Ipilimumab + Chemotherapy for Melanoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jewish General Hospital

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune diseases, CNS lesions, 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: 5

Duration: 14 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it does exclude those using certain immunotherapies, immunosuppressive agents, or chronic systemic corticosteroids. It's best to discuss your current medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug combination of Ipilimumab, Carboplatin, and Paclitaxel for treating melanoma?

Research shows that combining ipilimumab with carboplatin and paclitaxel can provide long-term survival benefits for some patients with metastatic melanoma. Additionally, studies indicate that carboplatin and paclitaxel together have moderate activity against melanoma, making them a potential treatment option. ^{1 2 3 4 5}

Is the combination of Ipilimumab and chemotherapy safe for treating melanoma?

The combination of Ipilimumab with chemotherapy can lead to serious side effects, including immune-related adverse effects (irAE) and treatment-related adverse events (TRAEs). These can be severe and sometimes life-threatening, as seen in studies with other cancers, such as lung cancer, where higher rates of serious side effects were observed with this combination compared to chemotherapy alone. ^{6 7 8 9 10}

How is the drug combination of Ipilimumab, Carboplatin, and Paclitaxel unique for treating melanoma?

This drug combination is unique because it combines Ipilimumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with chemotherapy drugs Carboplatin and Paclitaxel, which directly kill cancer cells. This approach aims to enhance the immune response while simultaneously targeting the cancer with chemotherapy, offering a potentially more effective treatment for advanced melanoma. ^{1 11 12 13 14}

What is the purpose of this trial?

The safety of the combination of ipilimumab with carboplatin/paclitaxel treatment with two different dosing schedules will be investigated in patients with metastatic melanoma. This protocol will also investigate both the clinical benefit of this combination and the features of the host immune system that may predict response to ipilimumab with chemotherapy in patients with unresectable Stage III and Stage IV melanoma.

Research Team

Wilson Miller

Principal Investigator

Jewish General Hospital

Rahima Jamal, MD

Principal Investigator

Notre-Dame Hospital (CHUM)

Eligibility Criteria

This trial is for adults with advanced melanoma that can't be removed by surgery. Participants must have measurable disease, acceptable organ function, and no active infections like HIV or hepatitis. They should not have symptomatic brain lesions or autoimmune diseases, and must agree to use effective contraception.

Inclusion Criteria

Willing and able to give written informed consent

I have advanced melanoma that hasn't been treated with surgery, but I may have had adjuvant therapy or BRAF inhibitors.

You have a disease that can be measured or evaluated.

Exclusion Criteria

I have been cancer-free for less than a year, except for certain skin, bladder, or cervical cancers.

I have moderate to severe numbness, tingling, or pain in my hands or feet.

I am not on treatments like IL 2, interferon, other immune therapies, immunosuppressants, experimental drugs, or long-term steroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of Carboplatin, Paclitaxel, and Ipilimumab with two different dosing schedules

14 weeks

5 visits (in-person) for Carboplatin and Paclitaxel, 4 visits (in-person) for Ipilimumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Carboplatin
• Ipilimumab
• Paclitaxel

Trial Overview The trial tests the safety of combining ipilimumab (an immune therapy) with carboplatin/paclitaxel (chemotherapy) in two dosing schedules for metastatic melanoma. It aims to assess clinical benefits and identify immune system factors predicting response to treatment.

Participant Groups

Group I: B Experimental Treatment 3 Interventions

Carboplatin (week 1, week 4, week 7, week 10, and week 13) Paclitaxel (week 1, week 4, week 7, week 10, and week 13) Ipilimumab (week 5, week 8, week 11, and week 14)

Group II: A Experimental Treatment 3 Interventions

Arm A: Carboplatin (week 1, week 4, week 7, week 10, and week 13) Paclitaxel (week 1, week 4, week 7, week 10, and week 13) Ipilimumab (week 4, week 7, week 10, and week 13)

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Jewish General Hospital

Lead Sponsor

Trials

144

Recruited

283,000+

Findings from Research

In a study of 956 patients with advanced squamous non-small-cell lung cancer (NSCLC), the addition of ipilimumab to standard chemotherapy did not significantly improve overall survival compared to chemotherapy alone, with median survival times of 13.4 months versus 12.4 months, respectively.

