Ipilimumab +/− Interferon Alfa-2b for Advanced Skin Cancer

Recruiting at 319 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune disorders, Active infection, Pregnancy, 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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

88 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires a 4-week washout period (time without taking certain medications) between your last treatment and the start of the study therapy. If you are on systemic corticosteroids or other immunosuppressants, you must stop them at least 2 weeks before joining the trial, unless they are replacement doses for adrenal insufficiency.

What data supports the effectiveness of the drug Ipilimumab for advanced skin cancer?

Ipilimumab has been shown to improve overall survival in patients with advanced melanoma, a type of skin cancer, in clinical trials. It works by boosting the body's immune response against cancer cells, leading to durable tumor regression and long-term survival benefits. ^{1 2 3 4 5}

What safety information is available for Ipilimumab and Interferon Alfa-2b in humans?

Ipilimumab, also known as Yervoy, has been linked to immune-related side effects, including skin issues, digestive problems, liver and hormone-related events, and rare blood-related issues. Most side effects are mild to moderate, but some can be severe. Interferon Alfa-2b, known as Intron A or Roferon-A, is not specifically mentioned in the provided research, but it is generally known to have side effects like flu-like symptoms and fatigue. ^{2 6 7 8 9}

What makes the drug Ipilimumab unique for treating advanced skin cancer?

Ipilimumab is unique because it is an immunotherapy drug that works by blocking CTLA-4, a molecule that normally inhibits the immune system, thereby enhancing the body's ability to attack cancer cells. Unlike traditional chemotherapy, it can lead to a delayed but long-lasting response, improving overall survival in patients with advanced melanoma. ^{1 2 3 4 10}

What is the purpose of this trial?

This randomized phase II trial studies how well ipilimumab with or without high-dose recombinant interferon alpha-2b works in treating patients with stage III-IV melanoma that cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab, may block tumor growth by targeting certain cells. Recombinant interferon alfa-2b may interfere with the growth of tumor cells. It is not yet known whether ipilimumab is more effective with or without high-dose recombinant interferon alfa-2b in treating melanoma.

Research Team

Ahmad Tarhini

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults with stage III-IV melanoma that can't be surgically removed. Eligible participants must not have other current cancers (except certain cases), no brain metastasis, normal organ function tests, and no history of severe autoimmune diseases or conditions requiring systemic steroids. Women who can bear children and men must use effective contraception.

Inclusion Criteria

I haven't received any vaccines for infectious diseases in the last 4 weeks.

Your white blood cell count is at least 3000 per microliter.

My cancer's size and spread were checked within the last month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive ipilimumab and possibly recombinant interferon alfa-2b depending on the arm, with treatments administered over several weeks

12 weeks

Multiple visits for IV and SC administration

Maintenance

Continued administration of ipilimumab and possibly recombinant interferon alfa-2b, with treatments spaced out over a longer period

48 weeks

Regular visits every 12 weeks for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

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

Treatment Details

Interventions

• Ipilimumab
• Recombinant Interferon Alfa-2b

Trial Overview The study is testing the effectiveness of ipilimumab alone versus in combination with high-dose recombinant interferon alfa-2b in treating advanced melanoma. Ipilimumab is a monoclonal antibody that may block tumor growth by targeting specific cells, while interferon alfa-2b could interfere with tumor cell growth.

Participant Groups

Group I: Arm D (lower dose ipilimumab) Experimental Treatment 2 Interventions

INDUCTION PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses. MAINTENANCE PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24.

Group II: Arm C (lower dose ipilimumab + HDI) Experimental Treatment 3 Interventions

INDUCTION PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses and recombinant interferon alfa-2b IV over 20 minutes 5 days a week for 4 weeks and then SC 3 times weekly for 8 weeks. MAINTENANCE PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24 and recombinant interferon alfa-2b SC 3 times weekly for 48 weeks.

Group III: Arm B (higher dose ipilimumab) Experimental Treatment 2 Interventions

INDUCTION PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses. MAINTENANCE PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24.

Group IV: Arm A (higher dose ipilimumab, HDI) Experimental Treatment 3 Interventions

INDUCTION PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses and recombinant interferon alfa-2b IV over 20 minutes 5 days a week for 4 weeks and then SC 3 times weekly for 8 weeks. MAINTENANCE PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24 and recombinant interferon alfa-2b SC 3 times weekly for 48 weeks.

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 is a monoclonal antibody that enhances T cell activation by blocking the CTLA-4 receptor, leading to improved antitumor responses and has been shown to increase overall survival in patients with advanced melanoma, a condition with a poor prognosis.

While ipilimumab has demonstrated significant efficacy, it can cause serious immune-related adverse effects that require prompt management, highlighting the importance of monitoring patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. Graziani, G., Tentori, L., Navarra, P.[2020]

Ipilimumab (Yervoy) is the first new therapy approved for melanoma in over a decade, functioning as an antibody that blocks CTLA-4, which enhances the immune response against tumors, leading to durable tumor regression and improved overall survival in patients with advanced melanoma.

The clinical development of ipilimumab revealed its unique side effects profile and the long-lasting nature of its therapeutic responses, paving the way for future combination therapies with other checkpoint inhibitors currently being tested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory therapy for melanoma: ipilimumab and beyond. Callahan, MK., Postow, MA., Wolchok, JD.[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 (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]

In a phase 2 trial involving 142 patients with untreated advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 2-year overall survival rate of 63.8%, compared to 53.6% for those receiving ipilimumab alone, suggesting improved survival outcomes with the combination therapy.

However, the combination treatment was associated with a higher incidence of severe side effects, with 54% of patients experiencing grade 3-4 adverse events compared to 20% in the ipilimumab-only group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Hodi, FS., Chesney, J., Pavlick, AC., et al.[2022]

Ipilimumab, an immunotherapy for metastatic melanoma, can cause serious but rare haematological adverse events like anaemia and leukopenia in some patients, as seen in three cases presented in the study.

These haematological toxicities, while potentially severe, are manageable and can be effectively treated with corticosteroids, highlighting the importance of prompt recognition and intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious haematological toxicity during and after ipilimumab treatment: a case series. Simeone, E., Grimaldi, AM., Esposito, A., et al.[2021]

Ipilimumab has shown a positive impact on overall survival in patients with stage IV melanoma, with long-term follow-up indicating its effectiveness compared to conventional treatments.

While 84.8% of patients experience drug-related adverse events, most are mild to moderate; however, severe reactions can occur, necessitating careful monitoring and management, especially when combined with other therapies like vemurafenib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. Camacho, LH.[2022]

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. Netherlands pubmed.ncbi.nlm.nih.gov

Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. [2020]

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

Immunomodulatory therapy for melanoma: ipilimumab and beyond. [2021]

3. Australia pubmed.ncbi.nlm.nih.gov

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

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

Ipilimumab: first global approval. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. [2022]

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

Serious haematological toxicity during and after ipilimumab treatment: a case series. [2021]

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

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. 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]

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

Ipilimumab in melanoma. [2017]