Malignant MelanomaPhase 1/2NCT05089370
Oral Decitabine/Cedazuridine (DEC-C) in Combination With Nivolumab for Patients With Mucosal Melanoma
A Phase 1/2 study testing Oral Decitabine/Cedazuridine (DEC-C) in Combination with Nivolumab in people with Malignant Melanoma, run by University of Colorado, Denver at 1 site in United States.
Trial summary
Activation of the RIG-I innate immune pathway and increased expression of tumor antigens and pro-immune genes by DEC-C during Nivolumab treatment may enhance the frequency and activity of anti-tumor immune cells (CD4+ and CD8+ T-cells, NK cells) and reduce the frequency and activity of immunosuppressive cells. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- Oral Decitabine/Cedazuridine (DEC-C) in Combination with Nivolumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jun 2022to Oct 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision to sign and date the consent form.
- Stated willingness to comply with all study procedures and be available for the duration of the study.
- Be a male or female aged 18-100.
- Histologically confirmed diagnosis of advanced mucosal melanoma (unresectable Stage III or Stage IV Melanoma). Anatomical locations for primary site of mucosal melanoma include oral cavity (excluding lip), nasopharynx, vagina/vulva, and rectum.
- Prior immune checkpoint blockade therapy, including anti-PD1 and anti-CTLA4 for unresectable locally advanced or metastatic disease, is allowed. The combination of anti-PD1 and anti-CTLA4 is also allowed as a prior line of therapy. Study therapy must be initiated within 30 days of previous immune checkpoint blockade therapy (excluding adjuvant anti-PD1 and anti-CTLA4).
- Patients must have systemic cross-sectional imaging (PET/CT or CT of chest, abdomen, and pelvis) with radiographically measurable, by immune-RECIST (RECIST) criteria, or clinically measurable disease.
Show all 15Show fewer
- Previously treated brain metastatic disease is allowed. Stability of brain metastases must be confirmed by MRI > 4 weeks from most recent treatment and within 4 weeks of initiating study therapy.
- Patients must have an ECOG performance status of 0 or 1 (Table 5).
- Patients must have adequate bone marrow function as evidenced by all of the following: ANC ≥ 2,500 microliter (mcL); platelets ≥ 100,000/mcL; Hemoglobin ≥ 10 g/dL.
- Patients must have adequate hepatic function as evidenced by the following: total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) (except Gilbert's Syndrome, who must have a total bilirubin < 3.0 mg/dL), and SGOT (AST) and SGPT (ALT) and alkaline phosphatase ≤ 2.5 x ULN.
- Patients must have adequate renal function as evidenced by ONE of the following: serum creatinine ≤ 2.0 x ULN OR measured or calculated creatinine clearance ≥ 40 mL/min.
- Patients known to be HIV positive are eligible if they meet the following criteria within 30 days prior to registration: stable and adequate CD4 counts (≥ 350 mm3), and serum HIV viral load of < 25,000 IU/ml. Patients may be on or off anti-viral therapy so long as they meet the CD4 count criteria.
- Women of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. Women/men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. A woman is considered to be of "reproductive potential" as defined in section 5.3.2.
- Patients must be willing to have archived tumor specimens utilized for correlative studies if available.
- Patients must consent to have biopsies performed prior to treatment and around cycle 2 during study. However, in the event that tumor is inaccessible, the biopsy is not in the subject's best interest, or the patient refuses biopsy during course of the study, patients will be allowed to remain on study.
Who cannot join
- No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, lobular carcinoma of the breast in situ, atypical melanocytic hyperplasia or melanoma in situ, treated and stable thyroid cancer, adequately treated Stage I cancer (including multiple primary melanomas) from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
- Patients must not currently be on other drugs metabolized by CDA.
- Prior cytotoxic chemotherapy treatment received within 30 days of study enrollment.
- Patients with leptomeningeal disease.
- Current immunosuppressive therapy including >10mg/day of prednisone within 14 days of enrollment is not permitted. Inhaled or topical steroids, and adrenal replacement steroid doses ≤10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- Patients must not have known active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection prior to registration.
