Rectal CancerPhase 2LARCT-USNCT03729687
Short Course Radiation Therapy Followed by Pre-operative Chemotherapy and Surgery in High-risk Rectal Cancer
A Phase 2 study testing radiotherapy, capecitabine, oxaliplatin in people with Rectal Cancer, run by Uppsala University at 1 site in Sweden.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- radiotherapy, capecitabine, oxaliplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 1 siteSweden
- Study dates
- 4 Jul 2016to 30 Jun 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • 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+).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II of Short Course Radiation Therapy Followed by Pre-operative Chemotherapy and Surgery in Primary High-risk Rectal Cancer
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
Read the 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
- Being tested
- radiotherapy, capecitabine, oxaliplatin
- Keywords
- rectal cancer, high risk, total neoadjuvant treatment
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
radiotherapy, capecitabine, oxaliplatinCombination 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
| Study group | Role | What they receive |
|---|---|---|
| LARCT-US | Experimental | 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 Receives: Combination Product: radiotherapy, capecitabine, oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response (pCR) rate and clinical complete response (cCR) rate
pCR assessed at pathological examination of the surgical specimen, cCR at clinical and radiological (MRI) examination
Measured: pCR assessed directly after surgery and cCR 12 months after end of treatment if no surgery is performed (cCR)]
Secondary outcomes (4)
Disease-free survival
non-radical surgery, recurrence or death within 3 years
Measured: 3 years
Neoadjuvant rectal score (NAR score)
Score from 0 - 100, where 0 is best
Measured: After surgery when the patological examination of the surgical specimen is completed
Incidence of Treatment-Emergent Adverse Events
CTCAE v 4.0
Measured: within 60 days after end of treatment
Long-term Adverse Events
CTCAE v 4.0
Measured: 4 years after end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2018
- Study start4 Jul 2016
- Primary completion30 May 2020
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by Uppsala UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 280 participants (actual)
Sponsor and investigators
- Lead sponsor
- Uppsala University
- Sponsor type
- University, hospital or other
- Collaborators
- Swedish Cancer Society
- Responsible party
- Principal investigator, Bengt Glimelius, Uppsala University
- Investigators
- Bengt Glimelius, MD,PhD, Principal investigator, Uppsala University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03729687
- Sponsor's protocol ID
- LARCT-US v1.3
- Acronym
- LARCT-US
- Status last verified
- Nov 2023
- First submitted
- 10 Oct 2018
- Last updated
- 30 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23742033Bujko 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.
PubMed 26884592Imam I, Khan T, Nilsson PJ, Glimelius B. Quality of life and late toxicity after total neoadjuvant treatment for locally advanced rectal cancer - LARCT-US. Radiother Oncol. 2026 Jan;214:111318. doi: 10.1016/j.radonc.2025.111318. Epub 2025 Nov 28.
PubMed 41319717
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II of Short Course Radiation Therapy Followed by Pre-operative Chemotherapy and Surgery in Primary High-risk Rectal Cancer
- ClinicalTrials.gov ID
- NCT03729687
- Acronym / sponsor ID
- LARCT-US / LARCT-US v1.3
- Conditions
- Rectal Cancer
- Keywords
- rectal cancer, high risk, total neoadjuvant treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 280 participants (actual)
- Lead sponsor
- Uppsala UniversityUniversity, hospital or other
- Collaborators
- Swedish Cancer Society
- Study start
- 4 Jul 2016 (actual)
- Primary completion
- 30 May 2020 (actual)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 5 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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
| Arm | Type | Receives |
|---|---|---|
| LARCT-US | Experimental | Combination Product: radiotherapy, capecitabine, oxaliplatinShort 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- • Histological proof of newly diagnosed primary adenocarcinoma of the rectum
Key exclusion criteria (12 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| radiotherapy, capecitabine, oxaliplatin5x5 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 | Combination product | LARCT-US |
Primary outcome
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
4 secondary outcomes
Disease-free survival
Time frame: 3 years
Neoadjuvant rectal score (NAR score)
Time frame: After surgery when the patological examination of the surgical specimen is completed
Incidence of Treatment-Emergent Adverse Events
Time frame: within 60 days after end of treatment
Long-term Adverse Events
Time frame: 4 years after end of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2023.
- Background: PubMed 23742033Nilsson 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.
- Background: PubMed 26884592Bujko 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.
- Derived from this study: PubMed 41319717Imam I, Khan T, Nilsson PJ, Glimelius B. Quality of life and late toxicity after total neoadjuvant treatment for locally advanced rectal cancer - LARCT-US. Radiother Oncol. 2026 Jan;214:111318. doi: 10.1016/j.radonc.2025.111318. Epub 2025 Nov 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bengt Glimelius, MD,PhD principal investigator
Uppsala University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing radiotherapy, capecitabine, oxaliplatin in people with Rectal Cancer, run by Uppsala University at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)]). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03729687, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2023.