Immune Related Toxicity and Symptom Burden in Chronic Cancer Survivors With Melanoma Receiving Adjuvant Immunotherapy With Immune Checkpoint Inhibitors

Recruiting

• Conditions: Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Melanoma, Stage II; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Clinical Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Melanoma Stage IV
• Interventions: Behavioral: Assessment; Procedure: Biospecimen Collection; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

• Registration Number: NCT04990726
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

This study evaluates the immune related toxicity and symptom burden in chronic cancer survivors with melanoma who are receiving adjuvant immunotherapy with immune checkpoint inhibitors. Information collected in this study may help doctors to learn more about the side effects caused by immunotherapy, and to learn if there are any relationships between these side effects and immune and genetic biomarkers found in the blood that may be related to patient's reaction to immunotherapy.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the detailed clinical characterization including timing, severity, and phenotype of immune related adverse events (irAEs) in chronic survivors with melanoma from initiation of adjuvant checkpoint inhibitors (CPI) therapy through 24 months of follow-up.

II. Longitudinally assess patients-reported outcomes (PROs) that measure symptom burden (such as fatigue, depression, sleep disturbance) and quality of life (QOL) in those patients, compared to patients with similar disease stage who opt for active surveillance.

SECONDARY OBJECTIVES:

I. Longitudinally evaluate the correlation of changes in immune analysis (immune cells and cytokines) in peripheral blood samples with timing, severity, and phenotype of irAEs, symptom burden, and QOL in those patients, compared to patients with similar disease stage who opt for active surveillance.

II. Determine whether specific immune-related genetic polymorphisms are associated with the development of irAEs and symptom burden in melanoma patients receiving adjuvant CPI therapy.

OUTLINE:

Patients undergo medical assessments and blood sample collection, and complete questionnaires at baseline, 1 (optional), 3, 6, 12, 18, and 24 months.

Study Timeline

• Study Start: 2019-12-05
• Study First Submitted: 2021-02-11
• Study First Submitted QC: 2021-07-27
• Study First Posted: 2021-08-04
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-26
• Last Update Posted: 2024-08-27
• Primary Completion: 2027-02-02
• Study Completion: 2027-02-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 275

Inclusion Criteria

• Age >= 18 years of age
• Surgically resected stage II, III, or IV melanoma with no evidence of disease according to the American Joint Committee on Cancer (AJCC) classification criteria
• Eligible for adjuvant CPI treatment per treating physician discretion
• Plan to continue care at MD Anderson Cancer Center (MDACC)
• Ability to communicate and read in English language

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Exclusion Criteria

• Previous systemic therapy for melanoma

• Previous history of other cancers treated with immunotherapy

  • Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
  • Previous cancer that has been resected two or more years ago are not excluded.

• Previous history of inflammatory or autoimmune diseases. This include but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or psoriasis. Patients with autoimmune thyroid disease, vitiligo, and type I diabetes mellitus are not excluded.

• Other concurrent malignancies that require active therapy

• Participants < 18 years of age and pregnant women are not eligible to participate in this study

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Observational (assessment, blood collection, questionnaire)	Assessment	Patients undergo medical assessments and blood sample collection and complete questionnaires at baseline, 1, 3, 6, 12, 18, and 24 months.
Observational (assessment, blood collection, questionnaire)	Biospecimen Collection	Patients undergo medical assessments and blood sample collection and complete questionnaires at baseline, 1, 3, 6, 12, 18, and 24 months.
Observational (assessment, blood collection, questionnaire)	Quality-of-Life Assessment	Patients undergo medical assessments and blood sample collection and complete questionnaires at baseline, 1, 3, 6, 12, 18, and 24 months.
Observational (assessment, blood collection, questionnaire)	Questionnaire Administration	Patients undergo medical assessments and blood sample collection and complete questionnaires at baseline, 1, 3, 6, 12, 18, and 24 months.
Treatment (assessment, blood collection, questionnaire)	Assessment	Patients undergo medical assessments and blood sample collection and complete questionnaires at baseline (prior to C1 infusion), 2, 4, 7 infusion, at end of treatment, and 18 and 24 months after completion of treatment.
Treatment (assessment, blood collection, questionnaire)	Biospecimen Collection	Patients undergo medical assessments and blood sample collection and complete questionnaires at baseline (prior to C1 infusion), 2, 4, 7 infusion, at end of treatment, and 18 and 24 months after completion of treatment.
Treatment (assessment, blood collection, questionnaire)	Quality-of-Life Assessment	Patients undergo medical assessments and blood sample collection and complete questionnaires at baseline (prior to C1 infusion), 2, 4, 7 infusion, at end of treatment, and 18 and 24 months after completion of treatment.
Treatment (assessment, blood collection, questionnaire)	Questionnaire Administration	Patients undergo medical assessments and blood sample collection and complete questionnaires at baseline (prior to C1 infusion), 2, 4, 7 infusion, at end of treatment, and 18 and 24 months after completion of treatment.

Primary Outcome Measures

Name	Time	Method
Detailed clinical characterization	24 months	Will determine the detailed clinical characterization including timing, severity, and phenotype of immune related adverse events (irAEs) in chronic survivors with melanoma from initiation of adjuvant checkpoint inhibitor (CPI) therapy through 24 months of follow-up. The primary end point will be at 12 months, but patients will be followed for up to 24 months. Will estimate the incidence rates of any de novo grade 2 or higher irAEs at 12 months post treatment initiation along with 95% confidence interval within the case group. Will also summary irAEs by their onset time in relation to treatment initiation (acute irAE vs late irAE) and by CPI type. Descriptive statistics will be used to summarize results.
Patients-reported outcomes (PROs)	24 months	Will compare PROs at 12 months between the case (with and without irAEs) and control groups. To compare differences between cases and controls, will use logistic regression to adjust for age, gender, ethnicity, tumor stage and type of CPI therapy. The primary outcome measures include quality of life, depression, and fatigue. Will compare each of the three primary outcomes at a significant level of 0.017 (0.05/3) using Bonferroni multiple comparison adjustment. Will use linear mixed effect models to fit the longitudinal PRO assessments to study the change of PROs over time taking the intra-patient correlation into account and to determine the effect of each of the covariates (relevant patient's demographic, irAEs, clinical and treatment characteristics) on the outcomes.

Secondary Outcome Measures

Name	Time	Method
Immune-related genetic polymorphisms	24 months	Will determine whether specific immune-related genetic polymorphisms are associated with the development of irAEs and symptom burden in melanoma patients receiving adjuvant CPI therapy.
Changes in immune analysis	24 months	Will longitudinally evaluate the correlation of changes in immune analysis in peripheral blood samples with timing, severity, and phenotype of irAEs, symptom burden, and quality of life in those patients, compared to patients with similar disease stage who opt for active surveillance.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States