MelanomaNCT02694965
Understanding Immunotherapy Resistance Mechanisms in Advanced Melanoma
An observational study of Melanoma, run by Duke University at 1 site in United States.
Trial summary
Purpose of the study: The investigators are proposing that melanomas which respond and develop eventual disease stability in response to checkpoint inhibitor immunotherapy undergo a genetic program promoting secondary resistance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- observational
- Type of treatment
- Injection or infusion
- How many people
- 122 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to 7 Jun 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Arm 1: Eligible patients with stage IV/unresectable stage III melanoma selected to undergo treatment with an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination of an anti-CTLA-4 antibody/anti-PD-1 antibody will be asked to participate in the study by the Principal Investigator, co-Investigators, or clinical staff. Arm 2: 1) Patients either undergoing resection of stage III or stage IV melanoma or have previously undergone resection and who are considered candidates for adjuvant anti-PD-1 antibody immunotherapy. 2) Patients who previously underwent resection of stage III or stage IV melanoma and received prior adjuvant anti-PD-1 antibody immunotherapy and have subsequently developed recurrent melanoma.
Who may be able to join
- Patients with stage III or IV melanoma, with melanoma validated by histology or cytology
- Patients may participate with primary cutaneous melanomas of unknown primary site
- Age ≥ 18 years
- ECOG performance status of 0-2
- Life expectancy of at least 6 months
- Patients with active disease will be treated with either an anti-CTLA-4 antibody , an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination of an anti-CTLA-4 antibody/anti-PD-1 antibody (combined therapy regimens with any other agents are not allowed on this study).
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- Patient must have a measurable systemic lesion defined as greater than or equal to 10 mm based on PET CT/CT/MRI imaging. Pretreatment PET CT/CT imaging must be performed ≤ 42 days prior to treatment initiation ).
- Patients with target skin lesions must equal at least 10 mm when their longest diameters are aggregated. Target skin lesions (5 maximum) must be at least 5 mm in their longest diameter to be considered measurable by caliper or ruler
- Those patients with a failed biopsy attempt or those with disease that is not amenable to biopsy will still be eligible for enrollment and will only undergo blood draws during the study protocol.
- Both men and women of all races and ethnic groups are eligible for this trial.
- Ability to understand and the willingness to sign a written informed consent document
- Patients with intra-cranial disease or disease involving the central nervous system are eligible
- Patients with a current diagnosis of stage III or IV melanoma or a history of stage III or IV melanoma, with melanoma validated by histology or cytology
- Age ≥ 18 years
- ECOG performance status of 0-2
- Patients selected for future adjuvant anti-PD-1 antibody immunotherapy following resection of stage III or stage IV melanoma or patients who received prior adjuvant anti-PD-1 antibody immunotherapy for stage III or IV melanoma and have developed recurrent disease based on physical exam and/or CT/PET CT cross-sectional imaging
- Those patients with a failed biopsy attempt or those with disease that is not amenable to biopsy will still be eligible for enrollment and will only undergo blood draws during the study protocol. Of note, any tissue subjected to prior adjuvant radiation therapy will not be considered for further tissue sampling on this protocol.
- Both men and women of all races and ethnic groups are eligible for this trial.
- Ability to understand and the willingness to sign a written informed consent document
- Patients with intra-cranial disease or disease involving the central nervous system are eligible
Who cannot join
- Patients with a history of a systemic autoimmune disease (eg systemic lupus erythematosus) requiring active therapy
- Patients with a history of another malignancy within the last 5 years except for those patients felt by the treating physician to be cured of that malignancy
- Patients with a diagnosis of a mucosal or ocular melanoma
- Patients who have undergone adjuvant locoregional radiation therapy if less than 4 weeks prior to day of initial biopsy
- Patients who have had prior cytotoxic chemotherapy if less than 6 weeks prior to day of initial biopsy
- Patients who have had prior interferon therapy if less than 4 weeks prior to day of initial biopsy
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- Patients who have had prior anti-CTLA-4 antibody or anti-PD-1 antibody or anti-PD-L1 antibody therapy if less than 4 weeks prior to day of initial biopsy
- Patients who have had prior IL-2 therapy if less than 4 weeks prior to day of initial biopsy
- Patients who have had prior BRAF inhibitor and/or MEK inhibitor therapy if less than 4 weeks prior to day of initial biopsy
- Patients who have received an immunotherapy agent on a previous clinical trial protocol if less than 4 weeks prior to day of initial biopsy
- Patients who are undergoing active steroid therapy if the dose exceeds physiologic steroid doses (equivalent of prednisone 10 mg po daily or less)
- Patients with ongoing or active infection
- Pregnant patients
- Patients with any laboratory test values or serious pre-existing medical condition, that in the opinion of the investigator, makes the patient unsuitable for the study
- Patients unable to comply with the requirements of the study protocol
- Arm 2 Subject Selection:
- The following patients will be asked to participate in the study by the Principal Investigator, co-Investigators, or clinical staff: 1) Patients either undergoing resection of stage III or stage IV melanoma or have previously undergone resection and who are considered candidates for adjuvant anti-PD-1 antibody immunotherapy. 2) Patients who previously underwent resection of stage III or stage IV melanoma and received prior adjuvant anti-PD-1 antibody immunotherapy and have subsequently developed recurrent melanoma.
