Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer

NCT ID: NCT04842006

Last Updated: 2023-03-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-20
• Study Completion Date: 2031-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TNT + precision

Group Type: EXPERIMENTAL

Total neoadjuvant therapy (TNT)

Intervention Type: DRUG

Short radiotherapy (5X5 Gy) and capecitabine/oxaliplatin

Minimal residual disease (MRD)

Intervention Type: DIAGNOSTIC_TEST

Postoperative MRD on circulating cell-free DNA

Conventional

Group Type: ACTIVE_COMPARATOR

Long radiation therapy

Intervention Type: RADIATION

Long-course 50.4 Gy radiation with capecitabine

Interventions

Total neoadjuvant therapy (TNT)

Short radiotherapy (5X5 Gy) and capecitabine/oxaliplatin

Intervention Type: DRUG

Minimal residual disease (MRD)

Postoperative MRD on circulating cell-free DNA

Intervention Type: DIAGNOSTIC_TEST

Long radiation therapy

Long-course 50.4 Gy radiation with capecitabine

Intervention Type: RADIATION

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helsinki University Central Hospital

OTHER

Sponsor Role: lead

Responsible Party

Toni Seppala

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Toni T Seppala, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Tampere University Hospital

Locations

Helsinki University Central Hospital

Helsinki, Uusimaa, Finland

Site Status: RECRUITING

Tampere University Hospital

Tampere, , Finland

Site Status: RECRUITING

Countries

Finland

Central Contacts

Toni T Seppala, MD, PhD

Role: CONTACT

toni.seppala@tuni.fi

+358444722846

Facility Contacts

Toni T Seppala, MD, PhD

Role: primary

toni.t.seppala@hus.fi

+358444722846

Toni Seppala, Prof

Role: primary

toni.seppala@pirha.fi

+358444722846

Other Identifiers

HUS/155/2021

Identifier Type: -

Identifier Source: org_study_id