MelanomaPhase 2NCT02403778
Ipilimumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma
A Phase 2 study testing VESANOID and Ipilimumab in people with Melanoma, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The purpose of this study is to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients. Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Melanoma
- What is being tested?
- VESANOID and Ipilimumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Dec 2015to 18 Jan 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients over the age of 18 year.
- Patients diagnosed with advanced melanoma.
- Patients that are considered candidates for ipilimumab therapy.
- Patients able to understand and willing to sign a written informed consent documents.
- Patients willing to have regular blood draws, one before treatment and four during or after treatment.
Who cannot join
- Patients under the age of 18.
- Patients with Stage I or II, melanoma who are not candidates for Ipilimumab.
- Patients that have received systemic treatments within four weeks prior to the beginning of treatment.
- Women that are pregnant or nursing.
- Patients taking immunosuppressive medications.
- Patients with active autoimmune disease.
- Patients with known sensitivity to retinoic acid derivatives.
- Patients with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin > 2.5 × ULN.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Hospital
Aurora, Colorado, 80045
About this study
The purpose of this study is to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients.
Read the detailed description
The successful treatment of melanoma with immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1) antibodies, has altered our thinking and approach to immunotherapy for solid tumors. Despite these advances, only a portion of patients experience a durable response suggesting that there is room for improvement via enhanced immunomodulatory approaches. Anti-CTLA-4 (Ipilimumab) significantly improves overall survival and achieves long-lasting complete responses in some melanoma patients, the number of patients that achieve durable clinical benefit is limited and could be improved by a combined immunomodulatory approach. The objectives of this study are to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients. We hypothesize that combined treatment with Ipilimumab and ATRA will improve patient responses, increase tumor antigen-specific T cell responses, and decrease immunosuppressive myeloid-derived suppressor cells (MDSCs) in melanoma patients compared to patients treated with Ipilimumab alone.
- Conditions
- Melanoma
- Being tested
- VESANOID, Ipilimumab
- Keywords
- Melanoma, Malignant Melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VESANOIDDrug
Also called ATRA, Tretinoin
All-trans retinoic acid (ATRA) is a vitamin A derivative that binds the retinoic acid receptor on MDSCs and differentiates immature monocytes into more mature dendritic cells (12). VESANOID is a standard treatment for patients with acute promyelocytic leukemia (APL).
IpilimumabDrug
Also called IPI
Ipilimumab is current standard of care treatment for melanoma.
| Study group | Role | What they receive |
|---|---|---|
| Ipilimumab | Active comparator | Arm A (No VESANOIDTherapy) will receive the standard of care treatment with ipilimumab only, receiving the standard 4 doses of either 3 or 10 mg/kg ipilimumab every 3 weeks. Receives: Drug: Ipilimumab |
| VESANOID | Experimental | Arm B (VESANOID Therapy) will receive the standard 4 doses of either 3 or 10 mg/kg ipilimumab every three weeks plus the supplemental treatment of 150 mg/m2 of VESANOID orally for 3 days surrounding each dose of ipilimumab (day -1, day 0, day +1) for a total of 12 days of VESANOID treatment. Receives: Drug: VESANOID; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Adverse Events
Safety and tolerability of ipilimumab and VESANOID combination therapy in advanced melanoma patients will be established using the Bayesian approach.
Measured: Up to 2 years from the time of study enrollment for each patient.
MDSC Frequency
The frequency of circulating MDSCs will be measured by flow cytometry and calculated as a percentage of the total myeloid cell population. This outcome will be measured at the final study blood draw between 84 and 130 days following the first treatment.
Measured: 84 and 130 days following the first treatment
MDSC Suppressive Function
MDSC suppressive function in peripheral blood will be measured through the activation and proliferation of T cells in the presence of isolated MDSCs. Functional assays will be performed to assess the ability of isolated MDSCs to suppress T-cell responses.
Measured: 4 weeks prior to start, Midway thru and at least 30 days post final infusion
Secondary outcomes (2)
Changes in the Frequency of Tumor-specific T Cell Responses
Changes in the frequency of tumor-specific T cell responses attributable to the addition of VESANOID to standard ipilimumab therapy will be determined by the frequency of Interferons (IFN)-gamma producing cells after stimulation with melanoma antigens.
Measured: 4 weeks prior to start, Midway thru and at least 30 days post final infusion
Unresectable Stage III and STAGE IV
Subjects will be followed for evidence of disease progression.
Measured: Up to 2 years from the time of study enrollment for each patient.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2015 (estimated)
- Study start17 Dec 2015
- Primary completionAug 2018
- Study completion18 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Martin McCarter, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02403778
- Sponsor's protocol ID
- 14-0948.cc
- Status last verified
- Sep 2023
- First submitted
- 23 Feb 2015
- Last updated
- 21 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Tobin RP, Jordan KR, Robinson WA, Davis D, Borges VF, Gonzalez R, Lewis KD, McCarter MD. Targeting myeloid-derived suppressor cells using all-trans retinoic acid in melanoma patients treated with Ipilimumab. Int Immunopharmacol. 2018 Oct;63:282-291. doi: 10.1016/j.intimp.2018.08.007. Epub 2018 Aug 16.
