some participants will receive ipilimumab, while others will receive recombinant interferon alfa-2b. Studies suggest that interferon alfa-2b may help patients with high-risk melanoma live longer, increasing the average survival time to about 3.82 years compared to 2.78 years without the treatment. Both treatments offer potential benefits, but their effectiveness can vary from person to person. ^{6 7 8 9 10}

Who Is on the Research Team?

Ahmad Tarhini

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for patients with high-risk stage III-IV melanoma that's been surgically removed. Eligible participants must have certain blood test results, no history of specific medical conditions, and not be on treatments that could affect the trial. They can't have other cancers, active infections like HIV or hepatitis B/C, autoimmune disorders needing steroids, or vaccinations within 4 weeks prior to joining. Women who can become pregnant and men must use contraception.

Inclusion Criteria

I do not have any other types of cancer.

My breast cancer has spread to nearby lymph nodes but not to distant parts of my body.

I don't have health conditions that would make cancer treatment risky.

Exclusion Criteria

I have autoimmune thyroid disease or type 1 diabetes and am on replacement therapy.

I have stage IV melanoma with specific eligibility conditions.

You cannot have certain autoimmune diseases or conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive induction treatment with either high-dose ipilimumab, low-dose ipilimumab, or high-dose recombinant interferon alfa-2b

12 weeks

4 cycles every 21 days

Maintenance Treatment

Participants receive maintenance treatment with either high-dose ipilimumab, low-dose ipilimumab, or high-dose recombinant interferon alfa-2b

48 weeks

Every 90 days for ipilimumab or weekly for interferon

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Every 3 months for 2 years, every 6 months for 3 years, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Recombinant Interferon Alfa-2b

Trial Overview The study compares ipilimumab (an immunotherapy drug) with high-dose interferon alfa-2b (a treatment slowing cancer growth) in melanoma patients post-surgery. It aims to determine which is more effective at preventing cancer recurrence by either boosting the immune system or inhibiting tumor cell growth.

How Is the Trial Designed?

Group I: Arm F (ages 12-17, low-dose ipilimumab) Experimental Treatment 1 Intervention

Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 90 days for a maximum of 4 cycles in the absence of disease progression or unacceptable toxicity. (ages 12-17)

Group II: Arm E (ages 12-17, recombinant interferon alfa-2b) Experimental Treatment 1 Intervention

Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. (ages 12-17)

Group III: Arm D (age 12-17, high-dose ipilimumab) Experimental Treatment 1 Intervention

Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 90 days for a maximum of 4 cycles in the absence of disease progression or unacceptable toxicity.

Group IV: Arm C (age >= 18, low-dose ipilimumab) Experimental Treatment 2 Interventions

Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 cyclees in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 90 days for a maximum of 4 cycles in the absence of disease progression or unacceptable toxicity. (adult accrual has completed to Arms A, B, and C as of 8/15/2014)

Group V: Arm B (age >= 18, recombinant interferon alfa-2b) Experimental Treatment 2 Interventions

Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. (adult accrual has completed to Arms A, B, and C as of 8/15/2014)

Group VI: Arm A (age >= 18, high-dose ipilimumab) Experimental Treatment 2 Interventions

Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 90 days for a maximum of 4 cycles in the absence of disease progression or unacceptable toxicity. (closed accrual as of 4/4/14) (adult accrual has completed to Arms A, B, and C as of 8/15/2014)

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Ipilimumab (Yervoy®) is an approved monoclonal antibody for treating malignant melanoma by blocking the CTLA-4 protein, which enhances T-cell responses against tumor cells, showing its efficacy in cancer immunotherapy.

Currently, ipilimumab is also being tested in phase III trials for prostate cancer and phase II trials for non-small cell lung cancer, indicating its potential for broader applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: first global approval. Cameron, F., Whiteside, G., Perry, C.[2021]

Ipilimumab, a monoclonal antibody used to enhance anti-tumor T-cell responses, can cause significant side effects, including ipilimumab-induced hypophysitis (IH), which affects hormone levels and requires hormone replacement therapy in most cases.

In a review of 10 patients with IH, early detection and management guidelines were developed, highlighting the importance of monitoring hormone levels and recognizing imaging abnormalities, which often resolve without high-dose glucocorticoid therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series. Lam, T., Chan, MM., Sweeting, AN., et al.[2022]

Ipilimumab, a monoclonal antibody that enhances T-cell responses against tumors, has shown a survival benefit in patients with metastatic melanoma, both those who have been previously treated and those who are treatment-naïve.

