Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors

• ClinicalTrials.gov Identifier: NCT04871542
• Recruitment Status: Recruiting
• First Posted: May 4, 2021
• Last Update Posted: June 9, 2023
• Sponsor: SWOG Cancer Research Network
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): SWOG Cancer Research Network

Tracking Information

• First Submitted Date: April 29, 2021
• First Posted Date: May 4, 2021
• Last Update Posted Date: June 9, 2023
• Actual Study Start Date: September 13, 2021
• Estimated Primary Completion Date: September 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 29, 2021)

Occurrence of severe or worse non-hematological immune-related adverse event (irAE) [ Time Frame: 52 weeks ]

Adverse events will be recorded according to the physician rated Common Terminology Criteria for Adverse Events (CTCAE) scoring system.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 30, 2021)

• Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 [ Time Frame: Baseline to 52 weeks ]
  PROMIS-29 Includes 4 questions to evaluate each of 7 domains (physical function, anxiety, depression, fatigue, sleep disturbance, social functioning, and pain interference) using a 5- point Likert scale, as well as a single item to assess pain severity on a 0-10 scale. The PROMIS-29 assesses severity levels of symptoms and their effect on the patient's functioning, assessed over the preceding 7-day period.
• Change in PRO-CTCAE scores [ Time Frame: Baseline to 52 weeks ]
  Patients report severity, frequency, and/or interference of toxicities. For this protocol the following 11 items will be assessed: fatigue interference, neuropathy severity and interference, nausea frequency and severity, shortness of breath severity and interference, presence of rash, itching severity, and diarrhea severity and interference over the preceding 7 days.
• Change in PROMIS Cognitive Function- Short Form 4a version 2.0 scores [ Time Frame: Baseline to 52 weeks ]
  Assesses patient-perceived cognitive deficits over the past 7 days. Facets include mental acuity, concentration, verbal and nonverbal memory, verbal fluency, and perceived changes in these cognitive functions. The extent to which cognitive impairments interfere with daily functioning, whether other people observe cognitive impairments, and the impact of cognitive dysfunction on quality of life are also assessed. The PROMIS Short Form Cognitive Function 4a is a questionnaire composed of 4 items rated on a 5 level scale, ranging from Never to Very often (Several times a day), with raw scores ranging from 5 to 20, with higher scores representing better cognitive function. In combination with the PROMIS-29, the use of this questionnaire allows the calculation of the PROMIS-Preference score, which quantifies the value participants place on different health states.
• Change in toxicity over time (ToxT) [ Time Frame: Baseline to 52 weeks ]
  ToxT is a collection of statistical codes in Statistical Analysis Software that generate plots depicting summary statistics or individual patient data over discrete timepoints, combined with longitudinal statistical analyses (repeated measures modelling, and time-to-event and AUC analyses).
• Change in cytokine toxicity (CYTOX) score [ Time Frame: Baseline to 1 cycle after ICI-therapy ]
  The relationship between the CYTOX score and the occurrence of irAE will be evaluated using area under the curve (AUC). Separate evaluations will be conducted using both cytokine levels determined both prior to ICI-based therapy and after 1 cycle of ICI-based therapy.

Original Secondary Outcome Measures (submitted: April 29, 2021)

• Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 [ Time Frame: Baseline to 52 weeks ]
  PROMIS-29 Includes 4 questions to evaluate each of 7 domains (physical function, anxiety, depression, fatigue, sleep disturbance, social functioning, and pain interference) using a 5- point Likert scale, as well as a single item to assess pain severity on a 0-10 scale. The PROMIS-29 assesses severity levels of symptoms and their effect on the patient's functioning, assessed over the preceding 7 day period.
• Change in PRO-CTCAE scores [ Time Frame: Baseline to 52 weeks ]
  Patients report severity, frequency, and/or interference of toxicities; for this protocol the following 11 items will be assessed: fatigue interference, neuropathy severity and interference, nausea frequency and severity, shortness of breath severity and interference, presence of rash, itching severity, and diarrhea severity and interference over the preceding 7 days.
• Change in PROMIS Cognitive Function- Short Form 4a version 2.0 scores [ Time Frame: Baseline to 52 weeks ]
  Assesses patient-perceived cognitive deficits over the past 7 days. Facets include mental acuity, concentration, verbal and nonverbal memory, verbal fluency, and perceived changes in these cognitive functions. The extent to which cognitive impairments interfere with daily functioning, whether other people observe cognitive impairments, and the impact of cognitive dysfunction on quality of life are also assessed. The PROMIS Short Form Cognitive Function 4a is a questionnaire composed of 4 items rated on a 5 level scale, ranging from Never to Very often (Several times a day), with raw scores ranging from 5 to 20, with higher scores representing better cognitive function. In combination with the PROMIS-29, the use of this questionnaire allows the calculation of the PROMIS-Preference score, which quantifies the value participants place on different health states.
• Change in toxicity over time (ToxT) [ Time Frame: Baseline to 52 weeks ]
  ToxT is a collection of statistical codes in Statistical Analysis Software that generate plots depicting summary statistics or individual patient data over discrete timepoints, combined with longitudinal statistical analyses (repeated measures modelling, and time-to-event and AUC analyses).

Current Other Pre-specified Outcome Measures (submitted: August 30, 2021)

Feasibility of the Patient Cloud electronic (e)PRO app [ Time Frame: Up to 52 weeks ]

Will be assessed by comparing the extent of missing data at each assessment time between participants choosing the Patient Cloud ePRO application (app) versus the use of paper forms. The participant experience of using the Patient Cloud ePRO app will also be assessed using a one-time questionnaire at the end of the participant's participation in the study

Original Other Pre-specified Outcome Measures (submitted: April 29, 2021)

Change in cytokine toxicity (CYTOX) score [ Time Frame: Baseline to 1 cycle after ICI-therapy ]

The relationship between the CYTOX score and the occurrence of irAE will be evaluated using area under the curve (AUC). Separate evaluations will be conducted using both cytokine levels determined both prior to ICI-based therapy and after 1 cycle of ICI-based therapy.

