Clinical trial NCT04842006: Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer
Official title: Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer (SYNCOPE) - Approach on High-risk Group to Reduce Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colorectal Cancer
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
First posted: 2021-04-12
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Recurrence-free survival
timeFrame: 3 years from surgery
measure: Recurrence-free survival
timeFrame: 5 years from surgery
measure: Postoperative ctDNA
timeFrame: 3 weeks postoperatively
Secondary outcomes:
measure: CRC-specific survival
timeFrame: 3 years
measure: CRC-specific survival
timeFrame: 5 years
measure: overall survival
timeFrame: 3 years
measure: overall survival
timeFrame: 5 years
measure: number of surgically resected patients resected patients
timeFrame: 1 year
measure: R0-resection rate
timeFrame: 1 year
measure: local recurrence rate
timeFrame: 5 years postoperatively
measure: complete pathological response response rate
timeFrame: 12 weeks after initiation of pretreatment
measure: complete clinical response rate
timeFrame: 12 weeks after initiation of pretreatment
measure: total uptake of chemotherapy
timeFrame: 1year
measure: total uptake of chemotherapy
timeFrame: 3 years
measure: total uptake of chemotherapy
timeFrame: 5 years
measure: adverse effects of surgery effects of surgery
timeFrame: 1 year
measure: adverse effects of chemotherapy
timeFrame: 1 year
measure: adverse effects of chemotherapy
timeFrame: 3 years
measure: Treatment response by patient-derived organoid (PDO) therapy response
timeFrame: 1 year
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
state: Uusimaa
city: Tampere
country: Finland
facility: Tampere University Hospital
Study officials:
affiliation: Tampere University Hospital
name: Toni T Seppala, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: