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Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer (SYNCOPE)

Primary Purpose

Colorectal Cancer

Status
Recruiting
Phase
Not Applicable
Locations
Finland
Study Type
Interventional
Intervention
Total neoadjuvant therapy (TNT)
Minimal residual disease (MRD)
Long radiation therapy
Sponsored by
Helsinki University Central Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Helsinki University Central HospitalRecruiting
  • Tampere University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

TNT + precision

Conventional

Arm Description

Outcomes

Primary Outcome Measures

Recurrence-free survival
Recurrence-free survival
Postoperative ctDNA
number of patients with detectable ctDNA at postoperative sample in the conventional treatment arm that are not assigned to chemotherapy

Secondary Outcome Measures

CRC-specific survival
CRC-specific survival
overall survival
overall survival
number of surgically resected patients resected patients
R0-resection rate
local recurrence rate
complete pathological response response rate
complete clinical response rate
total uptake of chemotherapy
total uptake of chemotherapy
total uptake of chemotherapy
adverse effects of surgery effects of surgery
adverse effects of chemotherapy
adverse effects of chemotherapy
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

Full Information

First Posted
February 8, 2021
Last Updated
March 3, 2023
Sponsor
Helsinki University Central Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04842006
Brief Title
Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer
Acronym
SYNCOPE
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 20, 2021 (Actual)
Primary Completion Date
August 31, 2028 (Anticipated)
Study Completion Date
December 31, 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Helsinki University Central Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
93 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TNT + precision
Arm Type
Experimental
Arm Title
Conventional
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Total neoadjuvant therapy (TNT)
Intervention Description
Short radiotherapy (5X5 Gy) and capecitabine/oxaliplatin
Intervention Type
Diagnostic Test
Intervention Name(s)
Minimal residual disease (MRD)
Intervention Description
Postoperative MRD on circulating cell-free DNA
Intervention Type
Radiation
Intervention Name(s)
Long radiation therapy
Intervention Description
Long-course 50.4 Gy radiation with capecitabine
Primary Outcome Measure Information:
Title
Recurrence-free survival
Time Frame
3 years from surgery
Title
Recurrence-free survival
Time Frame
5 years from surgery
Title
Postoperative ctDNA
Description
number of patients with detectable ctDNA at postoperative sample in the conventional treatment arm that are not assigned to chemotherapy
Time Frame
3 weeks postoperatively
Secondary Outcome Measure Information:
Title
CRC-specific survival
Time Frame
3 years
Title
CRC-specific survival
Time Frame
5 years
Title
overall survival
Time Frame
3 years
Title
overall survival
Time Frame
5 years
Title
number of surgically resected patients resected patients
Time Frame
1 year
Title
R0-resection rate
Time Frame
1 year
Title
local recurrence rate
Time Frame
5 years postoperatively
Title
complete pathological response response rate
Time Frame
12 weeks after initiation of pretreatment
Title
complete clinical response rate
Time Frame
12 weeks after initiation of pretreatment
Title
total uptake of chemotherapy
Time Frame
1year
Title
total uptake of chemotherapy
Time Frame
3 years
Title
total uptake of chemotherapy
Time Frame
5 years
Title
adverse effects of surgery effects of surgery
Time Frame
1 year
Title
adverse effects of chemotherapy
Time Frame
1 year
Title
adverse effects of chemotherapy
Time Frame
3 years
Title
Treatment response by patient-derived organoid (PDO) therapy response
Description
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
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: rectal adenocarcinoma, 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: deficient mismatch repair (MMR) status, non-dihydropyrimidine dehydrogenase (DPYD) genotype, a contraindication to capecitabine, oxaliplatin or RT, or failing in blood tests that describe the adequate circulatory, liver and kidney function for chemotherapy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Toni T Seppala, MD, PhD
Phone
+358444722846
Email
toni.seppala@tuni.fi
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Toni T Seppala, MD, PhD
Organizational Affiliation
Tampere University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Helsinki University Central Hospital
City
Helsinki
State/Province
Uusimaa
ZIP/Postal Code
00029
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Toni T Seppala, MD, PhD
Phone
+358444722846
Email
toni.t.seppala@hus.fi
Facility Name
Tampere University Hospital
City
Tampere
ZIP/Postal Code
33520
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Toni Seppala, Prof
Phone
+358444722846
Email
toni.seppala@pirha.fi

12. IPD Sharing Statement

Plan to Share IPD
No

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Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer

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