Understanding Immunotherapy Resistance Mechanisms in Advanced Melanoma
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|ClinicalTrials.gov Identifier: NCT02694965|
Recruitment Status : Suspended (COVID-19; enrollment will resume when local guidance is updated)
First Posted : March 1, 2016
Last Update Posted : May 14, 2020
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.
|Condition or disease||Intervention/treatment|
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 Type :||Observational|
|Estimated Enrollment :||100 participants|
|Official Title:||Understanding Immunotherapy Resistance Mechanisms in Advanced Melanoma|
|Study Start Date :||January 2016|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||July 2021|
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.
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.
- 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.
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02694965
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Brent Hanks, MD, PhD||Duke University|