Sepsis in Oncology Patients (SEPONC)

• ClinicalTrials.gov Identifier: NCT06046677
• Recruitment Status: Not yet recruiting
• First Posted: September 21, 2023
• Last Update Posted: September 21, 2023
• Sponsor: Royal Marsden NHS Foundation Trust
• Information provided by (Responsible Party): Royal Marsden NHS Foundation Trust

Tracking Information

• First Submitted Date: June 8, 2023
• First Posted Date: September 21, 2023
• Last Update Posted Date: September 21, 2023
• Estimated Study Start Date: September 2023
• Estimated Primary Completion Date: September 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 13, 2023)

• Identification of circulating leukocyte transcriptomic phenotypes relating to mortality in sepsis patients with a background of cancer, (in comparison to those previously identified in non-immunosuppressed patients). [ Time Frame: end of trial (4 years) ]
  Identification of circulating leukocyte transcriptomic phenotypes relating to mortality in sepsis patients with a background of cancer, (in comparison to those previously identified in non-immunosuppressed patients).
• 28 day mortality [ Time Frame: end of recruitment (3 years) ]
  28 day mortality

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: September 13, 2023)

• Differences in the trajectory of transcriptomic phenotypes of patients admitted to ICU with sepsis, and how they relate to severity scorings and mortality/morbidity outcomes [ Time Frame: end of trial (4 years) ]
  how they relate to severity scorings and mortality/morbidity outcomes
• Differences in the trajectory of functional phenotypes of patients admitted to ICU with sepsis, and how they relate to severity scorings and mortality/morbidity outcomes [ Time Frame: end of trial (4 years) ]
  how they relate to severity scorings and mortality/morbidity outcomes
• Differences in the trajectory of genomic phenotypes of patients admitted to ICU with sepsis, and how they relate to severity scorings and mortality/morbidity outcomes [ Time Frame: end of trial (4 years) ]
  how they relate to severity scorings and mortality/morbidity outcomes
• Identification of differences in transcriptomic phenotypes between patient subgroups and on comparison to non-immunosuppressed sepsis patients. Comparison in length of stay measures and quality of life parameters [ Time Frame: end of trial (4 years) ]
  Comparison in length of stay measures and quality of life parameters
• Identification of differences in functional phenotypes between patient subgroups and on comparison to non-immunosuppressed sepsis patients. Comparison in length of stay measures and quality of life parameters [ Time Frame: end of trial (4 years) ]
  Comparison in length of stay measures and quality of life parameters
• Identification of differences in genomic phenotypes between patient subgroups and on comparison to non-immunosuppressed sepsis patients. Comparison in length of stay measures and quality of life parameters [ Time Frame: end of trial (4 years) ]
  Comparison in length of stay measures and quality of life parameters

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sepsis in Oncology Patients
• Official Title: Investigation Into the Transcriptomic and Functional Profile of SEPsis in ONCology Patients

Brief Summary

The overall objective of this prospective observational study is to address the significant knowledge gap that exists around the impact of immune dysfunction on the development and survival from sepsis in patients with cancer. This proposal primarily focuses on establishing the transcriptomic immune profiles of sepsis patients with a background of cancer. This analysis will be complemented with in vitro functional analyses, and in addition will commence a collection of genome-wide data, including a focus on predicting white cell number and function in health. Uniquely, the investigators propose to establish a robust link between these analyses: transcriptomic, in vitro, and genome-wide, to enable them to comprehensively explore septic oncology patient 'immune phenotypes' and effectively identify novel exploitable therapeutic pathways.

To this end, this project will collect, analyse and/or sequence DNA, RNA, leukocytes and soluble materials from a cohort of oncology patients presenting to intensive care with sepsis. This cohort will include all-comers with an oncological background but will also focus on two core groups at high risk of sepsis where baseline samples can also be sought prior to major immunosuppressive events in the cancer pathway. These are:

1. Oesophageal/upper gastrointestinal (GI) cancer patients prior to systemic anticancer therapy initiation or surgery
2. Haematological malignancy patients prior to stem cell transplantation.

These sub-cohorts will provide a previously unexplored unique insight into the role of pre-existing patient transcriptomic phenotypes.

Detailed Description

The specific aims will be to perform multi-modal parallel immune phenotyping to determine:

• The transcriptomic (RNA) phenotypes (or 'signatures') of cancer patients with sepsis

• The association of these transcriptomic phenotypes with:

  1. Leukocyte function in sepsis, as quantified by cell surface and functional assays and plasma soluble mediator content
  2. Pre-existing genomic determinants such as leukocyte numbers
  3. Severity of, and outcome from, sepsis in oncology patients

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

Biospecimen

Retention:   Samples With DNA

Description:

Buffy coat & PMBCs PAXgene RNA Plasma

• Sampling Method: Non-Probability Sample

Study Population

Patients who develop sepsis on ICU or require admission to ICU with sepsis will be identified and screened for enrolment by the research team at the Royal Marsden NHS Foundation Trust

Elective pre-operative upper GI surgical patients or elective stem cell transplant patients will be consented and enrolled at baseline, immediately prior to these procedures.

• Condition: Sepsis in Cancer Patients

Intervention

Other: No intervention

No intervention

Study Groups/Cohorts

• Sepsis cohort

  Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.

  Organ dysfunction can be identified as an acute change in total SOFA score ≥2 points consequent to the infection.

  Intervention: Other: No intervention
• Elective cohort
  Elective pre-operative upper GI surgical patients or elective stem cell transplant patients will be consented and enrolled at baseline, immediately prior to these procedures. If they go on to develop sepsis within 60 days of their surgery, they will go on to be sampled as per the sepsis cohort
  Intervention: Other: No intervention

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: September 13, 2023): 180
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2027
• Estimated Primary Completion Date: September 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Sepsis cohort: Inclusion Criteria:

• Patients admitted to ICU with a diagnosis of sepsis as per 'Sepsis-3' definitions with a SOFA score [REF] ≥2 secondary to infection from any source
• ≥18 years of age
• Written consent from patient, personal or professional consultee, or deferred consent if none of the above available at admission

Sepsis cohort Exclusion Criteria:

• Death deemed imminent by the clinical team

Elective cohort inclusion criteria

• Patients undergoing elective major upper GI surgery (oesophago+/-gastrectomy) or stem cell transplant for haematological malignancy
• ≥18 years of age
• Written consent from patient

Elective cohort exclusion criteria

• Limitations in place regarding provision of treatment and/or organ support e.g., palliative patients

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Not Provided
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT06046677
• Other Study ID Numbers: CCR5669
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Royal Marsden NHS Foundation Trust
• Original Responsible Party: Same as current
• Current Study Sponsor: Royal Marsden NHS Foundation Trust
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Royal Marsden NHS Foundation Trust
• Verification Date: September 2023