Locally Advanced Rectal CancerPhase 2ICONANCT05054959
Consolidation Versus Induction Chemotherapy in Total Neoadjuvant Therapy of Rectal Cancer With High Risk for Recurrence
A Phase 2 study testing Consolidation CAPOX Chemotherapy and Induction CAPOX Chemotherapy in people with Locally Advanced Rectal Cancer, run by Institute of Oncology Ljubljana at 1 site in Slovenia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Rectal Cancer
- What is being tested?
- Consolidation CAPOX Chemotherapy and Induction CAPOX Chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteSlovenia
- Study dates
- 24 Jun 2021to 31 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Locally Advanced Rectal Cancer
- Being tested
- Consolidation CAPOX Chemotherapy, Induction CAPOX Chemotherapy
- Keywords
- rectal cancer, total neoadjuvant therapy, induction chemotherapy, consolidation chemotherapy
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Consolidation CAPOX ChemotherapyDrug
Six cycles of CAPOX chemotherapy are administered after chemoradiotherapy. CAPOX consists of capecitabine and oxaliplatin according to the study protocol.
Induction CAPOX ChemotherapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| consolidation chemotherapy | Experimental | 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. Receives: Drug: Consolidation CAPOX Chemotherapy |
| induction chemotherapy | Active comparator | 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. Receives: Drug: Induction CAPOX Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
complete remission rate
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.
Measured: 2 weeks after completion of TNT
Secondary outcomes (4)
Overall survival
time from randomization to death
Measured: after 3 years of follow-up
Survival without recurrence of the disease
time from the end of treatment (in case of cCR) or from radical surgery to death or recurrence of the disease - whichever comes first.
Measured: after 3 years of follow-up
Disease free survival
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
Measured: after 3 years of follow-up
local control
the time from the end of the treatment (in the case of cCR) or surgery to local recurrence
Measured: after 3 years of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2021
- Study start24 Jun 2021
- Primary completion31 Dec 2023
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Rectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are randomized to one of two treatment sequences of total neoadjuvant therapy: induction chemotherapy followed by chemoradiotherapy and consolidation chemotherapy, or chemoradiotherapy followed by consolidation chemotherapy.
- Masking
- None (open label)
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute of Oncology Ljubljana
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Neža Gros, Institute of Oncology Ljubljana
- Investigators
- Vaneja Velenik, PD, Principal investigator, Institute of Oncology Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05054959
- Sponsor's protocol ID
- KME 0120-214/2021/3
- Acronym
- ICONA
- Status last verified
- Jul 2026
- First submitted
- 19 Sep 2021
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cercek A, Goodman KA, Hajj C, Weisberger E, Segal NH, Reidy-Lagunes DL, Stadler ZK, Wu AJ, Weiser MR, Paty PB, Guillem JG, Nash GM, Temple LK, Garcia-Aguilar J, Saltz LB. Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer. J Natl Compr Canc Netw. 2014 Apr;12(4):513-9. doi: 10.6004/jnccn.2014.0056.
PubMed 24717570Tuta M, Boc N, Brecelj E, Peternel M, Velenik V. Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure. World J Gastrointest Oncol. 2021 Feb 15;13(2):119-130. doi: 10.4251/wjgo.v13.i2.119.
PubMed 33643528Tuta M, Boc N, Brecelj E, Omejc M, Anderluh F, Ermenc AS, Peressutti AJ, Oblak I, Krebs B, Velenik V. Total neoadjuvant treatment of locally advanced rectal cancer with high risk factors in Slovenia. Radiol Oncol. 2019 Oct 25;53(4):465-472. doi: 10.2478/raon-2019-0046.
PubMed 31652124Fokas E, Allgauer M, Polat B, Klautke G, Grabenbauer GG, Fietkau R, Kuhnt T, Staib L, Brunner T, Grosu AL, Schmiegel W, Jacobasch L, Weitz J, Folprecht G, Schlenska-Lange A, Flentje M, Germer CT, Grutzmann R, Schwarzbach M, Paolucci V, Bechstein WO, Friede T, Ghadimi M, Hofheinz RD, Rodel C; German Rectal Cancer Study Group. Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO/ARO/AIO-12. J Clin Oncol. 2019 Dec 1;37(34):3212-3222. doi: 10.1200/JCO.19.00308. Epub 2019 May 31.
PubMed 31150315Golo D, But-Hadzic J, Anderluh F, Brecelj E, Edhemovic I, Jeromen A, Omejc M, Oblak I, Secerov-Ermenc A, Velenik V. Induction chemotherapy, chemoradiotherapy and consolidation chemotherapy in preoperative treatment of rectal cancer - long-term results of phase II OIGIT-01 Trial. Radiol Oncol. 2018 Sep 11;52(3):267-274. doi: 10.2478/raon-2018-0028.
PubMed 30210040But-Hadzic J, Anderluh F, Brecelj E, Edhemovic I, Secerov-Ermenc A, Hudej R, Jeromen A, Kozelj M, Krebs B, Oblak I, Omejc M, Vogrin A, Velenik V. Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial. Int J Radiat Oncol Biol Phys. 2016 Dec 1;96(5):1003-1010. doi: 10.1016/j.ijrobp.2016.08.031. Epub 2016 Aug 31.
