Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer

NCT04842006 | Recruiting

• 1 other identifier: HUS/155/2021
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 2

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.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• Recurrence-free survival

  3 years from surgery

• Recurrence-free survival

  5 years from surgery

• 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 Outcomes (16)

• CRC-specific survival

  3 years

• CRC-specific survival

  5 years

• overall survival

  3 years

• overall survival

  5 years

• number of surgically resected patients resected patients

  1 year

Study Arms (2)

TNT + precision

EXPERIMENTAL

Drug: Total neoadjuvant therapy (TNT); Diagnostic Test: Minimal residual disease (MRD)

Conventional

ACTIVE COMPARATOR

Radiation: Long radiation therapy

Interventions

Total neoadjuvant therapy (TNT) DRUG

Short radiotherapy (5X5 Gy) and capecitabine/oxaliplatin

TNT + precision

Minimal residual disease (MRD) DIAGNOSTIC_TEST

Postoperative MRD on circulating cell-free DNA

TNT + precision

Long radiation therapy RADIATION

Long-course 50.4 Gy radiation with capecitabine

Conventional

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Helsinki University Central Hospital: lead

Study Sites (2)

Helsinki University Central Hospital

Helsinki, Uusimaa, 00029, Finland

RECRUITING

Tampere University Hospital

Tampere, 33520, Finland

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Toni T Seppala, MD, PhD

  Tampere University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Toni T Seppala, MD, PhD

CONTACT

+358444722846; toni.seppala@tuni.fi

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: April 12, 2021
• Study Start: December 20, 2021
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): December 31, 2031
• Last Updated: March 6, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

FI (2)