Neoplasms

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Carcinoma

Neoplastic Cells, Circulating

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

longitudinal blood samples for CTC monitoring

Blood sample

longitudinal MRI scans (non-contrast enhanced)

MRI scan

Georg Wurschi, MD

Andrea Wittig-Sauerwein, MD

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.

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.

* histological analysis of tumor specimens (pre-treatment biopsy and resected tumor)
* blood samples (Circulating Tumor Cells, CTCs)

Longitudinal Multimodal Response Assessment During Neoadjuvant Treatment of Rectal Cancer

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

Histological response assessment by TRG (Werner / Hoefler et al.); Response is defined as TRG 1a/b/2;

longitudinal changes in multiparametric MRI sequences (diffusion weighted and hypoxia sensitive)

surrogates of tumor and inflammation from routine blood draws \[ng/l\]

surrogates of tumor and inflammation from routine blood draws, \[mg/l\]

Jena University Hospital

Principal Investigator

Nervous System Diseases

Syncope

Neoplasm Metastasis

Antineoplastic Agents

All Drugs and Chemicals

Oxaliplatin

Capecitabine

Short radiotherapy (5X5 Gy) and capecitabine/oxaliplatin

Total neoadjuvant therapy (TNT)

Postoperative MRD on circulating cell-free DNA

Minimal residual disease (MRD)

Long-course 50.4 Gy radiation with capecitabine

Long radiation therapy

Toni T Seppala, MD, PhD

Toni Seppala, Prof

Rectal cancer represents the most complex area of multidisciplinary treatment in bowel surgery. In 2017, there were 1221 new rectal cancers in Finland. The prognosis of colorectal cancer (CRC) patients these days is almost exclusively driven by the occurrence of the metastatic form of the disease.

The treatment of rectal cancer often includes a long delay between diagnosis and the initiation of systemic chemotherapy, increasing risk for systemic metastases for those at high risk. On the other hand, the waiting time during pretreatment before surgery enables comprehensive systematic characterization of the primary tumor status before the decisions on adjuvant chemotherapy, opening a window to the use of precision in decision-making.

In this randomized controlled treatment trial, outcomes of novel precision methods to select right rectal cancer patients for treatment that they need will be compared to conventional treatment. The study aims to reduce over-treatment of those that most likely do not benefit from additional treatments. With the overall aim to reduce metastatic form of the disease, patients with high-risk features will be randomized to a treatment strategy with early systemic control by chemotherapy followed by circulating tumor DNA (ctDNA) and organoid-guided adjuvant therapy, or to conventional treatment strategy. Both state-of-the-art laboratory practice and routine diagnostic clinical pipelines are introduced to bring future diagnostic models of minimal residual disease and chemoresistance closer to current practice. The outcomes will reveal the clinical benefit of such strategy by recurrence-free survival at highest level of evidence, and produce important clinical outcome data on the application of ctDNA in everyday cancer treatment practice. The translational data on the use of ctDNA organoids to inform treatment decision and regimen selection will build knowledge of the use of such biomarkers as tools for clinical practice and clinical research. The results will be scalable worldwide in the practice of rectal cancer treatment.

Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer

Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer (SYNCOPE) - Approach on High-risk Group to Reduce Metastases

number of patients with detectable ctDNA at postoperative sample in the conventional treatment arm that are not assigned to chemotherapy

population distribution of PDO treatment response is compared to their corresponding clinical response by response MRI and pathological response and compared to organoid in vitro response

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Longitudinal Multimodal Response Assessment During Neoadjuvant Treatment of Rectal Cancer	NCT05524012	Locally Advance... Neoadjuvant Tre... Radiotherapy Adaptive Treatm...	Blood sample MRI scan	18 Years -	Jena University Hospital
Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer	NCT04842006	Colorectal Canc...	Total neoadjuva... Minimal residua... Long radiation ...	18 Years - 100 Years	Helsinki University Central Hospital
Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer	NCT04842006	Colorectal Canc...	Total neoadjuva... Minimal residua... Long radiation ...	18 Years - 100 Years	Helsinki University Central Hospital

Spots Global Cancer Trial Database for total neoadjuvant therapy (tnt)