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

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

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

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Rectal Cancer
• Intervention / Treatment: Other: consolidation chemotherapy; Other: induction chemotherapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 62
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Vaneja Velenik, PhD; Phone Number: +386 15879297; Email: vvelenik@onko-i.si
• Study Contact Backup: Name: Miha Orazem, MD; Phone Number: +386 58792941; Email: morazem@oko-i.si

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Recruiting
    • Institute of Oncology
    • Principal Investigator: Vaneja Velenik, PhD, MD
    • Contact: Vaneja Velenik, PhD; Phone Number: +386 1 5879 297; Email: vvelenik@onko-i.si
    • Contact: Miha Orazem, MD; Phone Number: +386 1 5879 294; Email: morazem@onko-i.si
    • Sub-Investigator: Ajra Secerov ErmencOblak, MD
    • Sub-Investigator: Janja Ocvirk, PhD, MD
    • Sub-Investigator: Miha Orazem, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

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 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.	Other: consolidation chemotherapy; 6 cycles CAPOX after chemoradiotherapy
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.	Other: induction chemotherapy; 4 cycles CAPOX before and 2 cycles CAPOX after chemoradiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 weeks after completiton of TNT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	time from randomization to death	after 3 years of follow-up
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.	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	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	after 3 years of follow-up

Collaborators and Investigators

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

Publications and helpful links

General 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2027

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): September 23, 2021
• Last Update Submitted That Met QC Criteria: September 19, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: rectal cancer; induction chemotherapy; consolidation chemotherapy; total neoadjuvant therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Recurrence; Rectal Neoplasms
• 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