PubMed 30121453
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ipilimumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma
- ClinicalTrials.gov ID
- NCT02403778
- Acronym / sponsor ID
- 14-0948.cc
- Conditions
- Melanoma
- Keywords
- Melanoma, Malignant Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 17 Dec 2015 (actual)
- Primary completion
- Aug 2018 (actual)
- Study completion
- 18 Jan 2023 (actual)
- First posted
- 31 Mar 2015 (estimated)
- Results
- Posted 16 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients.
Detailed description
The successful treatment of melanoma with immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1) antibodies, has altered our thinking and approach to immunotherapy for solid tumors. Despite these advances, only a portion of patients experience a durable response suggesting that there is room for improvement via enhanced immunomodulatory approaches. Anti-CTLA-4 (Ipilimumab) significantly improves overall survival and achieves long-lasting complete responses in some melanoma patients, the number of patients that achieve durable clinical benefit is limited and could be improved by a combined immunomodulatory approach. The objectives of this study are to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients. We hypothesize that combined treatment with Ipilimumab and ATRA will improve patient responses, increase tumor antigen-specific T cell responses, and decrease immunosuppressive myeloid-derived suppressor cells (MDSCs) in melanoma patients compared to patients treated with Ipilimumab alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ipilimumab | Active comparator | Drug: IpilimumabArm A (No VESANOIDTherapy) will receive the standard of care treatment with ipilimumab only, receiving the standard 4 doses of either 3 or 10 mg/kg ipilimumab every 3 weeks. |
| VESANOID | Experimental | Drug: VESANOID, Drug: IpilimumabArm B (VESANOID Therapy) will receive the standard 4 doses of either 3 or 10 mg/kg ipilimumab every three weeks plus the supplemental treatment of 150 mg/m2 of VESANOID orally for 3 days surrounding each dose of ipilimumab (day -1, day 0, day +1) for a total of 12 days of VESANOID treatment. |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients over the age of 18 year.
- Patients diagnosed with advanced melanoma.
- Patients that are considered candidates for ipilimumab therapy.
- Patients able to understand and willing to sign a written informed consent documents.
- Patients willing to have regular blood draws, one before treatment and four during or after treatment.
Key exclusion criteria (8 listed)
- Patients under the age of 18.
- Patients with Stage I or II, melanoma who are not candidates for Ipilimumab.
- Patients that have received systemic treatments within four weeks prior to the beginning of treatment.
- Women that are pregnant or nursing.
- Patients taking immunosuppressive medications.
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 |
|---|---|---|
| VESANOIDAlso: ATRA, TretinoinAll-trans retinoic acid (ATRA) is a vitamin A derivative that binds the retinoic acid receptor on MDSCs and differentiates immature monocytes into more mature dendritic cells (12). VESANOID is a standard treatment for patients with acute promyelocytic leukemia (APL). | Drug | VESANOID |
| IpilimumabAlso: IPIIpilimumab is current standard of care treatment for melanoma. | Drug | Ipilimumab, VESANOID |
Primary outcome
Number of Adverse Events
Time frame: Up to 2 years from the time of study enrollment for each patient.
Safety and tolerability of ipilimumab and VESANOID combination therapy in advanced melanoma patients will be established using the Bayesian approach.
MDSC Frequency
Time frame: 84 and 130 days following the first treatment
The frequency of circulating MDSCs will be measured by flow cytometry and calculated as a percentage of the total myeloid cell population. This outcome will be measured at the final study blood draw between 84 and 130 days following the first treatment.
MDSC Suppressive Function
Time frame: 4 weeks prior to start, Midway thru and at least 30 days post final infusion
MDSC suppressive function in peripheral blood will be measured through the activation and proliferation of T cells in the presence of isolated MDSCs. Functional assays will be performed to assess the ability of isolated MDSCs to suppress T-cell responses.
2 secondary outcomes
Changes in the Frequency of Tumor-specific T Cell Responses
Time frame: 4 weeks prior to start, Midway thru and at least 30 days post final infusion
Unresectable Stage III and STAGE IV
Time frame: Up to 2 years from the time of study enrollment for each patient.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30121453Tobin RP, Jordan KR, Robinson WA, Davis D, Borges VF, Gonzalez R, Lewis KD, McCarter MD. Targeting myeloid-derived suppressor cells using all-trans retinoic acid in melanoma patients treated with Ipilimumab. Int Immunopharmacol. 2018 Oct;63:282-291. doi: 10.1016/j.intimp.2018.08.007. Epub 2018 Aug 16.
- Individual participant dataSharing planned: No
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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, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VESANOID and Ipilimumab in people with 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 5 inclusion and 8 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: finished, as of the sponsor's last update on 21 Sep 2023. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 16 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Adverse Events (time frame: Up to 2 years from the time of study enrollment for each patient.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02403778, which also lists 1 linked publication.
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 21 Sep 2023.