Molecularly Redefining Small Bowel Adenocarcinoma to Accelerate Precision Patient Care (SBAMOL)

Small bowel adenocarcinoma is a rare malignancy, and there is limited knowledge about its optimal clinical management and molecular background. The SBAMOL study is an observational biomarker study that aims to identify prognostic and predictive biomarkers. This effort is intended to lay the groundwork for personalized medicine tailored to this specific patient group.

Study Overview

• Status: Recruiting
• Conditions: Small Bowel Adenocarcinoma

Detailed Description

Small bowel adenocarcinoma (SBA), an orphan cancer, has annual diagnoses of 12,070 in the USA and 100 in Denmark. Despite its rarity, patient management should prioritize evidence-based care, but large trials are not feasible, leading to data scarcity and suboptimal care. As a result, SBA is treated like colorectal cancer, yet its prognosis is worse, indicating this parallel approach is insufficient. The grasp on SBAs molecular landscape is limited compared to prevalent cancers. Scant mutational profiling studies, suggest SBA is a heterogeneous disease where subsets resemble other gastrointestinal cancers. This underscores the potential for personalized treatments, including targeted therapies and immunotherapies. Comprehensive molecular characterization, using DNA, RNA, and T-cell receptor characteristics, can provide much-needed strategic direction for patient care and future trials. Capitalizing on this, the investigators propose a comprehensive molecular characterization aiming to develop consensus molecular subtypes that can direct future trials and SBA therapeutic strategies.

The investigators hypothesize that a consensus molecular profiling approach can identify subgroups of SBA with distinct molecular, cellular, and histological characteristics, that will benefit from tailored treatment strategies using chemotherapy, targeted therapy, and immunotherapy.

To explore this hypothesis, the investigators will: (WP1) perform molecular and immunological characterization of tumor tissues from SBA patients (n=200) to establish consensus molecular subtypes of SBA and define their biological attributes; (WP2) ascertain therapeutic avenues tailored to each subtype and devise a molecular algorithm to prospectively categorize individual tumors in real-time, laying the groundwork for molecularly-driven management.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Dan Høgdall, MD PhD; Phone Number: 004538681954; Email: danhog01@regionh.dk
• Study Contact Backup: Name: Jakob HV Schou, MD; Phone Number: 004538682985; Email: jakob.hagen.vasehus.schou@regionh.dk

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Recruiting
    • Department of Oncology, Aarhus University Hospital
    • Contact: Elizaveta M Tabaksblat, MD PhD; Phone Number: 004578450000; Email: eliza.mit.tab@auh.rm.dk
    • Principal Investigator: Elizaveta M Tabaksblat, MD PhD
  • Copenhagen Ø, Denmark, 2100
    • Recruiting
    • Department Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet
    • Contact: Carsten P Hansen, MD DMSc; Phone Number: 004535453545; Email: carsten.palnaes.hansen@regionh.dk
    • Principal Investigator: Carsten P Hansen, MD DMSc
  • Herlev, Denmark, 2730
    • Recruiting
    • Department of Oncology Copenhagen University Hospital - Herlev and Gentofte
    • Contact: Dan Hogdall, MD PhD; Phone Number: 004538681954; Email: danhog01@regionh.dk
    • Principal Investigator: Dan Hogdall, MD PhD
    • Principal Investigator: Jakob HV Schou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with small bowel adenocarcinoma referred to management at participating centers

Description

Inclusion criteria:

Patients with histologically verified small bowel adenocarcinoma Patients older than 18 years

Exclusion criteria:

Insufficient material for molecular testing Patients registered in Vævsanvendelsesregistret&

Vævsanvendelsesregistret; refers to a central Danish registry where patients can opt out of allowing their biological material to be used for purposes other than their own disease management.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular characterization of patients with SBA using high-throughput DNA-, mRNA- and T-cell receptor sequencing and targeted protein expression analyses.	Due to the scarce knowledge of the biological background of SBA. The primary endpoint of the study is to present a comprehensive descriptive molecular characterisation of patients with SBA.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic and predictive DNA biomarkers in patients with SBA	DNA aberrations will associated with disease free, progression free and overall survival. Analysis will be performed using the Oncomine comprehensive plus gene panel. Potential aberrations indicative of targeted treatments will be explored and reported.	5 years
Prognostic and predictive mRNA biomarkers in patients with SBA	mRNA aberrations will associated with disease free, progression free and overall survival. Analysis will be performed using high-throughput sequencing. Potential aberrations indicative of targeted treatments will be explored and reported.	5 years
Prognostic t-cell receptor biomarkers in patients with SBA	T-cell receptor clonality and diversity will associated with disease free, progression free and overall survival. Analysis will be performed using a high-throughput t-cell receptor sequencing.	5 years

Collaborators and Investigators

• Sponsor: Copenhagen University Hospital at Herlev
• Collaborators: Aarhus University Hospital; Rigshospitalet, Denmark; University of Copenhagen
• Investigators: Principal Investigator: Dan Høgdall, MD PhD, Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): December 31, 2033
• Study Completion (Estimated): December 31, 2033

Study Registration Dates

• First Submitted: January 21, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Estimated): January 31, 2024

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: DNA; messenger RNA; Small bowel adenocarcinoma; T-cell receptor sequencing
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: 2312342

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Due to Danish ethical regulations, data can only be shared upon appropriate ethical amendment

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No