Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer

Not Applicable

Recruiting

• Conditions: Colorectal Cancer
• Interventions: Drug: Total neoadjuvant therapy (TNT); Radiation: Long radiation therapy; Diagnostic Test: Minimal residual disease (MRD)

• Registration Number: NCT04842006
• Lead Sponsor: Helsinki University Central Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-08
• Study First Submitted QC: 2021-04-09
• Study First Posted: 2021-04-12
• Study Start: 2021-12-20
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-03
• Last Update Posted: 2023-03-06
• Primary Completion: 2028-08-31
• Study Completion: 2031-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 93

Inclusion Criteria

1. rectal adenocarcinoma,
2. World Health Organization (WHO) performance status 0-1, assessed by the MDT to be able to undergo capecitabine and oxaliplatin (CAPOX) treatment, 3) extramural vein invasion by magnetic resonance imaging (mrEMVI+) and

4. assessed by the multi-disciplinary team (MDT) to require either radiotherapy (RT) or long chemoradiotherapy (CRT) by the current standards.

Exclusion Criteria

1. deficient mismatch repair (MMR) status,
2. non-dihydropyrimidine dehydrogenase (DPYD) genotype,
3. a contraindication to capecitabine, oxaliplatin or RT, or
4. failing in blood tests that describe the adequate circulatory, liver and kidney function for chemotherapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TNT + precision	Total neoadjuvant therapy (TNT)	-
TNT + precision	Minimal residual disease (MRD)	-
Conventional	Long radiation therapy	-

Primary Outcome Measures

Name	Time	Method
Recurrence-free survival	5 years from surgery
Postoperative ctDNA	3 weeks postoperatively	number of patients with detectable ctDNA at postoperative sample in the conventional treatment arm that are not assigned to chemotherapy

Secondary Outcome Measures

Name	Time	Method
R0-resection rate	1 year
adverse effects of chemotherapy	3 years
number of surgically resected patients resected patients	1 year
local recurrence rate	5 years postoperatively
complete clinical response rate	12 weeks after initiation of pretreatment
Treatment response by patient-derived organoid (PDO) therapy response	1 year	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
adverse effects of surgery effects of surgery	1 year
CRC-specific survival	5 years
complete pathological response response rate	12 weeks after initiation of pretreatment
total uptake of chemotherapy	5 years
overall survival	5 years

Trial Locations

Locations (2)

Tampere University Hospital; 🇫🇮 Tampere, Finland

Helsinki University Central Hospital; 🇫🇮 Helsinki, Uusimaa, Finland