PubMed 27727065
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Induction Versus Consolidation Chemotherapy in Total Neoadjuvant Therapy of Locally Advanced Rectal Cancer With High Risk of Recurrence (ICONA Study)
- ClinicalTrials.gov ID
- NCT05054959
- Acronym / sponsor ID
- ICONA / KME 0120-214/2021/3
- Conditions
- Locally Advanced Rectal Cancer
- Keywords
- rectal cancer, total neoadjuvant therapy, induction chemotherapy, consolidation chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Institute of Oncology LjubljanaUniversity, hospital or other
- Study start
- 24 Jun 2021 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 23 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants are randomized to one of two treatment sequences of total neoadjuvant therapy: induction chemotherapy followed by chemoradiotherapy and consolidation chemotherapy, or chemoradiotherapy followed by consolidation chemotherapy.
| Arm | Type | Receives |
|---|---|---|
| consolidation chemotherapy | Experimental | Drug: Consolidation CAPOX Chemotherapychemoradiation: 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. |
| induction chemotherapy | Active comparator | Drug: Induction CAPOX Chemotherapy4 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Consolidation CAPOX ChemotherapySix cycles of CAPOX chemotherapy are administered after chemoradiotherapy. CAPOX consists of capecitabine and oxaliplatin according to the study protocol. | Drug | consolidation chemotherapy |
| Induction CAPOX ChemotherapyFour 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. | Drug | induction chemotherapy |
Primary outcome
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.
4 secondary outcomes
Overall survival
Time frame: after 3 years of follow-up
Survival without recurrence of the disease
Time frame: after 3 years of follow-up
Disease free survival
Time frame: after 3 years of follow-up
local control
Time frame: after 3 years of follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2026.
- Background: PubMed 24717570Cercek A, Goodman KA, Hajj C, Weisberger E, Segal NH, Reidy-Lagunes DL, Stadler ZK, Wu AJ, Weiser MR, Paty PB, Guillem JG, Nash GM, Temple LK, Garcia-Aguilar J, Saltz LB. Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer. J Natl Compr Canc Netw. 2014 Apr;12(4):513-9. doi: 10.6004/jnccn.2014.0056.
- Background: PubMed 33643528Tuta M, Boc N, Brecelj E, Peternel M, Velenik V. Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure. World J Gastrointest Oncol. 2021 Feb 15;13(2):119-130. doi: 10.4251/wjgo.v13.i2.119.
- Background: PubMed 31652124Tuta M, Boc N, Brecelj E, Omejc M, Anderluh F, Ermenc AS, Peressutti AJ, Oblak I, Krebs B, Velenik V. Total neoadjuvant treatment of locally advanced rectal cancer with high risk factors in Slovenia. Radiol Oncol. 2019 Oct 25;53(4):465-472. doi: 10.2478/raon-2019-0046.
- Background: PubMed 31150315Fokas E, Allgauer M, Polat B, Klautke G, Grabenbauer GG, Fietkau R, Kuhnt T, Staib L, Brunner T, Grosu AL, Schmiegel W, Jacobasch L, Weitz J, Folprecht G, Schlenska-Lange A, Flentje M, Germer CT, Grutzmann R, Schwarzbach M, Paolucci V, Bechstein WO, Friede T, Ghadimi M, Hofheinz RD, Rodel C; German Rectal Cancer Study Group. Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO/ARO/AIO-12. J Clin Oncol. 2019 Dec 1;37(34):3212-3222. doi: 10.1200/JCO.19.00308. Epub 2019 May 31.
- Background: PubMed 30210040Golo D, But-Hadzic J, Anderluh F, Brecelj E, Edhemovic I, Jeromen A, Omejc M, Oblak I, Secerov-Ermenc A, Velenik V. Induction chemotherapy, chemoradiotherapy and consolidation chemotherapy in preoperative treatment of rectal cancer - long-term results of phase II OIGIT-01 Trial. Radiol Oncol. 2018 Sep 11;52(3):267-274. doi: 10.2478/raon-2018-0028.
- Background: PubMed 27727065But-Hadzic J, Anderluh F, Brecelj E, Edhemovic I, Secerov-Ermenc A, Hudej R, Jeromen A, Kozelj M, Krebs B, Oblak I, Omejc M, Vogrin A, Velenik V. Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial. Int J Radiat Oncol Biol Phys. 2016 Dec 1;96(5):1003-1010. doi: 10.1016/j.ijrobp.2016.08.031. Epub 2016 Aug 31.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vaneja Velenik, PD principal investigator
Institute of Oncology Ljubljana
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Consolidation CAPOX Chemotherapy and Induction CAPOX Chemotherapy in people with Locally Advanced Rectal Cancer, run by Institute of Oncology Ljubljana at 1 site in Slovenia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
complete remission rate (time frame: 2 weeks after completion of TNT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05054959, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2026.