While ipilimumab can cause mostly mild and reversible adverse events, particularly skin-related issues like rashes, following specific treatment guidelines can help manage these side effects effectively, ensuring better patient quality of life and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab in patients with cancer and the management of dermatologic adverse events. Lacouture, ME., Wolchok, JD., Yosipovitch, G., et al.[2017]

Ipilimumab, a monoclonal antibody that enhances the immune response against melanoma, can lead to immune-related adverse effects such as dermatitis, colitis, and hepatitis, which are typically managed with high-dose steroids.

In a reported case, a patient undergoing radiotherapy for metastatic melanoma developed an atypical generalized rash that worsened with concurrent ipilimumab treatment, highlighting the need for careful monitoring of skin reactions during combined therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab may increase the severity of cutenaous toxicity related to radiotherapy. Eryılmaz, MK., Mutlu, H., Salim, DK., et al.[2018]

Ipilimumab showed a best overall response rate (BORR) of 5.8% and a disease control rate (DCR) of 27% in patients with advanced melanoma, indicating some level of efficacy in this challenging population.

The treatment resulted in promising long-term survival rates, with 1- and 2-year survival rates of 47.2% and 32.8%, respectively, and a median overall survival of 10.2 months, while adverse events were primarily immune-related but manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. O'Day, SJ., Maio, M., Chiarion-Sileni, V., et al.[2022]

Citations

1. curemelanoma.org curemelanoma.org/patient-eng/melanoma-treatment/options/yervoy-ipilimumab

Ipilimumab, Yervoy - MRA The results showed that ipilimumab extended the amount of time before cancer returned by an average of 9 months.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6094709/

Ipilimumab for the treatment of melanoma - PMC Response rates ranged from 10 to 20% with approximately 4–6% of patients obtaining a durable complete remission (CR) [3–5]. These results were the foundation ...

3. news.bms.com news.bms.com/news/details/2021/Six-and-a-Half-Year-Outcomes-for-Opdivo-nivolumab-in-Combination-with-Yervoy-ipilimumab-Continue-to-Demonstrate-Durable-Long-Term-Survival-Benefits-in-Patients-with-Advanced-Melanoma/default.aspx

Six-and-a-Half-Year Outcomes for Opdivo (nivolumab) in ... With a minimum follow-up of 6.5 years, median overall survival (OS) was 72.1 months with Opdivo plus Yervoy (95% CI: 38.2-NR), the longest ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23942774/

Efficacy and safety of ipilimumab in metastatic melanoma ... Survival rates at 2 and 3 years were 25% (24 of 95) and 25% (13 of 53) with ipilimumab alone and 19% (54 of 284) and 15% (24 of 156) with ipilimumab plus gp100.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2772611825000060

Selecting first-line immunotherapy in advanced melanoma In BRAF WT disease, ipilimumab-nivolumab and nivolumab had similar outcomes (5-year PFS: 35 % vs 32 %, 5-year OS: 48 % vs 43 %, 10-year OS: 39 % vs 37 %).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4063401/

Ipilimumab and Its Toxicities: A Multidisciplinary Approach Ipilimumab is FDA-approved for use in the United States in patients with metastatic or unresectable stage III melanoma and in some other countries for patients ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/125377s110lbl.pdf

YERVOY (ipilimumab) - accessdata.fda.gov The safety of YERVOY was evaluated in MDX010-20, a randomized, double-blind clinical trial in which 643 previously treated patients with unresectable or ...

8. ascopubs.org ascopubs.org/doi/10.1200/jco.2011.29.15_suppl.8583

Ipilimumab safety profile: Summary of findings from ... Safety data were pooled from 1498 patients treated with ipilimumab at various doses, alone and in combination with various agents, and AEs in ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/yervoy-epar-product-information_en.pdf

Yervoy, INN-ipilimumab - EMA advanced melanoma. The safety data for patients with unresectable or metastatic melanoma, treated with ipilimumab. (3 mg/kg, with a minimum of 3 year follow ...

10. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)37101-7/fulltext

Efficacy and safety of ipilimumab in metastatic melanoma ... Survival rates at 2 and 3 years were 25% (24 of 95) and 25% (13 of 53) with ipilimumab alone and 19% (54 of 284) and 15% (24 of 156) with ipilimumab plus gp100.