Pembrolizumab + Chemotherapy for Metastatic Melanoma

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wilson Miller

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: CNS lesions, Autoimmune disease, 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: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced melanoma, a type of skin cancer that cannot be surgically removed or has spread to other parts of the body. The researchers are testing a mix of chemotherapy drugs, carboplatin and paclitaxel, along with pembrolizumab, an immunotherapy drug designed to help the immune system fight cancer cells. Individuals with a confirmed diagnosis of advanced melanoma who have not received certain prior treatments might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in melanoma treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust these medications before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of pembrolizumab, carboplatin, and paclitaxel is generally safe for people with certain types of cancer. Studies have demonstrated promising results and a manageable safety profile for this combination. For instance, patients with head and neck cancer tolerated the treatment well.

Pembrolizumab, also known as KEYTRUDA®, has been studied for over ten years in advanced melanoma, a type of skin cancer. Many patients lived longer after receiving it. Although serious side effects can occur, they are uncommon.

Carboplatin and paclitaxel, chemotherapy drugs used for many years to treat various cancers, can cause side effects like nausea or hair loss. However, these effects are usually temporary and manageable.

Overall, the treatment shows promise, and many patients respond well to it. However, anyone considering joining a trial should consult their doctor about what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of pembrolizumab with chemotherapy for metastatic melanoma because it brings a fresh approach to fighting this aggressive cancer. Unlike traditional treatments that typically rely on chemotherapy alone, this combination includes pembrolizumab, an immunotherapy drug that ramps up the immune system to attack cancer cells more effectively. Pembrolizumab specifically targets the PD-1 pathway, which helps prevent cancer cells from hiding from the immune system. This dual approach of using both chemotherapy and immunotherapy has the potential to improve outcomes by not only attacking the tumor directly but also enhancing the body's natural defenses against cancer.

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

Research has shown that pembrolizumab, combined with the chemotherapy drugs carboplatin and paclitaxel, may be promising for treating advanced melanoma that has spread. This trial will study the combination of pembrolizumab, carboplatin, and paclitaxel. Studies have found that pembrolizumab can significantly improve survival rates in advanced melanoma, with more than one-third of patients living for over ten years. Compared to other treatments, pembrolizumab alone has effectively extended the lives of patients with advanced melanoma. By combining it with carboplatin and paclitaxel, researchers aim to enhance its effectiveness, particularly for those whose melanoma cannot be surgically removed. This combination is under study because pembrolizumab has already improved outcomes for melanoma patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Wilson Miller

Principal Investigator

Jewish General Hospital

Rahima Jamal, MD, PhD

Principal Investigator

CHUM, Hopital Notre-Dame

Are You a Good Fit for This Trial?

This trial is for adults over 18 with unresectable Stage III or metastatic melanoma who haven't had prior treatments for advanced melanoma (except BRAF/MEK inhibitors). Participants must have good organ function, not be pregnant, agree to contraception, and have no active infections like HIV or Hepatitis. Those with certain autoimmune diseases, symptomatic CNS lesions, severe neuropathy, or on immunosuppressants can't join.

Inclusion Criteria

My organs are functioning well.

I am using two birth control methods or am not having sex to avoid pregnancy during and up to 120 days after the study.

I can provide a tumor sample from a metastatic site for testing.

Exclusion Criteria

I have an autoimmune disease but it's controlled without strong medication, except for vitiligo, stable hypothyroidism, or mild asthma.

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

I am not on high-dose steroids or other drugs that weaken my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab, carboplatin, and paclitaxel every 3 weeks for up to 4 doses

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests pembrolizumab combined with carboplatin/paclitaxel in patients with advanced melanoma. It's an open-label Phase II trial where all participants receive the treatment to see how effective it is and what side effects occur.

How Is the Trial Designed?

Group I: Pembrolizumab, Carboplatin, Paclitaxel Experimental Treatment 3 Interventions

Carboplatin will be administered at AUC = 6, IV over 60 minutes every 3 weeks for up to 4 doses. Paclitaxel will be administered at 175mg/m2, IV over 3 hours every 3 weeks for up to 4 doses. Pembrolizumab will be administered at 200 mg, IV over 30 minutes every 3 weeks.

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?

Wilson Miller

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

Vemurafenib is an effective oral treatment for patients with inoperable and metastatic melanoma that have the BRAF V600E mutation, showing improved survival rates in clinical trials.

While vemurafenib is generally effective, it can cause significant side effects, including skin cancers, joint pain, fatigue, and heart rhythm changes, necessitating regular monitoring for these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vemurafenib for the treatment of melanoma. Jordan, EJ., Kelly, CM.[2018]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a study involving 173 patients with advanced melanoma who had not responded to previous treatments, pembrolizumab showed an overall response rate of 26% at both 2 mg/kg and 10 mg/kg doses, indicating its potential effectiveness in this challenging patient population.

The treatment was well tolerated with no drug-related deaths, and the safety profiles were similar across both doses, with fatigue, pruritus, and rash being the most common side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Robert, C., Ribas, A., Wolchok, JD., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

In a post hoc analysis of the KEYNOTE-006 study involving 555 patients with advanced melanoma, both ipilimumab and BRAF ± MEK inhibitors showed antitumor activity as subsequent therapies after pembrolizumab, with overall response rates (ORR) of 17.5% for ipilimumab and 30.5% for BRAF ± MEK inhibitors.

Patients who had not previously received BRAF ± MEK inhibitors showed a significantly higher ORR of 43.2% when treated with these agents after pembrolizumab, indicating that prior treatment status may influence the effectiveness of subsequent therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006. Long, GV., Arance, A., Mortier, L., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7331824/

Chemo-immunotherapy combination after PD-1 inhibitor ... In our study, ocular melanoma patients carry worse outcome even with CIT therapy, in line with their low response rates with the current standard of care. Their ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S221210992100073X

Cost-Effectiveness of Pembrolizumab Versus Carboplatin ... Pembrolizumab is projected as cost-effective compared with PC in patients with unresectable or metastatic melanoma after first-line treatment in China.

3. merck.com merck.com/news/ten-year-data-for-mercks-keytruda-pembrolizumab-demonstrates-sustained-overall-survival-benefit-versus-ipilimumab-in-advanced-melanoma/

Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01704287

NCT01704287 | Study of Pembrolizumab (MK-3475) ... This study was conducted to compare survival using pembrolizumab (SCH 900475, MK-3475) or standard chemotherapy in participants with advanced melanoma (MEL)

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10419154/

Efficacy of Pembrolizumab in Advanced Melanoma Regarding long-term outcomes, 5-year OS data for pembrolizumab in metastatic melanoma have been published, with reference to the KEYNOTE-001 studies [32] and ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02625

Pembrolizumab Plus Carboplatin and Paclitaxel as First- ... Pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity and a manageable safety profile in first-line R/M HNSCC.