Preoperative Short-Course Radiation Therapy With PROtons Compared to Photons In High-Risk RECTal Cancer (PRORECT)

NCT ID: NCT04525989

Last Updated: 2025-08-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 254 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-20
• Study Completion Date: 2028-03-31

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Proton therapy

5 x 5 Gy External radiation therapy with Protons

Group Type: EXPERIMENTAL

Radiation therapy

Intervention Type: RADIATION

5 x 5 Gy external radiation therapy

Photon therapy

5 x 5 Gy External radiation therapy with Photons

Group Type: ACTIVE_COMPARATOR

Radiation therapy

Intervention Type: RADIATION

5 x 5 Gy external radiation therapy

Interventions

Radiation therapy

5 x 5 Gy external radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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
• 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.

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.
• Patients with pacemaker or ICD
• Patients with bilateral hip protheses

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

Sponsors

Alexander Valdman

OTHER

Sponsor Role: lead

Responsible Party

Alexander Valdman

MD, PhD, Senior Consultant Radiation Oncologist

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Alexander Valdman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Radiotherapy, Karolinska University Hospital, Stockholm, Sweden

Locations

Karolinska University Hospital, Theme Cancer, Dept of Pelvic cancer

Stockholm, Solna, Sweden

Site Status: RECRUITING

Gävle Hospital

Gävle, , Sweden

Site Status: RECRUITING

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status: RECRUITING

Linköping University Hospital

Linköping, , Sweden

Site Status: RECRUITING

Skåne University Hospital

Lund, , Sweden

Site Status: RECRUITING

Stockholm South General Hospital

Stockholm, , Sweden

Site Status: RECRUITING

Sundsvall Hospital

Sundsvall, , Sweden

Site Status: RECRUITING

University Hospital of Umeå

Umeå, , Sweden

Site Status: RECRUITING

Uppsala University Hospital

Uppsala, , Sweden

Site Status: RECRUITING

Countries

Sweden

Central Contacts

Alexander Valdman, MD, PhD

Role: CONTACT

alexander.valdman@regionstockholm.se

+46(0)700021317

Facility Contacts

Tone Fokstuen, MD, PhD

Role: primary

tone.fokstuen@regionstockholm.se

+46 724 69 48 26

Marie Zajicova, MD

Role: primary

marie.zajicova@regiongavleborg.se

Mats Perman, MD

Role: primary

mats.perman@vgregion.se

Karolina Vernmark, MD

Role: primary

Karolina.Vernmark@regionostergotland.se

Marcus Johnsson, MD

Role: primary

Marcus.M.Johnsson@skane.se

Alice Rosén, MD

Role: primary

alice.rosen@regionstockholm.se

Petra Flygare, MD

Role: primary

petra.flygare@rvn.se

Berivan Mustafa, MD

Role: primary

Berivan.Mustafa@regionvasterbotten.se

Peter Nygren, MD

Role: primary

peter.nygren@igp.uu.se

References

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.

Reference Type: DERIVED

PMID: 36582423 (View on PubMed)

Other Identifiers

PRORECT

Identifier Type: -

Identifier Source: org_study_id