Longitudinal Multimodal Response Assessment During Neoadjuvant Treatment of Rectal Cancer

Recruiting

• Conditions: Radiotherapy; Neoadjuvant Treatment; Locally Advanced Rectal Carcinoma; Adaptive Treatment

• Registration Number: NCT05524012
• Lead Sponsor: Jena University Hospital

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.

Study Timeline

• Study First Submitted: 2022-08-30
• Study First Submitted QC: 2022-08-30
• Study First Posted: 2022-09-01
• Study Start: 2022-11-30
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-13
• Last Update Posted: 2024-10-16
• Primary Completion: 2024-12-31
• Study Completion: 2030-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Department of Radiotherapy and Radiation Oncology, Jena University Hospital; 🇩🇪 Jena, Germany