- Patients with a history of a systemic autoimmune disease (eg systemic lupus erythematosus) requiring active therapy
- Patients with a history of another malignancy within the last 5 years except for those patients felt by the treating physician to be cured of that malignancy
- Patients with a diagnosis of a mucosal or ocular melanoma
- Patients who have had prior cytotoxic chemotherapy if less than 6 weeks prior to day of initial biopsy
- Patients who have undergone adjuvant locoregional radiation therapy if less than 4 weeks prior to day of initial biopsy
- Patients who have had prior interferon therapy if less than 4 weeks prior to day of initial biopsy
- Patients who have had prior anti-CTLA-4 antibody or anti-PD-1 antibody or anti-PD-L1 antibody therapy if less than 4 weeks prior to day of initial biopsy
- Patients who have had prior IL-2 therapy if less than 4 weeks prior to day of initial biopsy
- Patients who have had prior BRAF inhibitor and/or MEK inhibitor therapy if less than 4 weeks prior to day of initial biopsy
- Patients who have received an immunotherapy agent on a previous clinical trial protocol if less than 4 weeks prior to day of initial biopsy
- Patients who are undergoing active steroid therapy if the dose exceeds physiologic steroid doses (equivalent of prednisone 10 mg po daily or less)
- Patients with ongoing or active infection
- Pregnant patients
- Patients with any laboratory test values or serious pre-existing medical condition, that in the opinion of the investigator, makes the patient unsuitable for the study
- Patients unable to comply with the requirements of the study protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Purpose of the study:
The investigators are proposing that melanomas which respond and develop eventual disease stability in response to checkpoint inhibitor immunotherapy undergo a genetic program promoting secondary resistance.
Read the detailed description
Understanding these genetic alterations and the factors which contribute to this process would be critical for the identification of novel immunotherapeutic targets which may synergize with the T cell-targeted checkpoint inhibitors. Furthermore, this work promises to provide greater insight into tumor-mediated immune evasion mechanisms and primary immunotherapy resistance, potentially unveiling predictive markers of clinical response for our expanding arsenal of immune checkpoint inhibitor therapies.
Many patients who exhibit a response to the anti-PD-1 antibodies develop a prolonged course of disease stability which resembles the equilibrium phase of the previously proposed process of cancer immunoediting. This state of equipoise has been hypothesized to involve genetic alterations that promote immune evasion and, in some cases, lead to the development of tumor escape. Based on our data, the investigators propose that melanomas that develop a period of disease stability in response to anti-PD-1 immunotherapy exhibit genetic alterations that suppress the effectiveness of anti-tumor immunity. Our previous studies indicate that the tumor-derived factors that play a role in the paracrine signaling pathways capable of regulating nearby stromal cell populations are more likely to be critical immune regulators of the tumor microenvironment. Therefore, the investigators will focus our studies on those differentially expressed genes which encode soluble proteins using an available prediction algorithm. Those genes identified by this study to be differentially expressed in the melanoma tissues of patients demonstrating a clinical response to immune checkpoint inhibitor therapy will be further evaluated in transgenic autochthonous melanoma models.
- Conditions
- Melanoma
- Being tested
- observational
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
observationalOther
| Study group | Role | What they receive |
|---|---|---|
| Stage IV/Unresectable Stage III Melanoma | Observational - Eligible patients with stage IV/unresectable stage III melanoma selected to undergo treatment with an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination of an anti-CTLA-4 antibody/anti-PD-1 antibody will be asked to participate in the study by the Principal Investigator, co-Investigators, or clinical staff. Receives: Other: observational | |
| Stage III/IV Adjuvant Melanoma | Observational - 1) Patients either undergoing resection of stage III or stage IV melanoma or have previously undergone resection and who are considered candidates for adjuvant anti-PD-1 antibody immunotherapy. 2) Patients who previously underwent resection of stage III or stage IV melanoma and received prior adjuvant anti-PD-1 antibody immunotherapy and have subsequently developed recurrent melanoma. Receives: Other: observational |
What is being measured
The primary outcome is the main question the study is designed to answer.
Observational - Correlate changes in gene expression upon disease progression or recurrence
Arm 1: Differential gene expression will be compared in samples from pre-treatment and disease progression.
Arm 2: Differential gene expression will be compared in samples from pre-treatment and disease recurrence.
