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

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ClinicalTrials.gov Identifier: NCT03729687
Recruitment Status : Recruiting
First Posted : November 5, 2018
Last Update Posted : November 5, 2018
Sponsor:
Collaborator:
Swedish Cancer Society
Information provided by (Responsible Party):
Bengt Glimelius, Uppsala University

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

Condition or disease Intervention/treatment Phase
Rectal Cancer Combination Product: radiotherapy, capecitabine, oxaliplatin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Treatment with short-course radiotherapy (scRT) followed by 4 cycles of CAPOX chemotherapy and surgery in locally advanced rectal cancer while waiting for the results of the randomized phase III RAPIDO trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II of Short Course Radiation Therapy Followed by Pre-operative Chemotherapy and Surgery in Primary High-risk Rectal Cancer
Actual Study Start Date : July 4, 2016
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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
Combination Product: 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




Primary Outcome Measures :
  1. Pathological complete response (pCR) rate and clinical complete response (cCR) rate [ Time Frame: pCR assessed directly after surgery and cCR 12 months after end of treatment if no surgery is performed (cCR)] ]
    pCR assessed at pathological examination of the surgical specimen, cCR at clinical and radiological (MRI) examination


Secondary Outcome Measures :
  1. Disease-free survival [ Time Frame: 3 years ]
    non-radical surgery, recurrence or death within 3 years

  2. Neoadjuvant rectal score (NAR score) [ Time Frame: After surgery when the patological examination of the surgical specimen is completed ]
    Score from 0 - 100, where 0 is best

  3. Incidence of Treatment-Emergent Adverse Events [ Time Frame: within 60 days after end of treatment ]
    CTCAE v 4.0

  4. Long-term Adverse Events [ Time Frame: 4 years after end of treatment ]
    CTCAE v 4.0



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03729687


Contacts
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Contact: Bengt Glimelius, MD, PhD +46 70 6112432 bengt.glimelius@igp.uu.se

Locations
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Sweden
Akademiska sjukhuset Recruiting
Uppsala, Sweden, S-75185
Contact: Calin Radu, MD,PhD    +46 18 6110000    calin.radu@akademiska.se   
Sponsors and Collaborators
Uppsala University
Swedish Cancer Society
Investigators
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Principal Investigator: Bengt Glimelius, MD,PhD Uppsala University
  Study Documents (Full-Text)

Documents provided by Bengt Glimelius, Uppsala University:
Study Protocol  [PDF] June 14, 2018

Publications:
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Responsible Party: Bengt Glimelius, Senior Professor, consultant, Uppsala University
ClinicalTrials.gov Identifier: NCT03729687    
Other Study ID Numbers: LARCT-US v1.3
First Posted: November 5, 2018    Key Record Dates
Last Update Posted: November 5, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Bengt Glimelius, Uppsala University:
rectal cancer
high risk
total neoadjuvant treatment
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents