Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer

Colorectal Cancer Clinical Trial

— SYNCOPE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04842006
• Other study ID #: HUS/155/2021
• Status: Recruiting
• Phase: N/A
• Start date: December 20, 2021
• Est. completion date: December 31, 2031

Study information

• Verified date: March 2023
• Source: Helsinki University Central Hospital
• Contact: Toni T Seppala, MD, PhD
• Phone: +358444722846
• Email: toni.seppala[@]tuni.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 93
• Est. completion date: December 31, 2031
• Est. primary completion date: August 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• Total neoadjuvant therapy (TNT)
Short radiotherapy (5X5 Gy) and capecitabine/oxaliplatin

Diagnostic Test:
• Minimal residual disease (MRD)
Postoperative MRD on circulating cell-free DNA

Radiation:
• Long radiation therapy
Long-course 50.4 Gy radiation with capecitabine

Locations

Country	Name	City	State
Finland	Helsinki University Central Hospital	Helsinki	Uusimaa
Finland	Tampere University Hospital	Tampere

Sponsors (1)

Lead Sponsor	Collaborator
Helsinki University Central Hospital

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence-free survival		3 years from surgery
Primary	Recurrence-free survival		5 years from surgery
Primary	Postoperative ctDNA	number of patients with detectable ctDNA at postoperative sample in the conventional treatment arm that are not assigned to chemotherapy	3 weeks postoperatively
Secondary	CRC-specific survival		3 years
Secondary	CRC-specific survival		5 years
Secondary	overall survival		3 years
Secondary	overall survival		5 years
Secondary	number of surgically resected patients resected patients		1 year
Secondary	R0-resection rate		1 year
Secondary	local recurrence rate		5 years postoperatively
Secondary	complete pathological response response rate		12 weeks after initiation of pretreatment
Secondary	complete clinical response rate		12 weeks after initiation of pretreatment
Secondary	total uptake of chemotherapy		1year
Secondary	total uptake of chemotherapy		3 years
Secondary	total uptake of chemotherapy		5 years
Secondary	adverse effects of surgery effects of surgery		1 year
Secondary	adverse effects of chemotherapy		1 year
Secondary	adverse effects of chemotherapy		3 years
Secondary	Treatment response by patient-derived organoid (PDO) therapy response	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	1 year