Ipilimumab vs Interferon Alfa-2b for Skin Cancer

Recruiting at 1066 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

1673 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase III trial studies ipilimumab to see how well it works compared to high-dose interferon alfa-2b in treating patients with high-risk stage III-IV melanoma that has been removed by surgery. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of melanoma and other cancers. It is not yet known whether ipilimumab is more effective than interferon alfa-2b in treating patients with melanoma.

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.

What data supports the effectiveness of the drugs Ipilimumab and Interferon Alfa-2b for skin cancer?

Ipilimumab has been approved in the US for treating malignant melanoma, a type of skin cancer, by enhancing the body's immune response against tumor cells. Interferon Alfa-2b has shown antitumor activity in melanoma and is used as an additional therapy after surgery for high-risk melanoma. ^{1 2 3 4 5}

What safety data exists for Ipilimumab and Interferon Alfa-2b in humans?

Ipilimumab is linked to immune-related side effects like skin rashes, diarrhea, liver inflammation, and hormone gland issues, but these are often manageable with treatment. Interferon Alfa-2b can cause flu-like symptoms, fatigue, and mood changes, but these effects are generally known and monitored during treatment. ^{6 7 8 9 10}

How is the drug Ipilimumab different from other skin cancer treatments?

Ipilimumab is unique because it is a monoclonal antibody that blocks CTLA-4, a molecule that normally helps keep the immune system in check, thereby boosting the body's immune response against cancer cells. This mechanism is different from traditional treatments like chemotherapy, which directly target cancer cells. ^{1 2 3 4 11}

Research Team

Ahmad Tarhini

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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 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]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series. [2022]

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

Interferon Alfa-2b Adjuvant Therapy of High-Risk Resected Cutaneous Melanoma: The Eastern Cooperative Oncology Group Trial EST 1684. [2023]

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

Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Ipilimumab: first global approval. [2021]

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

Randomized trial of an allogeneic melanoma lysate vaccine with low-dose interferon Alfa-2b compared with high-dose interferon Alfa-2b for Resected stage III cutaneous melanoma. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Febrile neutropenia in a metastatic melanoma patient treated with ipilimumab - case report. [2017]

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

Ipilimumab in patients with cancer and the management of dermatologic adverse events. [2017]

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

Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Ipilimumab may increase the severity of cutenaous toxicity related to radiotherapy. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. [2022]

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

Acute rhabdomyolysis as a complication of interferon treatment for stage IIIc melanoma. [2018]