Show all 12Show fewer
- Patients must not have active autoimmune disease that has required systemic treatment in past 2 years from date of enrollment (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Patients must not have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Patients must not have received live vaccines within 42 days prior to enrollment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza and COVID-19 vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Patients must not have a history or current evidence of any condition, therapy or laboratory abnormality that might confound the trial results, interfere with the patient's participation for the full duration of the trial, or indicate that participation in the trial is not in the patient's best interests, in the opinion of the treating investigator.
- Patients must not be pregnant or lactating.
- Treatment with any investigational agent within 30 days of first administration of study treatment is not permitted.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Hospital
Aurora, Colorado, 80045
About this study
Official title: Oral Decitabine/Cedazuridine (DEC-C) in Combination With Nivolumab as a Strategy to Enhance the Efficacy of Immune Checkpoint Blockade in Unresectable or Metastatic Mucosal Melanoma
Activation of the RIG-I innate immune pathway and increased expression of tumor antigens and pro-immune genes by DEC-C during Nivolumab treatment may enhance the frequency and activity of anti-tumor immune cells (CD4+ and CD8+ T-cells, NK cells) and reduce the frequency and activity of immunosuppressive cells. This may increase the overall effectiveness and success of Nivolumab treatment. This pilot clinical trial will demonstrate whether combinatorial immunotherapeutic approaches that target epigenetic immune repression and RIG-I activity can favorably alter the tumor immune cell microenvironment and benefit patients with mucosal melanoma.
Read the detailed description
This is a Phase Ib/II investigator-initiated open label trial of the combination of DEC-C and Nivolumab treatment.
This is a single-center study to be conducted at the University of Colorado Cancer Center (UCHealth central campus). A complete and current listing of investigators, research personnel, and research facilities participating in this study will be maintained throughout the duration of this study on applicable study required forms such as an FDA Form 1572, the COMIRB Research Personnel Form, and/or a UCCC Protocol Contact List, incorporated herein by reference.
Phase Ib: A time-to-event Bayesian optimal interval (TITE-BOIN) design will be used to assess the RP2D during phase 1b. The BOIN design is a model assistant approach used in phase I clinical trials for finding the maximum tolerated dose (MTD). The Investigator anticipates a maximum of 9 patients treated at the RP2D in Phase 1b dose de-escalation and considers as subjects in stage 1 of phase 2.
Phase II: The objective of Phase II is to preliminarily evaluate the efficacy and further evaluate safety of the combination at the RP2D. The phase II cohort will enroll patients using the established RP2D of DEC-C from the phase Ib portion in combination with standard doses of Nivolumab. Patients treated at the RP2D in Phase 1b will be included in analysis for the Phase II component of this study. All patients enrolled at the RP2D level and receiving any DEC-C treatment will be included in the efficacy and safety/tolerability endpoint analysis. The results indicate that the objective response rate (ORR) to anti-PD1 in mucosal melanoma patients at our institution is 20%. The Investigator hypothesizes ORR for the combination will be 43%, a 23% absolute improvement over the anti-PD1 treatment. Simon's 2-stage design will be used to evaluate the ORRs. The null hypothesis that the ORR is 20% will be rejected if there are 3 or more responses among the 11 patients (including phase Ib RP2D patients). The design yields a type I error rate of 001 and power of 80% when the true response rate is 43%. The total sample size required for the Phase II will depend on the number of patients treated at the RP2D during Phase 1b, and it is estimated the total sample size will be in the range of 19-21 subjects.
- Conditions
- Malignant Melanoma
- Being tested
- Oral Decitabine/Cedazuridine (DEC-C) in Combination with Nivolumab
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Decitabine/Cedazuridine (DEC-C) in Combination with NivolumabCombination product
Activation of the RIG-I innate immune pathway and increased expression of tumor antigens and pro-immune genes during Nivolumab treatment may enhance the frequency and activity of anti-tumor immune cells (CD4+ and CD8+ T-cells, NK cells) and reduce the frequency and activity of immunosuppressive cells (MDSCs, Tregs) (1-4), increasing the overall effectiveness and success of Nivolumab treatment. This pilot clinical trial will demonstrate whether combinatorial immunotherapeutic approaches that target epigenetic immune repression and RIG-I activity can favorably alter the tumor immune cell microenvironment and benefit mucosal melanoma patients.
| Study group | Role | What they receive |
|---|---|---|
| Oral Decitabine/Cedazuridine (DEC-C) and Nivolumab in Mucosal Melanoma | Experimental | Not described Receives: Combination Product: Oral Decitabine/Cedazuridine (DEC-C) in Combination with Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the safety of DEC-C in combination with Nivolumab unresectable, locally advanced, or metastatic mucosal melanoma patients.
