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

NCT ID: NCT05054959

Last Updated: 2021-09-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-24

Study Completion Date

2027-12-31

Brief Summary

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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

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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.

Conditions

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Locally Advanced Rectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

consolidation chemotherapy

Intervention Type OTHER

6 cycles CAPOX after chemoradiotherapy

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.

Group Type ACTIVE_COMPARATOR

induction chemotherapy

Intervention Type OTHER

4 cycles CAPOX before and 2 cycles CAPOX after chemoradiotherapy

Interventions

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consolidation chemotherapy

6 cycles CAPOX after chemoradiotherapy

Intervention Type OTHER

induction chemotherapy

4 cycles CAPOX before and 2 cycles CAPOX after chemoradiotherapy

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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

* absolute contraindications for MR imaging
* distant metastases cannot be reliably excluded
* synchronous cancer
* chronic inflammatory bowel disease
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institute of Oncology Ljubljana

OTHER

Sponsor Role lead

Responsible Party

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Violeta Kaluza

Institute of Oncology Ljubljana

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Vaneja Velenik, PD

Role: PRINCIPAL_INVESTIGATOR

Institute of Oncology Ljubljana

Locations

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Institute of Oncology

Ljubljana, , Slovenia

Site Status RECRUITING

Countries

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Slovenia

Central Contacts

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Vaneja Velenik, PhD

Role: CONTACT

+386 15879297

Miha Orazem, MD

Role: CONTACT

+386 58792941

Facility Contacts

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Vaneja Velenik, PhD

Role: primary

+386 1 5879 297

Miha Orazem, MD

Role: backup

+386 1 5879 294

References

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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.

Reference Type BACKGROUND
PMID: 30210040 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27727065 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24717570 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33643528 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31652124 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31150315 (View on PubMed)

Other Identifiers

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KME 0120-214/2021/3

Identifier Type: -

Identifier Source: org_study_id

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