ICONA: Consolidation Versus Induction Chemotherapy in Total Neoadjuvant Therapy of Rectal Cancer With High Risk for Recurrence
Study Details
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- complete remission rate [2 weeks after completiton 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.
Secondary Outcome Measures
- Overall survival [after 3 years of follow-up]
time from randomization to death
- Survival without recurrence of the disease [after 3 years of follow-up]
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 [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
- local control [after 3 years of follow-up]
the time from the end of the treatment (in the case of cCR) or surgery to local recurrence
Eligibility Criteria
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:
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T4 tumor (cT4)
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N2 disease (cN2)
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extramural venous invasion (cEMVI+)
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positive lateral lymph nodes
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distance of tumor to mesorectal fascia or positive lymph nodes is 1 mm or less (cMRF+)
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capacity for informed consent
-
willingness to attend regular check-ups during and after treatment
Exclusion Criteria:history of previous irradiation in the pelvic area
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absolute contraindications for MR imaging
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distant metastases cannot be reliably excluded
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synchronous cancer
-
chronic inflammatory bowel disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institute of Oncology | Ljubljana | Slovenia | 1000 |
Sponsors and Collaborators
- Institute of Oncology Ljubljana
Investigators
- Principal Investigator: Vaneja Velenik, PD, Institute of Oncology Ljubljana
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- Fokas E, Allgäuer 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, Grützmann R, Schwarzbach M, Paolucci V, Bechstein WO, Friede T, Ghadimi M, Hofheinz RD, Rödel 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.
- 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.
- 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.
- KME 0120-214/2021/3