Rectal CancerPRORECTNCT04525989
Preoperative Short-Course Radiation Therapy With PROtons Compared to Photons In High-Risk RECTal Cancer (PRORECT)
A study testing Radiation therapy in people with Rectal Cancer, run by Alexander Valdman at 9 sites in Sweden.
Trial summary
To investigate a potential toxicity benefit of preoperative radiation therapy with protons compared to conventional photon beam radiation therapy in patients with locally advanced rectal cancer. 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?
- Radiation therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 254 participants
- Where
- 9 sitesSweden
- Study dates
- 20 Apr 2021to Mar 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Biopsy-proven, newly diagnosed primary rectal adenocarcinoma, i.e. with the lowest part of the tumour less than 16 cm from the anal verge detected using a rigid rectoscope.
- Locally advanced tumour fulfilling at least one of the following criteria on pelvic MRI indicating high risk of failing locally and/or systemically:
- Clinical stage (c) T4b, i.e. infiltration of an adjacent organ or structure like the prostate, urinary bladder, uterus, sacrum, pelvic floor or side-wall (according to TNM version 8).
- cT4a, i.e. peritoneal involvement.
- Extramural vascular invasion (EMVI+).
- N2-status regarded as metastatic according to ESGAR consensus criteria
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- Positive MRF, i.e. tumor or lymph node one mm or less from the mesorectal fascia.
- Metastatic lateral nodes (lat LN+) according to ESGAR consensus criteria
- Staging done within 6 weeks before start of radiotherapy. No contraindications to chemotherapy with CAPOX including adequate blood counts, (within 5 weeks prior to randomisation):
- white blood count ≥4.0 x 10*9/L
- platelet count ≥100 x 10*9/L
- clinically acceptable haemoglobin levels
- creatinine levels indicating renal clearance of ≥50 ml/min
- bilirubin ˂35 µmol/l.
- ECOG performance score ≤1
- Patient is considered to be mentally and physically fit for chemotherapy with CAPOX as judged by the oncologist.
- Age ≥18 years
- Written informed consent.
- Adequate potential for follow-up.
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.
- Patients with pacemaker or ICD
- Patients with bilateral hip protheses
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
Sweden9 sites, 9 recruiting
- Recruiting
Gävle Hospital
Gävle
Marie Zajicova, MD, marie.zajicova@regiongavleborg.se
Marie Zajicova, MD
- Recruiting
Sahlgrenska University Hospital
Gothenburg
Mats Perman, MD, mats.perman@vgregion.se
Mats Perman, MD
- Recruiting
Linköping University Hospital
Linköping
Karolina Vernmark, MD, Karolina.Vernmark@regionostergotland.se
Karolina Vernmark, MD
- Recruiting
Skåne University Hospital
Lund
Marcus Johnsson, MD, Marcus.M.Johnsson@skane.se
Marcus Johnsson, MD
- Recruiting
Karolinska University Hospital, Theme Cancer, Dept of Pelvic cancer
Stockholm, Solna, 17176
Tone Fokstuen, MD, PhD, +46 724 69 48 26, tone.fokstuen@regionstockholm.se
Tone Fokstuen, MD, PhD
- Recruiting
Stockholm South General Hospital
Stockholm
Alice Rosén, MD, alice.rosen@regionstockholm.se
Alice Rosén, MD
- Recruiting
Sundsvall Hospital
Sundsvall
Petra Flygare, MD, petra.flygare@rvn.se
Petra Flygare, MD
- Recruiting
University Hospital of Umeå
Umeå
Berivan Mustafa, MD, Berivan.Mustafa@regionvasterbotten.se
Berivan Mustafa, MD
- Recruiting
Uppsala University Hospital
Uppsala
Peter Nygren, MD, peter.nygren@igp.uu.se
Peter Nygren, MD
About this study
Official title: Preoperative Short-Course Radiation Therapy With PROtons Compared to Photons In High-Risk RECTal Cancer (PRORECT): A Prospective Randomized Swedish Phase II Trial
To investigate a potential toxicity benefit of preoperative radiation therapy with protons compared to conventional photon beam radiation therapy in patients with locally advanced rectal cancer.
Read the detailed description
The aim of this study is to investigate whether proton beam radiotherapy in locally advanced rectal cancer can offer meaningful reductions in acute gastrointestinal toxicity compared to standard treatment with photons which may improve patient's tolerability of neoadjuvant chemotherapy.
There are currently no published clinical reports evaluating the use of proton therapy in the upfront treatment of locally advanced rectal cancer. There are further no published randomized trials comparing radiotherapy with photon vs proton in locally advanced rectal cancer.
