NovoTTF-200A + Pembrolizumab for Melanoma

Recruiting at 1 trial location

Overseen By Eric T Wong, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eric Wong, MD

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 69

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study involves studying a device as a possible treatment for metastatic melanoma in the brain. The purpose of this study is to obtain information on the safety and effectiveness of the study device, NovoTTF-200A, in melanoma participants with brain metastases when it is combined with Pembrolizumab. The name of the study device involved in this study is: -- NovoTTF-200A The name of the drug used in this study is: -- Pembrolizumab

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have had chemotherapy or radiotherapy within 4 weeks before the trial or if you are on systemic steroid therapy at a dose equivalent to 4 mg daily of dexamethasone or more within 7 days prior to the trial.

What data supports the effectiveness of the drug pembrolizumab for treating melanoma?

Pembrolizumab has been shown to improve survival and response rates in patients with advanced melanoma, as demonstrated in several clinical trials. It is approved for use in patients who have not responded to other treatments, showing significant benefits in progression-free survival and overall response rates. ^{1 2 3 4 5}

Is the combination of NovoTTF-200A and Pembrolizumab safe for treating melanoma?

Pembrolizumab, also known as KEYTRUDA, has been shown to be generally safe in humans, with common side effects including fatigue, rash, itching, and diarrhea. Less common side effects can include thyroid issues, lung inflammation, and liver inflammation. Safety data for NovoTTF-200A specifically in combination with Pembrolizumab is not detailed in the provided research. ^{4 6 7 8 9}

What makes the NovoTTF-200A + Pembrolizumab treatment unique for melanoma?

The combination of NovoTTF-200A, a device that uses electric fields to disrupt cancer cell division, with Pembrolizumab, an immune-boosting drug, offers a novel approach by targeting melanoma through both physical and immune mechanisms, which is different from standard treatments that typically focus on one method. ^{1 3 4 5 9}

Research Team

Eric Wong, MD

Principal Investigator

Lifespan Cancer Institute

Eligibility Criteria

Adults with melanoma that has spread to the brain can join this trial. They need measurable disease, a life expectancy over 6 months, and normal organ/marrow function. Participants must be willing to use birth control and have support for device treatment. Excluded are those recently on certain therapies, with hypersensitivities or other cancers, serious health issues like heart conditions or infections, pregnant/breastfeeding women, or uncontrolled illnesses.

Inclusion Criteria

My organs and bone marrow are functioning normally.

You are expected to live for more than 6 months.

I have taken a pregnancy test in the last 14 days and it was negative.

Exclusion Criteria

My cancer has spread to the lining of my brain and spinal cord.

Participants who are receiving any other investigational agents

I have been treated for an autoimmune disease in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive NovoTTF-200A continuously and Pembrolizumab every 3 weeks in a 3+3 design cohort

21 days per cycle

Continuous device use, Pembrolizumab every 3 weeks

Phase II Treatment

Participants continue to receive NovoTTF-200A continuously and Pembrolizumab every 3 weeks

21 days per cycle

Continuous device use, Pembrolizumab every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Visits at 63, 129, 189 days, and 30 days after last treatment

Treatment Details

Interventions

• NovoTTF-200A
• Pembrolizumab

Trial Overview The study is testing NovoTTF-200A (a device) combined with Pembrolizumab (a drug) for safety and effectiveness in treating brain metastases from melanoma. The goal is to see how well these treatments work together against this advanced stage of skin cancer.

Participant Groups

Group I: PHASE 2: NovoTTF-200A + PEMBROLIZUMAB Experimental Treatment 2 Interventions

* NovoTTF-200A will be applied continuously, with 21 consecutive days defined as a treatment cycle. * Pembrolizumab will be administered once every 3 weeks, with 21 consecutive days also defined as a treatment cycle

Group II: PHASE 1: NovoTTF-200A + PEMBROLIZUMAB Experimental Treatment 2 Interventions

The Phase I portion of the study will have a 3 + 3 design and consist of one cohort treated * NovoTTF-200A will be applied continuously, with 21 consecutive days defined as a treatment cycle. * Pembrolizumab will be administered once every 3 weeks, with 21 consecutive days also defined as a treatment cycle

Who Is Running the Clinical Trial?

Eric Wong, MD

Lead Sponsor

Trials

1

Recruited

30+

Brown University

Lead Sponsor

Trials

480

Recruited

724,000+

NovoCure Ltd.

Industry Sponsor

Trials

64

Recruited

6,100+

Ashley Cordova

NovoCure Ltd.

Chief Executive Officer

Bachelor of Science in Material Engineering from Ben-Gurion University of the Negev, Israel

Uri Weinberg

NovoCure Ltd.

Chief Medical Officer since 2020

MD from an unspecified institution

Findings from Research

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 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]

Pembrolizumab (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[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]

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]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

In a study of 103 Chinese patients with advanced melanoma, pembrolizumab demonstrated a 16.7% objective response rate, indicating its effectiveness as a second-line treatment, particularly in aggressive melanoma subtypes.

The treatment was well tolerated, with 84.5% of patients experiencing treatment-related adverse events, but only a small percentage (8.7%) had severe side effects, and no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). Si, L., Zhang, X., Shu, Y., et al.[2020]

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, 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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

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

Pembrolizumab: A Review in Advanced Melanoma. [2022]

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

Pembrolizumab: first global approval. [2021]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

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

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). [2020]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. [2020]