Longitudinal Multimodal Response Assessment During Neoadjuvant Treatment of Rectal Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Locally Advanced Rectal Carcinoma, Neoadjuvant Treatment, Radiotherapy, Adaptive Treatment

Intervention / Treatment
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* Diagnostic Test: Blood sample
* Device: MRI scan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Blood sample|longitudinal blood samples for CTC monitoring|
|Device: MRI scan|longitudinal MRI scans (non-contrast enhanced)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor regression grading (TRG) | Histological response assessment by TRG (Werner / Hoefler et al.); Response is defined as TRG 1a/b/2; | after completion of neoadjuvant treatment (up to 10 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| OS | overall 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DWI, total neoadjuvant therapy (TNT), T2* MRI, circulating tumor cells, tumor infiltrating lymphocytes, liquid biopsy, rectal cancer, organ preservation