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

NCT05054959 | Active Not Recruiting Phase 2

• 1 other identifier: KME 0120-214/2021/3
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Locally Advanced Rectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 completion of TNT

Secondary Outcomes (4)

• Overall survival

  after 3 years of follow-up

• Survival without recurrence of the disease

  after 3 years of follow-up

• Disease free survival

  after 3 years of follow-up

• local control

  after 3 years of follow-up

Study Arms (2)

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.

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.

Drug: Induction CAPOX Chemotherapy

Interventions

Consolidation CAPOX Chemotherapy DRUG

Six cycles of CAPOX chemotherapy are administered after chemoradiotherapy. CAPOX consists of capecitabine and oxaliplatin according to the study protocol.

consolidation chemotherapy

Induction CAPOX Chemotherapy DRUG

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.

induction chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• absolute contraindications for MR imaging
• distant metastases cannot be reliably excluded
• synchronous cancer
• chronic inflammatory bowel disease

Sponsors & Collaborators

• Institute of Oncology Ljubljana: lead

Study Sites (1)

Institute of Oncology

Ljubljana, Slovenia, 1000, Slovenia

Location

Related Publications (6)

• 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.

  PMID: 24717570 BACKGROUND

• 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.

  PMID: 33643528 BACKGROUND

• 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.

  PMID: 31652124 BACKGROUND

• 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.

  PMID: 31150315 BACKGROUND

• 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.

  PMID: 30210040 BACKGROUND

• 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.

  PMID: 27727065 BACKGROUND

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Vaneja Velenik, PD

  Institute of Oncology Ljubljana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: September 19, 2021
• First Posted: September 23, 2021
• Study Start: June 24, 2021
• Primary Completion: December 31, 2023
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 9, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)