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

Phase 2

Recruiting

• Conditions: Locally Advanced Rectal Cancer
• Interventions: Other: consolidation chemotherapy; Other: induction chemotherapy

• Registration Number: NCT05054959
• Lead Sponsor: Institute of Oncology Ljubljana

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.

Study Timeline

• Study Start: 2021-06-24
• Status Verified: 2021-09
• Study First Submitted: 2021-09-19
• Study First Submitted QC: 2021-09-19
• Last Update Submitted: 2021-09-19
• Study First Posted: 2021-09-23
• Last Update Posted: 2021-09-23
• Primary Completion: 2022-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 62

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
consolidation chemotherapy	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.
induction chemotherapy	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Overall survival	after 3 years of follow-up	time from randomization to death
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
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.

Trial Locations

Locations (1)

Institute of Oncology; 🇸🇮 Ljubljana, Slovenia