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2016 (estimated)
- Study startJan 2016
- Primary completion7 Jun 2023
- Study completion7 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brent Hanks, MD, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02694965
- Sponsor's protocol ID
- Pro00059349
- Status last verified
- Aug 2023
- First submitted
- 18 Feb 2016
- Last updated
- 14 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding Immunotherapy Resistance Mechanisms in Advanced Melanoma
- ClinicalTrials.gov ID
- NCT02694965
- Acronym / sponsor ID
- Pro00059349
- Conditions
- Melanoma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- 7 Jun 2023 (actual)
- Study completion
- 7 Jun 2023 (actual)
- First posted
- 1 Mar 2016 (estimated)
- 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.
Purpose of the study:
The investigators are proposing that melanomas which respond and develop eventual disease stability in response to checkpoint inhibitor immunotherapy undergo a genetic program promoting secondary resistance.
Detailed description
Understanding these genetic alterations and the factors which contribute to this process would be critical for the identification of novel immunotherapeutic targets which may synergize with the T cell-targeted checkpoint inhibitors. Furthermore, this work promises to provide greater insight into tumor-mediated immune evasion mechanisms and primary immunotherapy resistance, potentially unveiling predictive markers of clinical response for our expanding arsenal of immune checkpoint inhibitor therapies.
Many patients who exhibit a response to the anti-PD-1 antibodies develop a prolonged course of disease stability which resembles the equilibrium phase of the previously proposed process of cancer immunoediting. This state of equipoise has been hypothesized to involve genetic alterations that promote immune evasion and, in some cases, lead to the development of tumor escape. Based on our data, the investigators propose that melanomas that develop a period of disease stability in response to anti-PD-1 immunotherapy exhibit genetic alterations that suppress the effectiveness of anti-tumor immunity. Our previous studies indicate that the tumor-derived factors that play a role in the paracrine signaling pathways capable of regulating nearby stromal cell populations are more likely to be critical immune regulators of the tumor microenvironment. Therefore, the investigators will focus our studies on those differentially expressed genes which encode soluble proteins using an available prediction algorithm. Those genes identified by this study to be differentially expressed in the melanoma tissues of patients demonstrating a clinical response to immune checkpoint inhibitor therapy will be further evaluated in transgenic autochthonous melanoma models.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stage IV/Unresectable Stage III Melanoma | – | Other: observationalObservational - Eligible patients with stage IV/unresectable stage III melanoma selected to undergo treatment with an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination of an anti-CTLA-4 antibody/anti-PD-1 antibody will be asked to participate in the study by the Principal Investigator, co-Investigators, or clinical staff. |
| Stage III/IV Adjuvant Melanoma | – | Other: observationalObservational - 1) Patients either undergoing resection of stage III or stage IV melanoma or have previously undergone resection and who are considered candidates for adjuvant anti-PD-1 antibody immunotherapy. 2) Patients who previously underwent resection of stage III or stage IV melanoma and received prior adjuvant anti-PD-1 antibody immunotherapy and have subsequently developed recurrent melanoma. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Arm 1: Eligible patients with stage IV/unresectable stage III melanoma selected to undergo treatment with an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination of an anti-CTLA-4 antibody/anti-PD-1 antibody will be asked to participate in the study by the Principal Investigator, co-Investigators, or clinical staff. Arm 2: 1) Patients either undergoing resection of stage III or stage IV melanoma or have previously undergone resection and who are considered candidates for adjuvant anti-PD-1 antibody immunotherapy. 2) Patients who previously underwent resection of stage III or stage IV melanoma and received prior adjuvant anti-PD-1 antibody immunotherapy and have subsequently developed recurrent melanoma.
Key inclusion criteria (20 listed)
- Patients with stage III or IV melanoma, with melanoma validated by histology or cytology
- Patients may participate with primary cutaneous melanomas of unknown primary site
- Age ≥ 18 years
- ECOG performance status of 0-2
- Life expectancy of at least 6 months
Key exclusion criteria (32 listed)
- Patients with a history of a systemic autoimmune disease (eg systemic lupus erythematosus) requiring active therapy
- Patients with a history of another malignancy within the last 5 years except for those patients felt by the treating physician to be cured of that malignancy
- Patients with a diagnosis of a mucosal or ocular melanoma
- Patients who have undergone adjuvant locoregional radiation therapy if less than 4 weeks prior to day of initial biopsy
- Patients who have had prior cytotoxic chemotherapy if less than 6 weeks prior to day of initial biopsy
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 |
|---|---|---|
| observational | Other | Stage III/IV Adjuvant Melanoma, Stage IV/Unresectable Stage III Melanoma |
Primary outcome
Observational - Correlate changes in gene expression upon disease progression or recurrence
Time frame: up to 3 years
Arm 1: Differential gene expression will be compared in samples from pre-treatment and disease progression. Arm 2: Differential gene expression will be compared in samples from pre-treatment and disease recurrence.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2024.
- Individual participant dataSharing planned: Undecided
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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.
Brent Hanks, MD, PhD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Melanoma, run by Duke University 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 20 inclusion and 32 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 14 Feb 2024. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Observational - Correlate changes in gene expression upon disease progression or recurrence (time frame: up to 3 years). 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 14 Feb 2024.