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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for individuals with advanced melanoma, a type of skin cancer that has spread and cannot be surgically removed. The researchers aim to determine if using ipilimumab (a drug that helps the immune system fight cancer) with two chemotherapy drugs, carboplatin and paclitaxel, is safe and beneficial. The trial employs two different schedules to identify the most effective approach and examines immune system markers that might indicate who will benefit most. Individuals who have not received prior treatment for their advanced melanoma and have measurable disease may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that combining ipilimumab with carboplatin and paclitaxel is generally safe. In one study, many patients completed the entire treatment, indicating that most side effects were not too severe. However, serious side effects can occur with ipilimumab alone. Specifically, about 26% of people experienced severe or life-threatening side effects when taking only ipilimumab. Adding carboplatin and paclitaxel to ipilimumab did not significantly increase these serious side effects.

Overall, while risks exist, most patients tolerate the treatment well. Prospective trial participants should consult their doctor to understand what this might mean for them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Ipilimumab with chemotherapy for melanoma because this approach could enhance the body's immune response against cancer cells. Unlike traditional treatments like targeted therapy or standalone chemotherapy, Ipilimumab is an immunotherapy that works by activating the immune system's T-cells to better recognize and attack melanoma cells. This combination therapy has the potential to improve outcomes by both directly killing cancer cells with chemotherapy while also boosting the immune system's ability to fight the cancer. The unique scheduling of Ipilimumab alongside Carboplatin and Paclitaxel aims to maximize this dual attack, offering hope for a more effective treatment strategy against melanoma.

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

Research has shown that ipilimumab, when combined with the chemotherapy drugs carboplatin and paclitaxel, may help treat advanced melanoma. In this trial, participants will receive different schedules of these treatments. Ipilimumab boosts the immune system and has extended the lives of some melanoma patients. Studies suggest that combining it with these chemotherapy drugs might improve outcomes when other treatments have failed. This combination enhances the immune system's ability to locate and destroy cancer cells. While these findings are promising, results can vary for each individual. ^{3 4 5 6 7}

Who Is on the Research Team?

Wilson Miller

Principal Investigator

Jewish General Hospital

Rahima Jamal, MD

Principal Investigator

Notre-Dame Hospital (CHUM)

Are You a Good Fit for This Trial?

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

You have a disease that can be measured or evaluated.

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9096114/

Outcomes From Cytotoxic Chemotherapy Following ... Our results reveal that receipt of immunotherapy prior to chemotherapy for metastatic melanoma does not appear to improve the benefit of chemotherapy.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29157311/

Peripheral and local predictive immune signatures ... Background: Checkpoint blockade with ipilimumab provides long-term survival to a significant proportion of patients with metastatic melanoma.

3. ascopubs.org ascopubs.org/doi/10.1200/jco.2014.32.15_suppl.9066

A randomized phase II study of ipilimumab (IPI) with ... One-year overall survival (OS) and biomarker correlates from a phase II study of ipilimumab (IPI) with carboplatin and paclitaxel (CP) in ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT244963

Chemo-immunotherapy combination after PD-1 inhibitor ... Chemo-immunotherapy combination after PD-1 inhibitor failure improves clinical outcomes in metastatic melanoma patients. Chemo-immunotherapy combination after ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419370267

Ipilimumab in combination with paclitaxel and carboplatin ... Ipilimumab, an anti-CTLA4 monoclonal antibody, demonstrated survival benefit in melanoma with immune-related (ir) adverse events (irAEs) managed by the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6329845/

Incidence of Ipilimumab-Related Serious Adverse Events in ... The overall incidence of SAEs during ipilimumab mono-therapy was 26.1% (95% CI, 21.1%-31.8%). SAEs were more frequent in the 10 mg/kg groups than in the 3 mg/ ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01676649

Ipilimumab With Carboplatin and Paclitaxel in Patients ... The safety of the combination of ipilimumab with carboplatin/paclitaxel treatment with two different dosing schedules will be investigated in patients with ...