Clinical trial NCT05054959: Consolidation Versus Induction Chemotherapy in Total Neoadjuvant Therapy of Rectal Cancer With High Risk for Recurrence
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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Keywords: rectal cancer
total neoadjuvant therapy
induction chemotherapy
consolidation chemotherapy
Lead sponsor: Institute of Oncology Ljubljana
Sponsor class: OTHER
First posted: 2021-09-23
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: complete remission rate
timeFrame: 2 weeks after completiton of TNT
Secondary outcomes:
measure: Overall survival
timeFrame: after 3 years of follow-up
measure: Survival without recurrence of the disease
timeFrame: after 3 years of follow-up
measure: Disease free survival
timeFrame: after 3 years of follow-up
measure: local control
timeFrame: after 3 years of follow-up
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: Institute of Oncology
Study officials:
affiliation: Institute of Oncology Ljubljana
name: Vaneja Velenik, PD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.