Longitudinal Multimodal Response Assessment During Neoadjuvant Treatment of Rectal Cancer

Radiotherapy Clinical Trial

— PRIMO  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05524012
• Other study ID #: UKJ-PRIMO-2022
• Secondary ID: CSP-11LIFE Talen
• Status: Recruiting
• Start date: November 30, 2022
• Est. completion date: September 30, 2030

Study information

• Verified date: March 2023
• Source: Jena University Hospital
• Contact: Georg Wurschi, MD
• Phone: +49 3641 9 32 84 16
• Email: georg.wurschi[@]med.uni-jena.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 30, 2030
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Locally Advanced Rectal Carcinoma
• Neoadjuvant Treatment
• Radiotherapy
• Rectal Neoplasms

Intervention

Diagnostic Test:
• Blood sample
longitudinal blood samples for CTC monitoring

Device:
• MRI scan
longitudinal MRI scans (non-contrast enhanced)

Locations

Country	Name	City	State
Germany	Department of Radiotherapy and Radiation Oncology, Jena University Hospital	Jena

Sponsors (1)

Lead Sponsor	Collaborator
Jena University Hospital

Country where clinical trial is conducted

Germany, 

Outcome

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