Chemoradiation and Consolidation Chemotherapy With or Without Oxaliplatin for Distal Rectal Cancer and Watch and Wait
CCHOWW
1 other identifier
interventional
216
3 countries
24
Brief Summary
Background: Neoadjuvant chemoradiation (nCRT) has been considered the preferred initial treatment strategy for distal rectal cancer. Advantages of this approach include improved local control after radical surgery but also the opportunity for organ preserving strategies (Watch and Wait - WW). Consolidation chemotherapy (cCT) regimens using fluoropyrimidine-based with or without oxaliplatin following nCRT have demonstrated to increase complete response and organ preservation rates among these patients. However, the benefit of adding oxaliplatin to cCt compared to fluoropyrimidine alone regimens in terms of primary tumor response remains unclear. Since oxaliplatin-treatment may be associated with considerable toxicity, it becomes imperative to understand the benefit of its incorporation into standard cCT regimens in terms of primary tumor response. The aim of the present trial is to compare the outcomes of 2 different cCT regimens following nCRT (fluoropyrimidine-alone versus fluoropyrimidine+oxaliplatin) for patients with distal rectal cancer. Methods: In this multi-centre study, patients with magnetic resonance-defined distal rectal tumors will be randomized on a 1:1 ratio to receive long-course chemoradiation (54Gy) followed by cCT with fluoropyrimidine alone versus fluoropyrimidine+oxaliplatin. Magnetic resonance (MR) will be analyzed centrally prior to patient inclusion and randomization. mrT2-3N0-1 tumor located no more than 1cm above the anorectal ring determined by sagittal views on MR will be eligible for the study. Tumor response will be assessed after 12 weeks from radiotherapy (RT) completion. Patients with clinical complete response (clinical, endoscopic and radiological) will be enrolled in an organ-preservation program (WW). The primary endpoint of this trial is decision to organ-preservation surveillance (WW) at 18 weeks from RT completion. Discussion: Long-course nCRT with cCT is associated with improved complete response rates and may be a very attractive alternative to increase the chances for organ-preservation strategies. Fluoropyrimidine-based cCT with or without oxaliplatin has never been investigated in the setting of a randomized trial to compare clinical response rates and the possibility of organ-preservation. The outcomes of this study may significantly impact clinical practice of patients with distal rectal cancer interested in organ-preservation.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Jul 2021
Longer than P75 for not_applicable
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 14, 2021
CompletedFirst Submitted
Initial submission to the registry
July 19, 2021
CompletedFirst Posted
Study publicly available on registry
August 11, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2027
November 27, 2024
November 1, 2024
5.7 years
July 19, 2021
November 25, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Decision to Watch and Wait due to clinical complete response
Decision to Watch and Wait due to clinical complete response achieved at 18 weeks from last date of radiation using clinical (DRE), endoscopic and radiological criteria (mrTRG grade) or near-complete clinical response (no progressive disease clinically, endoscopically or radiologically)
18 weeks from last date of radiation
Secondary Outcomes (5)
Surgery-free survival at 3 years
3 years from last date of radiation
Total Mesorectal Excision-free survival at 3 years
3 years from last date of radiation
Distant metastases free survival at 3 years
3 years from last date of radiation
Local regrowth-free survival at 3 years
3 years from last date of radiation
Colostomy-free survival at 3 years
3 years from last date of radiation
Study Arms (2)
Arm 1 - 5FU + Oxaliplatin
EXPERIMENTAL1\) RT (54Gy) plus daily concomitant capecitabine 825mg/m2 bid, followed by mFOLFOX6 or XELOX for 4 cycles (12 weeks), starting 1 week after radiotherapy ended;
Arm 2 - 5FU Only
ACTIVE COMPARATOR2\) RT (54Gy) plus daily concomitant capecitabine 825mg/m2 bid, followed by capecitabine 2000mg/m2/day for 14 days in a 21 days cycle for 4 cycles (12 weeks), starting 1 week after radiotherapy ended;
Interventions
Patients will receive 5FU + Oxaliplatin during the consolidation chemotherapy after long course chemoradiation
Patients will receive 5FU during the consolidation chemotherapy after long course chemoradiation
Eligibility Criteria
You may qualify if:
- Age ≥18 years;
- ECOG 0-2 or KPS≥70;
