High-Dose Interferon Alfa for Melanoma

Recruiting at 532 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ECOG-ACRIN Cancer Research Group

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

Compensation: Varies

Number of Visits: 23

Duration: 4 weeks

1150 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Interferon alfa may interfere with the growth of cancer cells. It is not yet known whether treatment with interferon alfa is more effective than observation alone for stage II or stage III melanoma that has been completely removed surgically. PURPOSE: This randomized phase III trial is studying high dose interferon alfa to see how well it works compared to observation only in treating patients with stage II or stage III melanoma that has been completely removed by surgery.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as systemic corticosteroids (like prednisone) and other immunosuppressive drugs, before participating. If you are on these medications, you will need to discuss with your doctor about stopping them.

What data supports the effectiveness of the drug Interferon alfa-2b for treating melanoma?

Research shows that high-dose Interferon alfa-2b can improve the time patients with high-risk melanoma remain free from cancer returning, although its impact on overall survival is less clear. Some studies suggest that the early, very-high-dose part of the treatment is crucial for its effectiveness. ^{1 2 3 4 5}

Is high-dose Interferon Alfa-2b safe for humans?

High-dose Interferon Alfa-2b can cause significant side effects, including flu-like symptoms, low blood cell counts, liver issues, thyroid problems, and mood changes. These side effects are often reversible with dose adjustments or stopping the treatment, but they can be severe enough to require some patients to stop treatment early. ^{3 6 7 8 9}

How is high-dose interferon alfa-2b different from other melanoma treatments?

High-dose interferon alfa-2b is unique because it is an adjuvant therapy (additional treatment given after the primary treatment) specifically approved for stage III melanoma, aiming to improve relapse-free survival. However, it is known for its significant side effects, which can limit its use, and its benefits in overall survival are still uncertain. ^{1 3 7 10 11}

Research Team

William E. Carson, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Alberto S. Pappo, MD

Principal Investigator

Texas Children's Cancer Center

Michael Smylie, MD, MB, ChB

Principal Investigator

Cross Cancer Institute at University of Alberta

Sanjiv S. Agarwala, MD

Principal Investigator

St. Luke's Cancer Network at St. Luke's Hospital

John M. Kirkwood, MD

Principal Investigator

UPMC Cancer Center at UPMC Presbyterian

Lawrence E. Flaherty, MD

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with stage II or III melanoma that's been surgically removed. They must have good organ function, no other cancers in the past 5 years, and not be pregnant or nursing. Participants need to use effective contraception and can't have autoimmune disorders, heart failure, a history of stroke or ischemic heart disease, cognitive impairments, or be on immunosuppressive treatments.

Inclusion Criteria

My skin cancer is at Stage II with a thickness of 1.5-4.0 mm.

My skin cancer is confirmed as melanoma.

My lymph nodes do not show signs of cancer, either by clinical exam or biopsy.

Exclusion Criteria

Clinical, radiological/laboratory, or pathological evidence of incompletely resected melanoma or any distant metastatic disease; Clinically palpable lymphadenopathy; Evidence of organic brain syndrome or significant impairment of basal cognitive function or any psychiatric disorder that would preclude study participation; Other significant medical or surgical condition, or any medication or treatment regimens, that would interfere with study participation; Pregnant or nursing; Other history of invasive melanoma; Autoimmune disorders or conditions of immunosuppression; History of active ischemic heart disease; Cerebrovascular disease; Congestive heart failure (New York Heart Association class III or IV heart disease); Prior or concurrent chemotherapy; Prior immunotherapy including tumor vaccines, interferon, interleukins, levamisole, or other biologic response modifiers for melanoma; Concurrent systemic corticosteroids including oral steroids (i.e., prednisone, dexamethasone), topical steroid creams or ointments, or any steroid-containing inhalers; Prior or concurrent radiotherapy; Other concurrent immunosuppressive medications

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high-dose interferon alfa-2b intravenously for 5 consecutive days weekly for 4 weeks

4 weeks

20 visits (in-person)

Observation

Participants undergo observation for 4 weeks

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

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

Treatment Details

Interventions

• Interferon alfa-2b

Trial Overview The study is testing high-dose interferon alfa against just observation to see which is better at preventing cancer growth after surgery. Patients are randomly assigned to either get the drug treatment or undergo regular monitoring without additional therapy.

Participant Groups

Group I: Observation Experimental Treatment 1 Intervention

Patients undergo observation for 4 weeks.

Group II: Interferon Alfa-2b Experimental Treatment 1 Intervention

Patients receive high-dose interferon alfa-2b IV over 20 minutes daily for 5 consecutive days. Treatment repeats weekly for 4 weeks in the absence of unacceptable toxicity.

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

Southwest Oncology Group

Collaborator

Trials

389

Recruited

260,000+

SWOG Cancer Research Network

Collaborator

Trials

403

Recruited

267,000+

NCIC Clinical Trials Group

Collaborator

Trials

190

Recruited

145,000+

Cancer and Leukemia Group B

Collaborator

Trials

81

Recruited

118,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Children's Oncology Group

Collaborator

Trials

467

Recruited

241,000+

Findings from Research

High-dose adjuvant interferon alpha-2b (IFN alpha 2b) improves quality-adjusted survival (QAS) for melanoma patients, with 77% of patients in one trial experiencing a benefit, although this was not statistically significant for all.

The effectiveness of IFN alpha 2b on QAS is influenced more by patients' perceptions of its toxicity rather than the fear of melanoma recurrence, indicating that cancer patients may have a higher tolerance for treatment side effects compared to the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality-of-life-adjusted survival analysis of high-dose adjuvant interferon alpha-2b for high-risk melanoma patients using intergroup clinical trial data. Kilbridge, KL., Cole, BF., Kirkwood, JM., et al.[2018]

High-dose interferon-alpha2b is an FDA-approved treatment for stage III melanoma, but its limited effectiveness and significant side effects make it a controversial choice among patients and doctors.

This paper aims to assess the benefits and risks of high-dose interferon-alpha2b, providing a framework to help oncologists support patients in making informed treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Helping melanoma patients decide whether to choose adjuvant high-dose interferon-alpha2b. Hurley, KE., Chapman, PB.[2018]

References

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

Two different durations of adjuvant therapy with intermediate-dose interferon alfa-2b in patients with high-risk melanoma (Nordic IFN trial): a randomised phase 3 trial. [2018]

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

Dose-dependent treatment benefit in high-risk melanoma patients receiving adjuvant high-dose interferon alfa-2b. [2018]

3. Greece pubmed.ncbi.nlm.nih.gov

Tolerability of adjuvant high-dose interferon alfa-2b: 1 month versus 1 year--a Hellenic Cooperative Oncology Group study. [2018]

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

Phase II pilot study of intravenous high-dose interferon with or without maintenance treatment in melanoma at high risk of recurrence. [2022]

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

Quality-of-life-adjusted survival analysis of high-dose adjuvant interferon alpha-2b for high-risk melanoma patients using intergroup clinical trial data. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Helping melanoma patients decide whether to choose adjuvant high-dose interferon-alpha2b. [2018]

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

Practical guidelines for the management of interferon-alpha-2b side effects in patients receiving adjuvant treatment for melanoma: expert opinion. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Toxicity of adjuvant high-dose interferon-alpha-2b in patients with cutaneous melanoma at high risk of recurrence. [2019]

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

Treatment of metastatic malignant melanoma with recombinant interferon alfa-2b. [2019]

11. England pubmed.ncbi.nlm.nih.gov

A randomised phase II trial of 1 month versus 1 year of adjuvant high-dose interferon α-2b in high-risk acral melanoma patients. [2022]