The combination of ipilimumab and chemotherapy was associated with higher rates of severe treatment-related adverse events, including 51% experiencing grade 3 or 4 events, compared to 35% with chemotherapy plus placebo, indicating a need for careful consideration of safety in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III Trial of Ipilimumab Combined With Paclitaxel and Carboplatin in Advanced Squamous Non-Small-Cell Lung Cancer. Govindan, R., Szczesna, A., Ahn, MJ., et al.[2022]

Immune checkpoint inhibitors (ICIs) can lead to immune-related adverse events (irAEs) due to their mechanism of action, necessitating a multidisciplinary approach for effective patient management, as highlighted by 30 real-world pharmacovigilance studies.

These studies have provided valuable insights into the patterns, kinetics, and fatality rates of various irAEs, emphasizing the need for oncologists to understand both the strengths and limitations of this data for better patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance. Raschi, E., Gatti, M., Gelsomino, F., et al.[2021]

Immunotherapy use for treating cancers like metastatic melanoma and lung cancer is increasing and is similarly effective in both regional and tertiary oncology services, based on a 5-year review of patient records.

Patients in regional services experience earlier identification and treatment of immune-related adverse effects (irAE), leading to shorter immunosuppression periods and less need for hospitalization, indicating a safe and effective management approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of immunotherapy use and management of toxicities in regional and tertiary settings. Hamilton, B., Xu, K., Honeyball, F., et al.[2023]

In a meta-analysis of 11,465 patients from 18 clinical trials, PD-1/PD-L1 inhibitors were found to significantly increase the risk of developing dermatologic adverse effects like rash and pruritus compared to chemotherapy, with relative risks of 1.84 and 3.74, respectively.

PD-1/PD-L1 inhibitors showed a lower risk of mucosal inflammation and alopecia compared to chemotherapy, indicating a distinct safety profile that differs from traditional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. Yang, W., Li, S., Yang, Q.[2021]

In a study of 945 patients with untreated metastatic melanoma, the combination of nivolumab and ipilimumab significantly improved progression-free survival to a median of 11.5 months compared to just 2.9 months with ipilimumab alone.

For patients with PD-L1-negative tumors, the combination therapy was particularly effective, showing a progression-free survival of 11.2 months compared to 5.3 months with nivolumab alone, highlighting the potential of dual checkpoint inhibition in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. Larkin, J., Chiarion-Sileni, V., Gonzalez, R., et al.[2023]

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]

References

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

Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma. [2019]

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

Phase II study of paclitaxel and carboplatin for malignant melanoma. [2020]

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

A phase II trial of nab-paclitaxel (ABI-007) and carboplatin in patients with unresectable stage IV melanoma : a North Central Cancer Treatment Group Study, N057E(1). [2021]

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

Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma. [2021]

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

Phase III trial of carboplatin and paclitaxel with or without sorafenib in metastatic melanoma. [2021]

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

A phase II study of carboplatin, cisplatin, interferon-alpha, and tamoxifen for patients with metastatic melanoma. [2019]

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

Phase III Trial of Ipilimumab Combined With Paclitaxel and Carboplatin in Advanced Squamous Non-Small-Cell Lung Cancer. [2022]

8. France pubmed.ncbi.nlm.nih.gov

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance. [2021]

9. Australia pubmed.ncbi.nlm.nih.gov

Patterns of immunotherapy use and management of toxicities in regional and tertiary settings. [2023]

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

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. [2021]

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

Randomized phase I pharmacokinetic study of ipilimumab with or without one of two different chemotherapy regimens in patients with untreated advanced melanoma. [2021]

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

Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): a randomised, double-blind, placebo-controlled, phase 2 trial. [2020]

14. 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]