Short Course Radiation Therapy Followed by Pre-operative Chemotherapy and Surgery in High-risk Rectal Cancer

NCT ID: NCT03729687

Last Updated: 2023-11-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-04
• Study Completion Date: 2025-06-30

Brief Summary

Patients with a primary rectal cancer without detectable distant metastasis who after locoregional therapy only, meaning preoperative radio(chemo)therapy plus surgery have at least a 40% risk of not having a CRM negative resection or a recurrence, local or distant, within three years will be treated with the short course 5 x 5 Gy radiation scheme followed by four cycles of combination chemotherapy (capecitabine and oxaliplatin) and TME surgery

Detailed Description

The multicentre, multinational RAPIDO (Rectal cancer And Pre-operative Induction therapy followed by Dedicated Operation, EudraCT number 2010-023957-12) closed patient entry in June 2016 after having randomised the planned number of 920 patients. In the study, patients were randomised to conventional chemoradiotherapy (CRT) to 50 Gy with capecitabine followed by surgery or to short-course radiotherapy (scRT, 5 x 5 Gy), 6 cycles of oxaliplatin-capecitabine (CAPOX) followed by surgery. In the CRT arm, adjuvant chemotherapy with 8 cycles of CAPOX was optional. At the time of closure of the RAPIDO study, it was discussed in Uppsala whether CRT should be the reference treatment for these high-risk rectal cancers, the experimental treatment or an alternative. Influenced by a Polish study reported by Bujko et al in 2016 with a similar design comparing CRT with scRT followed by 3 cycles of FOLFOX), it was decided that the reference treatment for patient with primary rectal cancer at high risk of failing either locally or systemically should be scRT followed by 4 cycles of CAPOX and surgery. This regimen, identical to the experimental arm in a Chinese trial (Stellar trial (ClinicalTrials.gov NCT02533271), preliminarily revealing promising pCR rates has since then been the reference treatment for patients having the same inclusion criteria as in the RAPIDO trial. Other centres in Sweden have also decided to use this regimen as reference treatment. A formal protocol is written and approved.

Conditions

Rectal Cancer

Keywords

rectal cancer; high risk; total neoadjuvant treatment

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LARCT-US

Short Course Radiation Therapy (5 x 5 Gy in 1 week, scRT) followed by 4 cycles of Pre-operative Chemotherapy using capecitabine and oxaliplatin (CAPOX) and Surgery in High-risk Rectal Cancer

Group Type: EXPERIMENTAL

radiotherapy, capecitabine, oxaliplatin

Intervention Type: COMBINATION_PRODUCT

5x5 Gy radiotherapy in 1 week, 4 cycles of CAPOX (capecitabine 1000 mg/m2 x2 d 1-14, oxaliplatin 130 mg/m2 d 1 every third week), surgery

Interventions

radiotherapy, capecitabine, oxaliplatin

5x5 Gy radiotherapy in 1 week, 4 cycles of CAPOX (capecitabine 1000 mg/m2 x2 d 1-14, oxaliplatin 130 mg/m2 d 1 every third week), surgery

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

• • Histological proof of newly diagnosed primary adenocarcinoma of the rectum

• Locally advanced tumour fulfilling at least one of the following criteria on pelvic MRI indicating high risk of failing locally and/or systemically (T4b, i.e. overgrowth to an adjacent organ or structure like the prostate, urinary bladder, uterus, sacrum, pelvic floor or side-wall (according to TNM version 7), cT4a, i.e. peritoneal involvement, extramural vascular invasion (EMVI+). N2, i.e. four or more lymph nodes in the mesorectum showing morphological signs on MRI indicating metastatic disease. Four or more nodes, whether enlarged or not, with a rounded, homogeneous appearance is thus not sufficient. Positive MRF, i.e. tumour or lymph node < 1 mm from the mesorectal fascia. Enlarged lateral nodes, > 1 cm (lat LN+).

Exclusion Criteria

• Extensive growth into cranial part of the sacrum (above S3) or the lumbosacral nerve roots indicating that surgery will never be possible even if substantial tumour down-sizing is seen.
• Presence of metastatic disease or recurrent rectal tumour. Familial Adenomatosis Polyposis coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn's disease or active ulcerative Colitis.
• Concomitant malignancies, except for adequately treated basocellular carcinoma of the skin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies must be disease-free for at least 5 years.
• Known DPD deficiency.
• Any contraindications to MRI (e.g. patients with pacemakers).
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
• Concurrent uncontrolled medical conditions.
• Any investigational treatment for rectal cancer within the past month.
• Pregnancy or breast feeding.
• Patients with known malabsorption syndromes or a lack of physical integrity of the upper gastrointestinal tract.
• Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac dysrhythmia, e.g. atrial fibrillation, even if controlled with medication) or myocardial infarction within the past 12 months.
• Patients with symptoms of peripheral neuropathy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swedish Cancer Society

OTHER

Sponsor Role: collaborator

Uppsala University

OTHER

Sponsor Role: lead

Responsible Party

Bengt Glimelius

Senior Professor, consultant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bengt Glimelius, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Uppsala University

Locations

Akademiska sjukhuset

Uppsala, , Sweden

Countries

Sweden

References

Nilsson PJ, van Etten B, Hospers GA, Pahlman L, van de Velde CJ, Beets-Tan RG, Blomqvist L, Beukema JC, Kapiteijn E, Marijnen CA, Nagtegaal ID, Wiggers T, Glimelius B. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer--the RAPIDO trial. BMC Cancer. 2013 Jun 7;13:279. doi: 10.1186/1471-2407-13-279.

Reference Type: BACKGROUND

PMID: 23742033 (View on PubMed)

Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Krynski J, Michalski W, Oledzki J, Kusnierz J, Zajac L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwolinski J, Winiarek M, Wisniowska K, Partycki M, Beczkowska K, Polkowski W, Stylinski R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Cisel B, Skorzewska M, Mielko J, Bebenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac L, Wojnar A, Lesniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kolodziejski L, Radkowski A, Zelazowska-Omiotek U, Czeremszynska B, Kepka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopylo R, Markiewicz W, Kedzierawski P, Wydmanski J; Polish Colorectal Study Group. Long-course oxaliplatin-based preoperative chemoradiation versus 5 x 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Ann Oncol. 2016 May;27(5):834-42. doi: 10.1093/annonc/mdw062. Epub 2016 Feb 15.

Reference Type: BACKGROUND

PMID: 26884592 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

LARCT-US v1.3

Identifier Type: -

Identifier Source: org_study_id