DEC-C + Nivolumab for Melanoma

Overseen By Tessa McSpadden

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Colorado, Denver

Must not be taking: Immunosuppressants, Cytotoxic chemotherapy

Disqualifiers: Leptomeningeal disease, Active hepatitis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, Oral Decitabine/Cedazuridine (DEC-C) and Nivolumab (also known as Opdivo, an immunotherapy drug), to enhance the immune response against mucosal melanoma, a type of skin cancer. Researchers aim to determine if this combination can make immune cells more effective at attacking the cancer while reducing cancer-fighting inhibitors. The trial seeks participants with advanced mucosal melanoma, especially those who have already tried other immune-based treatments. Participants should have received these treatments within the last 30 days and have measurable disease through imaging or clinical exams. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel combination therapy.

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 be on drugs metabolized by CDA or on immunosuppressive therapy with more than 10mg/day of prednisone within 14 days of enrollment.

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

Research has shown that taking Oral Decitabine/Cedazuridine (DEC-C) with Nivolumab is usually safe for patients. This combination is being tested to determine its effectiveness for mucosal melanoma, a type of skin cancer. The safety of this treatment is a key focus, and results suggest it is generally safe, with most patients not experiencing serious side effects. However, mild side effects such as tiredness or nausea, common with immunotherapy, may occur. Patients should consult their doctor about the possible risks and benefits before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Oral Decitabine/Cedazuridine (DEC-C) combined with Nivolumab for mucosal melanoma because it offers a unique approach compared to existing treatments. While typical treatments like surgery, radiation, and immune checkpoint inhibitors are common, DEC-C introduces a novel oral formulation that combines decitabine with cedazuridine, potentially enhancing its effectiveness and making it easier to administer. Moreover, this combination targets the cancer with both a hypomethylating agent and an immune checkpoint inhibitor, which could provide a synergistic effect, offering hope for improved outcomes in a condition known for its challenges and limited options.

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

Research shows that using Oral Decitabine/Cedazuridine (DEC-C) with Nivolumab might effectively treat mucosal melanoma. In earlier studies, one patient achieved complete remission, three experienced partial remission, and five maintained stable disease. This suggests the combination could help manage the disease. Participants in this trial will receive this combination treatment, which strengthens the body's immune response to cancer cells, potentially enhancing Nivolumab's effectiveness. Using these treatments together might improve outcomes such as the duration patients live without cancer progression and overall survival. ^{1 3 4 6 7}

Who Is on the Research Team?

Martin McCarter

Principal Investigator

Colorado Research Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-100 with advanced mucosal melanoma, who may have had prior immune therapy. They must be able to undergo biopsies, have good organ function, and not be pregnant or breastfeeding. Participants need a negative pregnancy test and agree to use contraception if applicable. HIV-positive individuals can join if they meet certain conditions.

Inclusion Criteria

Women of childbearing potential must have a negative pregnancy test and agree to use effective contraceptive method

Patients must be willing to have archived tumor specimens utilized for correlative studies

My kidney function is normal.

Exclusion Criteria

I have cancer that has spread to the lining of my brain and spinal cord.

I do not have an active Hepatitis B or C infection.

I don't have any health issues that could affect the trial's results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ib Treatment

Participants receive DEC-C and Nivolumab to assess the RP2D using a TITE-BOIN design

Estimated 6-12 weeks

Phase II Treatment

Evaluate efficacy and safety of DEC-C and Nivolumab at the RP2D

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Oral Decitabine/Cedazuridine (DEC-C)

Trial Overview The study tests Oral Decitabine/Cedazuridine (DEC-C) combined with Nivolumab in patients with mucosal melanoma. It aims to see if DEC-C can boost the body's immune response against cancer by activating specific pathways and increasing tumor-fighting cells while on Nivolumab treatment.

How Is the Trial Designed?

Group I: Oral Decitabine/Cedazuridine (DEC-C) and Nivolumab in Mucosal Melanoma Experimental Treatment 1 Intervention

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

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Comprehensive Cancer Network

Collaborator

Trials

121

Recruited

7,400+

Taiho Oncology, Inc.

