Clinical trial NCT05524012: Longitudinal Multimodal Response Assessment During Neoadjuvant Treatment of Rectal Cancer
Official title: Planning Adaptive Treatment by Longitudinal Response Assessment Implementing MR Imaging, Liquid Biopsy and Analysis of Microenvironment During Neoadjuvant Treatment of Rectal Cancer (PRIMO)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Locally Advanced Rectal Carcinoma
Neoadjuvant Treatment
Radiotherapy
Adaptive Treatment
Keywords: total neoadjuvant therapy (TNT)
T2* MRI
circulating tumor cells
tumor infiltrating lymphocytes
liquid biopsy
DWI
rectal cancer
organ preservation
Lead sponsor: Jena University Hospital
Sponsor class: OTHER
First posted: 2022-09-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with locally advanced rectal cancer (LARC), receiving neoadjuvant chemoradiotherapy (CRT).

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Tumor regression grading (TRG)
timeFrame: after completion of neoadjuvant treatment (up to 10 months)
Secondary outcomes:
measure: MRI
timeFrame: up to 10 months, until resection
measure: Circulating Tumor Cells (CTC)
timeFrame: 5 years
measure: Tumor Infiltrating Lymphocytes (TIL)
timeFrame: up to 10 months, until resection
measure: PFS
timeFrame: 5 years
measure: OS
timeFrame: 5 years
measure: Surrogate marker: Interleukin 6 (IL-6)
timeFrame: 5 years
measure: Surrogate marker: Carcinoembryonic Antigen (CEA)
timeFrame: 5 years
Other outcomes:
Locations:
city: Jena
country: Germany
facility: Department of Radiotherapy and Radiation Oncology, Jena University Hospital
Study officials:
affiliation: Department for Radiotherapy and Radiooncology, Jena University Hospital
name: Andrea Wittig-Sauerwein, MD
role: PRINCIPAL_INVESTIGATOR
References: