Longitudinal Multimodal Response Assessment During Neoadjuvant Treatment of Rectal Cancer (PRIMO)

Planning Adaptive Treatment by Longitudinal Response Assessment Implementing MR Imaging, Liquid Biopsy and Analysis of Microenvironment During Neoadjuvant Treatment of Rectal Cancer (PRIMO)

This pilot study aims to trial multimodal early response assessment to enable therapy adaptions in the context of non-operative therapy strategies of locally advanced rectal cancer (LARC) for development of a non-invasive response prediction model.

Study Overview

• Status: Active, not recruiting
• Conditions: Radiotherapy; Neoadjuvant Treatment; Locally Advanced Rectal Carcinoma; Adaptive Treatment
• Intervention / Treatment: Diagnostic test: Blood sample; Device: MRI scan

Detailed Description

Patients with LARC, receiving neoadjuvant chemoradiotherapy (CRT) are followed by at least 4 multiparametric MRI-scans (diffusion weighted imaging and hypoxia-sensitive sequences) as well as repeated blood samples in order to analyse circulating tumour cells (CTCs). A standard pelvis radiotherapy (RT, 5040 cGy) will be performed in combination with a 5-Fluorouracil / Oxaliplatin regimen in all patients (planned: N = 50), succeeded by consolidation CTx (FOLFOX4) if feasible. Additional histologic markers, such as tumour-infiltrating lymphocytes (TILs) or PD-L1 status will be analysed before and after CRT. Resection is standard after completion of preoperative treatment. In case of complete regression and patient's request, a non-operative management ("watch and wait") is offered alternatively. The primary endpoint is response, defined by tumor regression grading, secondary endpoints comprise longitudinal changes in MRI as well as in CTCs and TILs.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

Study Locations

• Germany
  • Jena, Germany
    • Department of Radiotherapy and Radiation Oncology, Jena University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with locally advanced rectal cancer (LARC), receiving neoadjuvant chemoradiotherapy (CRT).

Description

Inclusion Criteria:

• locally advanced rectal cancer (LARC): UICC Stage II/III
• no severe cardiac or lung disease
• no severe hepatic disorders (liver enzymes <2.5 NR) or restrictions of renal function (GFR > 30ml/min)
• no severe cytopenia (Neutrocytes >= 3 Gpt/l; Thrombocytes >= 100 Gpt/l; Hemoglobin >6mmol/l)
• no homozygotic DPD deficiency
• no other neoplasms requiring therapy
• no earlier radiotherapy of the pelvis or earlier chemotherapy
• no contraindications for MRI

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor regression grading (TRG)	Histological response assessment by TRG (Werner / Hoefler et al.); Complete response is defined as TRG 1a;	after completion of neoadjuvant treatment (up to 10 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	overall survival	5 years
MRI	longitudinal changes in multiparametric MRI sequences (diffusion weighted and hypoxia sensitive)	up to 10 months, until resection
Circulating Tumor Cells (CTC)	longitudinal changes in CTCs	5 years
Tumor Infiltrating Lymphocytes (TIL)	longitudinal changes in TILs	up to 10 months, until resection
PFS	progression free survival	5 years
Surrogate marker: Interleukin 6 (IL-6)	surrogates of tumor and inflammation from routine blood draws [ng/l]	5 years
Surrogate marker: Carcinoembryonic Antigen (CEA)	surrogates of tumor and inflammation from routine blood draws, [mg/l]	5 years

Collaborators and Investigators

• Sponsor: Jena University Hospital
• Investigators: Principal Investigator: Andrea Wittig-Sauerwein, MD, Department for Radiotherapy and Radiooncology, Jena University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2022
• Primary Completion (Estimated): January 31, 2026
• Study Completion (Estimated): September 30, 2030

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 1, 2022

Study Record Updates

• Last Update Posted (Estimated): September 8, 2025
• Last Update Submitted That Met QC Criteria: August 31, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: rectal cancer; circulating tumor cells; liquid biopsy; DWI; tumor infiltrating lymphocytes; organ preservation; total neoadjuvant therapy (TNT); T2* MRI
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Neoplasm Metastasis; Pathological Conditions, Signs and Symptoms; Rectal Neoplasms; Neoplastic Cells, Circulating; Investigative Techniques; Therapeutics; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Tomography; Diagnostic Imaging; Blood Specimen Collection; Magnetic Resonance Imaging; Phlebotomy
• Other Study ID Numbers: UKJ-PRIMO-2022; CSP-11 (Other Grant/Funding Number: Clinician Scientist Program, Interdisciplinary Center for Clinical Research, Jena University Hospital); LIFE Talent Funds 2022 (Other Grant/Funding Number: Friedrich Schiller University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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