Determine the safety and tolerability of DEC-C in combination with Nivolumab by evaluating adverse events (AEs) using CTCAEv5.0 criteria and establishing the recommended phase 2 dose (RP2D) of DEC-C.
Measured: 24 months
Secondary outcomes (2)
Determine the response rate to DEC-C in combination with Nivolumab in unresectable, locally advanced, or metastatic mucosal melanoma patients
Evaluate the rate of subjects that achieve an objective response (ORR) to DEC-C in combination with Nivolumab by radiographic assessment using iRECIST criteria.
Measured: 24 months
Determine if the addition of DEC-C to Nivolumab increases progression free survival (PFS) and overall survival (OS) in unresectable, locally advanced, or metastatic mucosal melanoma patients.
Evaluate and estimate progression free survival (PFS) and overall survival (OS) in unresectable locally advanced and metastatic mucosal melanoma patients at 24 months post-study.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2021
- Study start20 Jun 2022
- Primary completion10 Aug 2026
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is an open-label, single-arm trial.
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Comprehensive Cancer Network, Taiho Oncology, Inc.
- Responsible party
- Sponsor
- Investigators
- Martin McCarter, Principal investigator, Colorado Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05089370
- Sponsor's protocol ID
- 21-3518.cc
- Other IDs
- NCI-2021-10828, 2021-IST-DECC-000076
- Status last verified
- Dec 2025
- First submitted
- 11 Oct 2021
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data may be shared with the NCCN per research agreement.
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Decitabine/Cedazuridine (DEC-C) in Combination With Nivolumab as a Strategy to Enhance the Efficacy of Immune Checkpoint Blockade in Unresectable or Metastatic Mucosal Melanoma
- ClinicalTrials.gov ID
- NCT05089370
- Acronym / sponsor ID
- 21-3518.cc
- Conditions
- Malignant Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Comprehensive Cancer Network, Taiho Oncology, Inc.
- Study start
- 20 Jun 2022 (actual)
- Primary completion
- 10 Aug 2026 (actual)
- Study completion
- Oct 2026 (estimated)
- First posted
- 22 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Activation of the RIG-I innate immune pathway and increased expression of tumor antigens and pro-immune genes by DEC-C during Nivolumab treatment may enhance the frequency and activity of anti-tumor immune cells (CD4+ and CD8+ T-cells, NK cells) and reduce the frequency and activity of immunosuppressive cells. This may increase the overall effectiveness and success of Nivolumab treatment. This pilot clinical trial will demonstrate whether combinatorial immunotherapeutic approaches that target epigenetic immune repression and RIG-I activity can favorably alter the tumor immune cell microenvironment and benefit patients with mucosal melanoma.
Detailed description
This is a Phase Ib/II investigator-initiated open label trial of the combination of DEC-C and Nivolumab treatment.
This is a single-center study to be conducted at the University of Colorado Cancer Center (UCHealth central campus). A complete and current listing of investigators, research personnel, and research facilities participating in this study will be maintained throughout the duration of this study on applicable study required forms such as an FDA Form 1572, the COMIRB Research Personnel Form, and/or a UCCC Protocol Contact List, incorporated herein by reference.
Phase Ib: A time-to-event Bayesian optimal interval (TITE-BOIN) design will be used to assess the RP2D during phase 1b. The BOIN design is a model assistant approach used in phase I clinical trials for finding the maximum tolerated dose (MTD). The Investigator anticipates a maximum of 9 patients treated at the RP2D in Phase 1b dose de-escalation and considers as subjects in stage 1 of phase 2.
