Consolidation Versus Induction Chemotherapy in Total Neoadjuvant Therapy of Rectal Cancer With High Risk for Recurrence (ICONA)

July 8, 2026 updated by: Neža Gros, Institute of Oncology Ljubljana

Induction Versus Consolidation Chemotherapy in Total Neoadjuvant Therapy of Locally Advanced Rectal Cancer With High Risk of Recurrence (ICONA Study)

The purpose of this study is to identify the most promising treatment sequence in total neoadjuvant therapy for locally advanced rectal cancer with a high risk of recurrence.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

International recommendations for the treatment of locally advanced rectal cancer with a high risk of disease recurrence are inconsistent regarding the optimal sequence of total neoadjuvant therapy. In a German randomized study, a higher rate of pathological complete response was observed with consolidation chemotherapy.

This study compares induction chemotherapy followed by chemoradiotherapy and consolidation chemotherapy with chemoradiotherapy followed by consolidation chemotherapy in patients with locally advanced rectal cancer and high-risk features for recurrence.

Study Type

Interventional

Enrollment (Estimated)

62

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Slovenia
    • Slovenia
      • Ljubljana, Slovenia, Slovenia, 1000
        • Institute of Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:- histologically proven rectal adenocarcinoma

  • no distant metastases on CT scan (M0 disease)

  • at least one high risk factor for disease recurrence identified on magnetic resonance imaging (MRI):

    • T4 tumor (cT4)
    • N2 disease (cN2)
    • extramural venous invasion (cEMVI+)
    • positive lateral lymph nodes
    • distance of tumor to mesorectal fascia or positive lymph nodes is 1 mm or less (cMRF+)
  • capacity for informed consent
  • willingness to attend regular check-ups during and after treatment

Exclusion Criteria:history of previous irradiation in the pelvic area

  • absolute contraindications for MR imaging
  • distant metastases cannot be reliably excluded
  • synchronous cancer
  • chronic inflammatory bowel disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: consolidation chemotherapy

chemoradiation: intensity-modulated irradiation technique with simultaneous integrated boost to the tumor (IMRT-SIB) or with volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (VMAT-SIB) to the total tumor dose of 46.2 Gy in T1-3 tumors and 48.4 Gy in T4 tumors in 22 fractions with concomitant chemotherapy (CT) with capecitabine (dosage: 825 mg / m2 / 12 h per os continuously from the first to the last day of irradiation).

6 cycles of capecitabine and oxaliplatin (CAPOX) chemotherapy. One cycle of CAPOX CT lasts 3 weeks and consists of capecitabine 1000 mg / m2 / 12h per os for 1-14 days and oxaliplatin 130 mg / m2 intravenously in a two-hour infusion on day 1.
Drug: Consolidation CAPOX Chemotherapy
Six cycles of CAPOX chemotherapy are administered after chemoradiotherapy. CAPOX consists of capecitabine and oxaliplatin according to the study protocol.
Active Comparator: induction chemotherapy

4 cycles of induction CAPOX chemotherapy. One cycle of CAPOX CT lasts 3 weeks and consists of capecitabine 1000 mg / m2 / 12h per os for 1-14 days and oxaliplatin 130 mg / m2 intravenously in a two-hour infusion on day 1.

Chemoradiation: intensity-modulated irradiation technique with simultaneous integrated boost to the tumor (IMRT-SIB) or with volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (VMAT-SIB) to the total tumor dose of 46.2 Gy in T1-3 tumors and 48.4 Gy in T4 tumors in 22 fractions with concomitant CT with capecitabine (dosage: 825 mg / m2 / 12 h per os continuously from the first to the last day of irradiation).

2 cycles of consolidation CAPOX chemotherapy.
Drug: Induction CAPOX Chemotherapy
Four cycles of CAPOX chemotherapy are administered before chemoradiotherapy, followed by two cycles of CAPOX chemotherapy after chemoradiotherapy. CAPOX consists of capecitabine and oxaliplatin according to the study protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
complete remission rate
Time Frame: 2 weeks after completion of TNT
The proportion of complete responses will be defined as the sum of the proportions of pCR in operated patients and cCR in non-operated patients.
2 weeks after completion of TNT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: after 3 years of follow-up
time from randomization to death
after 3 years of follow-up
Disease free survival
Time Frame: after 3 years of follow-up
the time from the end of treatment (in the case of cCR) or surgery to the recurrence of disease, the onset of new cancer, death from cancer or other causes
after 3 years of follow-up
local control
Time Frame: after 3 years of follow-up
the time from the end of the treatment (in the case of cCR) or surgery to local recurrence
after 3 years of follow-up
Survival without recurrence of the disease
Time Frame: after 3 years of follow-up
time from the end of treatment (in case of cCR) or from radical surgery to death or recurrence of the disease - whichever comes first.
after 3 years of follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Oncology Ljubljana

Investigators

  • Principal Investigator: Vaneja Velenik, PD, Institute of Oncology Ljubljana

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 24, 2021

Primary Completion (Actual)

December 31, 2023

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

September 19, 2021

First Submitted That Met QC Criteria

September 19, 2021

First Posted (Actual)

September 23, 2021

Study Record Updates

Last Update Posted (Actual)

July 9, 2026

Last Update Submitted That Met QC Criteria

July 8, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KME 0120-214/2021/3

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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