Descriptive Information

• Brief Title: Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
• Official Title: Immune Checkpoint Inhibitor Toxicity (I-CHECKIT): A Prospective Observational Study
• Brief Summary: This study examines how certain risk factors (such as age, gender, other medical conditions, and the type of immunotherapy used to treat the cancer) affect whether a patient with a malignant solid tumor will develop mild or serious side effects from the immunotherapy medications. Immunotherapy is the type of treatment that helps the body's immune system fight cancer. In the future, this information may help doctors make better decisions about cancer treatments.

Detailed Description

PRIMARY OBJECTIVE:

I. To both develop and independently validate a risk prediction model for Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher non-hematological immune-related adverse events (irAEs) in the first year of immune checkpoint inhibitor (ICI)-based therapy for the treatment of solid tumors.

SECONDARY OBJECTIVES:

I. To prospectively assess the incidence of any grade of non-hematological irAEs and grade 4 hematological irAEs on ICI-based therapy.

II. To observe the trajectory of patient-reported quality of life and health preferences over 12 months.

III. To observe the trajectory of patient-reported adverse events over 12 months using serial assessment with select Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measures.

IV. To measure the burden of chronic, grade 1 and 2 toxicities using methods such as toxicity over time (ToxT).

V. To track patterns of treatment of irAEs and patterns of toxicity resolution.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To evaluate the cytokine toxicity (CYTOX) score, a composite measure derived from 11 different cytokine levels, both prior to ICI-based therapy and after 1 cycle of ICI-based therapy as a predictive signature for the development of irAEs.

II. To establish a repository of archival tissue and blood/serum specimens for potential predictive and/or prognostic markers of irAE risk.

ADDITIONAL OBJECTIVE:

I. To assess the feasibility of using electronic (e)PRO in a multi-center clinical trial setting.

OUTLINE:

Patients undergo collection of a tissue sample at the start of their routine cancer treatment. Patients complete questionnaires at the start of cancer treatment, weeks 4, 12, 24, and 52. Patients will have the option of providing blood samples at several time points during the study.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Tissue, blood, plasma, buffy coat

• Sampling Method: Non-Probability Sample
• Study Population: Patients planning to receive ICI-based therapy for a solid tumor malignancy.
• Condition: Malignant Solid Neoplasm

Intervention

• Procedure: Biospecimen Collection
  Undergo collection of blood sample
  Other Name: Biological Sample Collection
• Other: Questionnaire Administration
  Complete questionnaires

Study Groups/Cohorts

Observational (biospecimen collection, questionnaire)

Patients undergo collection of a tissue sample at the start of their routine cancer treatment. Patients complete questionnaires at the start of cancer treatment, weeks 4, 12, 24, and 52. Patients will have the option of providing blood samples at several time points during the study.

Interventions:

• Procedure: Biospecimen Collection
• Other: Questionnaire Administration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 29, 2021): 2062
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2026
• Estimated Primary Completion Date: September 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants must be planning to receive ICI-based therapy for a solid tumor malignancy. This therapy must be given according to Food and Drug Administration (FDA) label or National Comprehensive Cancer Network (NCCN) guidelines at Category 1 or 2A and not in the context of a clinical trial
• Participants who have received prior ICI-based therapy must have completed ICI based therapy at least 180 days prior to registration
• Participants must not have discontinued any prior ICI-based therapy (if applicable) because of irAE
• Participants must not have received chemotherapy, biologic, or targeted-therapy within 21 days prior to registration

• Participants must have recovered from side effects of prior therapy to the following standards per treating physician's discretion:

  • =< Grade 1 for any non-hematologic side effects (excluding neuropathy and alopecia); lab-related parameters of liver and renal function will be considered at the discretion of the treating physician)
  • =< Grade 2 for neuropathy and/or alopecia
  • Grade 3 or less for any hematologic side effects
• Participants must be planning to begin standard of care ICI-based therapy within 3 calendar days after registration
• Participants must not be planning to receive ICI-based therapy in combination with chemotherapy or any other non-ICI therapy for treatment of their cancer
• Participants must be at least 18 years of age
• Participants must complete their history and physical examination within 28 days prior to registration
• Participants who can complete the S2013 Feasibility Questionnaire in English or Spanish must participate at the scheduled assessments
• Participants must be able to complete Patient-Reported Outcome (PRO) instruments in English, Spanish, or French and must be planning to complete PROs at all scheduled assessments
• Participants must complete the pre-registration (baseline) PRO forms within 14 days prior to registration

• Participants must be willing to participate in PRO data collection

  • Note: Prior to registration, participants must decide on their method (paper or electronic) of completing their follow-up questionnaires. Participants who elect electronic (ePRO) completion must have an iPhone, Android phone, or tablet with cellular or WiFi connectivity in order to download the Patient Cloud mobile applications onto the device (personal device or a site provisioned device for multi-users)
• Participants must be offered the opportunity to participate in the optional specimen banking

• Note: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

  • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04871542
• Other Study ID Numbers: S2013; NCI-2021-01262 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); S2013 ( Other Identifier: SWOG ); SWOG-S2013 ( Other Identifier: DCP ); S2013 ( Other Identifier: CTEP ); UG1CA189974 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: SWOG Cancer Research Network
• Original Responsible Party: Same as current
• Current Study Sponsor: SWOG Cancer Research Network
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Krishna S Gunturu; SWOG Cancer Research Network

• PRS Account: SWOG Cancer Research Network
• Verification Date: June 2023