Understanding Immunotherapy Resistance Mechanisms in Advanced Melanoma

NCT02694965 | Completed

• 1 other identifier: Pro00059349
• Study Type: observational
• Target: 122
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• 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.

  up to 3 years

Study Arms (2)

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.

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.

Other: observational

Interventions

observational OTHER

Stage III/IV Adjuvant Melanoma; Stage IV/Unresectable Stage III Melanoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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).
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Low risk biopsy and blood samples

MeSH Terms

Conditions

Melanoma

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Brent Hanks, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2016
• First Posted: March 1, 2016
• Study Start: January 1, 2016
• Primary Completion: June 7, 2023
• Study Completion: June 7, 2023
• Last Updated: February 14, 2024

Record last verified: 2023-08

Locations

US (1)