Phase II: The objective of Phase II is to preliminarily evaluate the efficacy and further evaluate safety of the combination at the RP2D. The phase II cohort will enroll patients using the established RP2D of DEC-C from the phase Ib portion in combination with standard doses of Nivolumab. Patients treated at the RP2D in Phase 1b will be included in analysis for the Phase II component of this study. All patients enrolled at the RP2D level and receiving any DEC-C treatment will be included in the efficacy and safety/tolerability endpoint analysis. The results indicate that the objective response rate (ORR) to anti-PD1 in mucosal melanoma patients at our institution is 20%. The Investigator hypothesizes ORR for the combination will be 43%, a 23% absolute improvement over the anti-PD1 treatment. Simon's 2-stage design will be used to evaluate the ORRs. The null hypothesis that the ORR is 20% will be rejected if there are 3 or more responses among the 11 patients (including phase Ib RP2D patients). The design yields a type I error rate of 001 and power of 80% when the true response rate is 43%. The total sample size required for the Phase II will depend on the number of patients treated at the RP2D during Phase 1b, and it is estimated the total sample size will be in the range of 19-21 subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is an open-label, single-arm trial.
| Arm | Type | Receives |
|---|---|---|
| Oral Decitabine/Cedazuridine (DEC-C) and Nivolumab in Mucosal Melanoma | Experimental | Combination Product: Oral Decitabine/Cedazuridine (DEC-C) in Combination with Nivolumab |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Provision to sign and date the consent form.
- Stated willingness to comply with all study procedures and be available for the duration of the study.
- Be a male or female aged 18-100.
- Histologically confirmed diagnosis of advanced mucosal melanoma (unresectable Stage III or Stage IV Melanoma). Anatomical locations for primary site of mucosal melanoma include oral cavity (excluding lip), nasopharynx, vagina/vulva, and rectum.
- Prior immune checkpoint blockade therapy, including anti-PD1 and anti-CTLA4 for unresectable locally advanced or metastatic disease, is allowed. The combination of anti-PD1 and anti-CTLA4 is also allowed as a prior line of therapy. Study therapy must be initiated within 30 days of previous immune checkpoint blockade therapy (excluding adjuvant anti-PD1 and anti-CTLA4).
Key exclusion criteria (12 listed)
- No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, lobular carcinoma of the breast in situ, atypical melanocytic hyperplasia or melanoma in situ, treated and stable thyroid cancer, adequately treated Stage I cancer (including multiple primary melanomas) from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
- Patients must not currently be on other drugs metabolized by CDA.
- Prior cytotoxic chemotherapy treatment received within 30 days of study enrollment.
- Patients with leptomeningeal disease.
- Current immunosuppressive therapy including >10mg/day of prednisone within 14 days of enrollment is not permitted. Inhaled or topical steroids, and adrenal replacement steroid doses ≤10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral Decitabine/Cedazuridine (DEC-C) in Combination with NivolumabActivation of the RIG-I innate immune pathway and increased expression of tumor antigens and pro-immune genes during Nivolumab treatment may enhance the frequency and activity of anti-tumor immune cells (CD4+ and CD8+ T-cells, NK cells) and reduce the frequency and activity of immunosuppressive cells (MDSCs, Tregs) (1-4), increasing the overall effectiveness and success of Nivolumab treatment. This pilot clinical trial will demonstrate whether combinatorial immunotherapeutic approaches that target epigenetic immune repression and RIG-I activity can favorably alter the tumor immune cell microenvironment and benefit mucosal melanoma patients. | Combination product | Oral Decitabine/Cedazuridine (DEC-C) and Nivolumab in Mucosal Melanoma |
Primary outcome
Determine the safety of DEC-C in combination with Nivolumab unresectable, locally advanced, or metastatic mucosal melanoma patients.
Time frame: 24 months
Determine the safety and tolerability of DEC-C in combination with Nivolumab by evaluating adverse events (AEs) using CTCAEv5.0 criteria and establishing the recommended phase 2 dose (RP2D) of DEC-C.
2 secondary outcomes
Determine the response rate to DEC-C in combination with Nivolumab in unresectable, locally advanced, or metastatic mucosal melanoma patients
Time frame: 24 months
Determine if the addition of DEC-C to Nivolumab increases progression free survival (PFS) and overall survival (OS) in unresectable, locally advanced, or metastatic mucosal melanoma patients.
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Individual participant dataSharing planned: Yes. De-identified data may be shared with the NCCN per research agreement.
Related trials for Malignant Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin McCarter principal investigator
Colorado Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Oral Decitabine/Cedazuridine (DEC-C) in Combination with Nivolumab in people with Malignant Melanoma, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the safety of DEC-C in combination with Nivolumab unresectable, locally advanced, or metastatic mucosal melanoma patients. (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.