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

Primary Purpose

Locally Advanced Rectal Cancer

Status

Recruiting

Phase

Phase 2

Locations

Slovenia

Study Type

Interventional

Intervention

consolidation chemotherapy

induction chemotherapy

About this trial

This is an interventional treatment trial for Locally Advanced Rectal Cancer focused on measuring rectal cancer, total neoadjuvant therapy, induction chemotherapy, consolidation chemotherapy

Eligibility Criteria

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

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 MR imaging:
- 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

Sites / Locations

Institute of OncologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

consolidation chemotherapy

induction chemotherapy

Arm Description

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). 6 cycles of 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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall survival

time from randomization to death

Survival without recurrence of the disease

time from the end of treatment (in the case of cCR) or from radical surgery to death or recurrence of the disease - whichever comes first.

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

local control

the time from the end of the treatment (in the case of cCR) or surgery to local recurrence

Full Information

NCT ID

NCT05054959

First Posted

September 19, 2021

Last Updated

September 19, 2021

Sponsor

Institute of Oncology Ljubljana

1. Study Identification

Unique Protocol Identification Number

NCT05054959

Brief Title

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

Acronym

ICONA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Recruiting

Study Start Date

June 24, 2021 (Actual)

Primary Completion Date

December 31, 2022 (Anticipated)

Study Completion Date

December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Institute of Oncology Ljubljana

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of the study is to identify the most promising sequence of modalities in total neoadjuvant treatment of localy advanced rectal cancer with high risk of recurrence

Detailed Description

International recommendations for the treatment of LARC with a high risk of disease recurrence are inconsistent, regarding TNT. In Germain randomised study more pCR were achieved with consolidation chemotherapy. We will compare our standard approach (induction plus consolidation CT) with consolidation CT.

6. Conditions and Keywords

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

Locally Advanced Rectal Cancer

Keywords

rectal cancer, total neoadjuvant therapy, induction chemotherapy, consolidation chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Factorial Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

62 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

consolidation chemotherapy

Arm Type

Experimental

Arm Description

Arm Title

induction chemotherapy

Arm Type

Active Comparator

Arm Description

Intervention Type

Other

Intervention Name(s)

consolidation chemotherapy

Intervention Description

6 cycles CAPOX after chemoradiotherapy

Intervention Type

Other

Intervention Name(s)

induction chemotherapy

Intervention Description

4 cycles CAPOX before and 2 cycles CAPOX after chemoradiotherapy

Primary Outcome Measure Information:

Title

complete remission rate

Description

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.

Time Frame

2 weeks after completiton of TNT

Secondary Outcome Measure Information:

Title

Overall survival

Description

time from randomization to death

Time Frame

after 3 years of follow-up

Title

Survival without recurrence of the disease

Description

time from the end of treatment (in the case of cCR) or from radical surgery to death or recurrence of the disease - whichever comes first.

Time Frame

after 3 years of follow-up

Title

Disease free survival

Description

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

Time Frame

after 3 years of follow-up

Title

local control

Description

the time from the end of the treatment (in the case of cCR) or surgery to local recurrence

Time Frame

after 3 years of follow-up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 MR imaging: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Vaneja Velenik, PhD

Phone

+386 15879297

vvelenik@onko-i.si

First Name & Middle Initial & Last Name or Official Title & Degree

Miha Orazem, MD

Phone

+386 58792941

morazem@oko-i.si

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Vaneja Velenik, PD

Organizational Affiliation

Institute of Oncology Ljubljana

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institute of Oncology

City

Ljubljana

ZIP/Postal Code

1000

Country

Slovenia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Vaneja Velenik, PhD

Phone

+386 1 5879 297

vvelenik@onko-i.si

First Name & Middle Initial & Last Name & Degree

Miha Orazem, MD

Phone

+386 1 5879 294

morazem@onko-i.si

First Name & Middle Initial & Last Name & Degree

Vaneja Velenik, PhD, MD

First Name & Middle Initial & Last Name & Degree

Franc Anderluh, MD

First Name & Middle Initial & Last Name & Degree

Ajra Secerov ErmencOblak, MD

First Name & Middle Initial & Last Name & Degree

Janja Ocvirk, PhD, MD

First Name & Middle Initial & Last Name & Degree

Erik Brecelj, PhD, MD

First Name & Middle Initial & Last Name & Degree

Miha Orazem, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

24717570

Citation

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.

Results Reference

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PubMed Identifier

33643528

Citation

Tuta 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.

Results Reference

background

PubMed Identifier

31652124

Citation

Tuta 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.

Results Reference

background

PubMed Identifier

31150315

Citation

Fokas 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.

Results Reference

background

PubMed Identifier

30210040

Citation

Golo 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.

Results Reference

background

PubMed Identifier

27727065

Citation

But-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.

Results Reference

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

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