This is a prospective randomized trial, initially run at the limited number of centres but later expanded to other centres participating in the Skandion network. Patients will be treated with short course 5 x 5 Gy radiation scheme with either photons (standard arm) or protons (Skandion clinic) followed by four to six cycles of combination chemotherapy (capecitabine and oxaliplatin) and surgery. The rectal tumour will be removed by TME/PME surgery or more extensive surgery if required because of tumour extent.
All patients will receive at least 4 courses of CAPOX (Capecitabine b.i.d.1000 mg/m2 day 1-14 every 3 weeks, Oxaliplatin 130 mg/m2 day 1 every 3 weeks) week 3-14, followed by surgery at week 17-20.
- Conditions
- Rectal Cancer
- Being tested
- Radiation therapy
- Keywords
- Proton therapy, Preoperative radiation, Short-course, Primary adenocarcinoma
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiation therapyRadiation
5 x 5 Gy external radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Proton therapy | Experimental | 5 x 5 Gy External radiation therapy with Protons Receives: Radiation: Radiation therapy |
| Photon therapy | Active comparator | 5 x 5 Gy External radiation therapy with Photons Receives: Radiation: Radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of acute grade 2-5 gastrointestinal toxicity
The incidence of acute preoperative grade 2-5 gastrointestinal toxicity according to CTCAE v5.0 associated with proton vs. photon radiotherapy
Measured: From start of radiotherapy to planned start of the third (3) CAPOX cycle (week 9-10 of the trial)
Secondary outcomes (5)
Incidence of grade >2 hematologic and non-hematologic toxicity
The incidence of grade >2 hematologic (blood count, febrile neutropenia) and non-hematologic toxicity (general, genitourinary, gastrointestinal, skin) associated with protocol treatment, assessed by CTCAE v5.0 in the preoperative period, the postoperative period, and overall.
Patient reported side-effects will be assessed by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire, the QLQ-C30, version 3. The QLQ-C30 will be supplemented with the disease specific module (rectal-cancer) QLQ-CR29. During radiotherapy, daily reported symptoms will be investigated by a newly developed symptom scale, Radiotherapy related symptom assessment scale (RSAS). The questionnaire includes 13 items specific for current diagnose. The RSAS is a validated instrument for assessing symptom intensity and distress in patients with different cancer disease undergoing radiotherapy, with psychometric properties within the expected range.
Measured: Baseline up to five years after treatment
Differences in patient reported outcomes (PRO)
Differences in patient reported outcomes (PRO) between treatment arms in the preoperative period, the postoperative period, and overall
Measured: Baseline, Day 1-5, 2 and 3 weeks, 3, 6, 9, 12, 24, 36 and 60 months
Proportion of patients being able to undergo full dose neoadjuvant chemotherapy
Differences between treatment arms in proportion of patients being able to undergo full dose neoadjuvant chemotherapy i.e. at least 4 cycles of CAPOX or 6 cycles of FOLFOX
Measured: From week 3 until week 20 of the trial
Tumour regression grading (mrTRG)
Radiological assessment and comparison of tumour regression grading (mrTRG) between treatment arms
Measured: Baseline to response evaluation week 16-17 of the trial
Cost effectiveness analysis measured by QALY
Health economic comparison between proton and photon treatment. Cost effectiveness analysis measured by QALY
Measured: Time from randomization up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2020
- Study start20 Apr 2021
- Primary completionMar 2028 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective randomized
- Masking
- None (open label)
- Enrolment
- 254 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alexander Valdman
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Alexander Valdman, Karolinska University Hospital
- Investigators
- Alexander Valdman, MD, PhD, Principal investigator, Department of Radiotherapy, Karolinska University Hospital, Stockholm, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04525989
- Sponsor's protocol ID
- PRORECT
- Acronym
- PRORECT
- Status last verified
- Aug 2026
- First submitted
- 18 Aug 2020
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pedone C, Sorcini B, Staff C, Farlin J, Fokstuen T, Frodin JE, Nilsson PJ, Martling A, Valdman A. Preoperative short-course radiation therapy with PROtons compared to photons in high-risk RECTal cancer (PRORECT): Initial dosimetric experience. Clin Transl Radiat Oncol. 2022 Dec 17;39:100562. doi: 10.1016/j.ctro.2022.100562. eCollection 2023 Mar.
PubMed 36582423
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preoperative Short-Course Radiation Therapy With PROtons Compared to Photons In High-Risk RECTal Cancer (PRORECT): A Prospective Randomized Swedish Phase II Trial
- ClinicalTrials.gov ID
- NCT04525989
- Acronym / sponsor ID
- PRORECT / PRORECT
- Conditions
- Rectal Cancer
- Keywords
- Proton therapy, Preoperative radiation, Short-course, Primary adenocarcinoma
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 254 participants (estimated)
- Lead sponsor
- Alexander ValdmanUniversity, hospital or other
- Study start
- 20 Apr 2021 (actual)
- Primary completion
- Mar 2028 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 25 Aug 2020 (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.