Industry Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Published Research Related to This Trial

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, 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]

Nivolumab significantly improved overall survival and progression-free survival in patients with unresectable or metastatic melanoma compared to dacarbazine, with hazard ratios of 0.42 and 0.43 respectively, based on a trial involving 418 patients.

The most common side effects of nivolumab included fatigue, diarrhea, and rash, but it was still considered to have a favorable benefit-risk profile compared to dacarbazine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. Beaver, JA., Theoret, MR., Mushti, S., et al.[2018]

A retrospective analysis of adverse events related to PD-1/PD-L1 inhibitors revealed a significant association between Pembrolizumab and hepatitis B reactivation (HBVr), with a reporting odds ratio of 2.32, indicating a higher risk compared to other treatments.

No cases of HBVr were reported with Ipilimumab or Avelumab, suggesting that not all immune checkpoint inhibitors carry the same risk, highlighting the need for further prospective studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. Burns, EA., Muhsen, IN., Anand, K., et al.[2023]

Nivolumab is shown to be the most cost-effective treatment option for advanced melanoma patients in England, with incremental cost-effectiveness ratios of £24,483 for BRAF mutation-negative and £17,362 for mutation-positive patients.

The analysis utilized a Markov state-transition model based on patient-level data from clinical trials, indicating that nivolumab provides long-term survival benefits while being economically favorable compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Meng, Y., Hertel, N., Ellis, J., et al.[2020]

In a real-world study of 709 patients with advanced melanoma treated with ipilimumab plus nivolumab, 50.7% experienced severe treatment-related adverse events, highlighting the need for careful monitoring during therapy.

Despite the high rate of adverse events, the combination therapy showed promising long-term survival outcomes, with a median overall survival of 28.7 months and a 4-year overall survival rate of 50% for patients similar to those in the CheckMate-067 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands. van Zeijl, MCT., van Breeschoten, J., de Wreede, LC., et al.[2023]

Nivolumab, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Nivolumab, a monoclonal antibody targeting the programmed death receptor-1, has shown promising efficacy in treating advanced malignant melanoma, with nearly 25% of patients achieving a partial tumor response in a phase II trial involving previously treated stage III/IV patients.

The treatment demonstrated a durable clinical benefit, with a median progression-free survival of 172 days and an acceptable safety profile, as less than 18% of patients experienced severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review of its use in patients with malignant melanoma. Deeks, ED.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05089370?cond=Melanoma&aggFilters=status:not%20rec%20enr%20act,phase:1%202%203&viewType=Table&rank=10

Oral Decitabine/Cedazuridine (DEC-C) in Combination ... Determine if the addition of DEC-C to Nivolumab increases progression free survival (PFS) and overall survival (OS) in unresectable, locally advanced, or ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11373357/

Advances in immunotherapy for mucosal melanoma One patient achieved complete remission, three attained partial remission, and five experienced stable disease.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-10828

Decitabine and Cedazuridine in Combination with ... Giving DEC-C and nivolumab may help control the disease in patients with stage III-IV mucosal melanoma. Eligibility Criteria ...

4. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05089370?keyword=%22Malignant%20Melanoma%22

Oral Decitabine/Cedazuridine (DEC-C) in Combination ... The results indicate that the objective response rate (ORR) to anti-PD1 in mucosal melanoma patients at our institution is 20%. The Investigator hypothesizes ...

5. jnccn.org jnccn.org/view/journals/jnccn/21/8/article-pxvi.xml

Highlights of the NCCN Oncology Research Program in This is a phase Ib/II investigator-initiated, open-label trial of the combination of oral decitabine/cedazuridine (DEC-C) and nivolumab ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT05089370

Oral Decitabine/Cedazuridine (DEC-C) in Combination ... Determine the safety of DEC-C in combination with Nivolumab unresectable, locally advanced, or metastatic mucosal melanoma patients. ... Download Trial Data.

7. jnccn.org jnccn.org/downloadpdf/view/journals/jnccn/21/8/article-pxvi.pdf

HIGHLIGHTS OF THE NCCN ONCOLOGY RESEARCH ... This is a phase Ib/II investigator-initiated, open-label trial of the combina- tion of oral decitabine/cedazuridine (DEC-C) and nivolumab treatments.