- Primary rectal adenocarcinoma (biopsy confirmed) within the reach of digital rectal examination (at least lower tip/border) by the attending colorectal surgeon;
- Endoscopic documentation;
- Abdominal and chest CT scans showing no evidence of metastatic disease;
- High-resolution magnetic resonance images performed at either 1.5T or 3.0T system using a phased array surface coil with: sagittal T2 images including the anal verge and the sacrum; axial oblique T2 weighted images acquired in a plane perpendicular to the long axis of the rectal wall guided by the sagittal images; coronal images acquired in parallel to the anal canal plane. Small field of view (16-18cm), 3mm section thickness, increased matrix size and increased number of signal averages are required;
- Radiological defining criteria (centralized):
- Lower edge of tumor at the level (max. 1cm distance) or below the anorectal ring defined at sagittal or coronal views;
- mrT2, mrT3 (any subclassification)
- mrN0-1 (≤3 radiologically positive lymph nodes)
- mrEMVI: any status
- mrMRF: any status
You may not qualify if:
- Pregnancy
- ECOG ≥3 or KPS\<70
- Unwilling to consent
- mrT4 or mrN2
- Previous pelvic irradiation
- Baseline neuropathy
- Receiving treatment of other anti-cancer drug or methods
- Presence of uncontrolled life threatening diseases
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (24)
Hospital Italiano de Buenos Aires
Buenos Aires, C1199CABA, Argentina
Hospital Ramos Mejia: Hospital General de Agudos Dr. Jose Maria Ramos Mejia
Buenos Aires, C1221ADC, Argentina
Hospital de Gastroenterologia Udaondo Ciudad de Buenos Aires
Buenos Aires, C1264AAACABA, Argentina
Hospital Britanico de Buenos Aires - Asociacion Civil
Buenos Aires, C1280AEB, Argentina
Hospital Curruca: Superintendencia de Bienestar Policia Federal Argentina
Buenos Aires, C1437JCP, Argentina
Hospital Alemão Oswaldo Cruz
São Paulo, São Paulo, 01327-001, Brazil
Hospital Felicio Rocho
Belo Horizonte, 30110-934, Brazil
Hospital das Clínicas da Faculdade de Medicina de Botucatu
Botucatu, 18607-741, Brazil
Complexo de Saude São João de Deus - Divinopolis
Divinópolis, 35500-227, Brazil
Hospital das Clinicas de Passo Fundo
Passo Fundo, 99010-260, Brazil
Irmandade Santa Casa de Misericordia de Porto Alegre
Porto Alegre, 90020-090, Brazil
Hospital das Clinicas de Porto Alegre
Porto Alegre, 90035-903, Brazil
União Brasileira de Educação e Assistencia - PUC-RS - Campus POA
Porto Alegre, 90160-092, Brazil
Hospital Militar de Area de Porto Alegre
Porto Alegre, 90440-191, Brazil
Centro Gaucho Integrado de Oncologia, hematologia, ensino e pesquisa
Porto Alegre, Brazil
Instituto Nacional do Cancer Jose Alencar Gomes da Silva - INCA
Rio de Janeiro, 20230-130, Brazil
Ensino e Terapia de Inovação Clínica AMO
Salvador, Brazil
Hospital Universitário de Santa Maria
Santa Maria, 97150-900, Brazil
Hospital Beneficencia Portuguesa
São Paulo, 01323-001, Brazil
Associação Beneficente Síria - Hospital do Coração
São Paulo, 04005-000, Brazil
Centro Paulista de Oncologia - CPO
São Paulo, 04538-132, Brazil
Hospital Primavera
São Paulo, 05059-060, Brazil
COT - Centro Oncológico do Triângulo S.A.
Uberlândia, Brazil
Médica Uruguaya Coorporación de Asistencia Médica
Montevideo, 11600, Uruguay
Related Publications (1)
Habr-Gama A, Sao Juliao GP, Ortega CD, Vailati BB, Araujo S, Jorge T, Sabbaga J, Rossi GL, D'Alpino R, Kater FR, Aguilar PB, Mattacheo A, Perez RO; Latin American Rectal Cancer Consortium (LARCC). A multi-centre randomized controlled trial investigating Consolidation Chemotherapy with and without oxaliplatin in distal rectal cancer and Watch & Wait. BMC Cancer. 2023 Jun 14;23(1):546. doi: 10.1186/s12885-023-10984-2.
PMID: 37316784DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rodrigo O Perez, Dr
Hospital Alemão Oswaldo Cruz
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- INVESTIGATOR
- Masking Details
- Patients and attending phisicians will not be blinded to the treatment arm randomized for each patient. However, as a strategy to reduce investigator's expectations and reduce inherent bias, the central committee will be blinded to the treatment arm. It is expected that blinding the central committee, who will be responsible for assessing the primary endpoint, any bias related to the investigator's expectation about the treatment arm and the chances of Watch and Wait will be nulled.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
July 19, 2021
First Posted
August 11, 2021
Study Start
July 14, 2021
Primary Completion (Estimated)
April 1, 2027
Study Completion (Estimated)
April 1, 2027
Last Updated
November 27, 2024
Record last verified: 2024-11