To investigate a potential toxicity benefit of preoperative radiation therapy with protons compared to conventional photon beam radiation therapy in patients with locally advanced rectal cancer.
Detailed description
The aim of this study is to investigate whether proton beam radiotherapy in locally advanced rectal cancer can offer meaningful reductions in acute gastrointestinal toxicity compared to standard treatment with photons which may improve patient's tolerability of neoadjuvant chemotherapy.
There are currently no published clinical reports evaluating the use of proton therapy in the upfront treatment of locally advanced rectal cancer. There are further no published randomized trials comparing radiotherapy with photon vs proton in locally advanced rectal cancer.
This is a prospective randomized trial, initially run at the limited number of centres but later expanded to other centres participating in the Skandion network. Patients will be treated with short course 5 x 5 Gy radiation scheme with either photons (standard arm) or protons (Skandion clinic) followed by four to six cycles of combination chemotherapy (capecitabine and oxaliplatin) and surgery. The rectal tumour will be removed by TME/PME surgery or more extensive surgery if required because of tumour extent.
All patients will receive at least 4 courses of CAPOX (Capecitabine b.i.d.1000 mg/m2 day 1-14 every 3 weeks, Oxaliplatin 130 mg/m2 day 1 every 3 weeks) week 3-14, followed by surgery at week 17-20.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective randomized
| Arm | Type | Receives |
|---|---|---|
| Proton therapy | Experimental | Radiation: Radiation therapy5 x 5 Gy External radiation therapy with Protons |
| Photon therapy | Active comparator | Radiation: Radiation therapy5 x 5 Gy External radiation therapy with Photons |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Biopsy-proven, newly diagnosed primary rectal adenocarcinoma, i.e. with the lowest part of the tumour less than 16 cm from the anal verge detected using a rigid rectoscope.
- Locally advanced tumour fulfilling at least one of the following criteria on pelvic MRI indicating high risk of failing locally and/or systemically:
- Staging done within 6 weeks before start of radiotherapy. No contraindications to chemotherapy with CAPOX including adequate blood counts, (within 5 weeks prior to randomisation):
- ECOG performance score ≤1
- Patient is considered to be mentally and physically fit for chemotherapy with CAPOX as judged by the oncologist.
Key exclusion criteria (14 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 |
|---|---|---|
| Radiation therapy5 x 5 Gy external radiation therapy | Radiation | Photon therapy, Proton therapy |
Primary outcome
Incidence of acute grade 2-5 gastrointestinal toxicity
Time frame: From start of radiotherapy to planned start of the third (3) CAPOX cycle (week 9-10 of the trial)
The incidence of acute preoperative grade 2-5 gastrointestinal toxicity according to CTCAE v5.0 associated with proton vs. photon radiotherapy
5 secondary outcomes
Incidence of grade >2 hematologic and non-hematologic toxicity
Time frame: Baseline up to five years after treatment
Differences in patient reported outcomes (PRO)
Time frame: Baseline, Day 1-5, 2 and 3 weeks, 3, 6, 9, 12, 24, 36 and 60 months
Proportion of patients being able to undergo full dose neoadjuvant chemotherapy
Time frame: From week 3 until week 20 of the trial
Tumour regression grading (mrTRG)
Time frame: Baseline to response evaluation week 16-17 of the trial
Cost effectiveness analysis measured by QALY
Time frame: Time from randomization up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
- Derived from this study: PubMed 36582423Pedone C, Sorcini B, Staff C, Farlin J, Fokstuen T, Frodin JE, Nilsson PJ, Martling A, Valdman A. Preoperative short-course radiation therapy with PROtons compared to photons in high-risk RECTal cancer (PRORECT): Initial dosimetric experience. Clin Transl Radiat Oncol. 2022 Dec 17;39:100562. doi: 10.1016/j.ctro.2022.100562. eCollection 2023 Mar.
- 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.
Alexander Valdman, MD, PhD principal investigator
Department of Radiotherapy, Karolinska University Hospital, Stockholm, Sweden
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Radiation therapy in people with Rectal Cancer, run by Alexander Valdman at 9 sites 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 19 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alexander Valdman, MD, PhD (+46(0)700021317, alexander.valdman@regionstockholm.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of acute grade 2-5 gastrointestinal toxicity (time frame: From start of radiotherapy to planned start of the third (3) CAPOX cycle (week 9-10 of the trial)). 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 NCT04525989, which also lists 1 linked publication.
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 10 Aug 2026.