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

NCT04525989 | Recruiting

• 1 other identifier: PRORECT
• Study Type: interventional
• Target: 254
• Locations: 1 country
• Sites: 9

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.

Conditions

Rectal Cancer

Keywords

Proton therapy; Preoperative radiation; Short-course; Primary adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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

  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

  Baseline up to five years after treatment

• Differences in patient reported outcomes (PRO)

  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

  From week 3 until week 20 of the trial

• Tumour regression grading (mrTRG)

  Baseline to response evaluation week 16-17 of the trial

• Cost effectiveness analysis measured by QALY

  Time from randomization up to 5 years

Other Outcomes (8)

• Disease free survival

  Time from randomization until first recurrence, local/regional/systemic or death

• Overall survival

  Time from randomization until death

• Quality of Life (QLQ-C30)

  Baseline, 3 weeks, 3, 6, 9, 12, 24, 36 and 60 months

Study Arms (2)

Proton therapy

EXPERIMENTAL

5 x 5 Gy External radiation therapy with Protons

Radiation: Radiation therapy

Photon therapy

ACTIVE COMPARATOR

5 x 5 Gy External radiation therapy with Photons

Radiation: Radiation therapy

Interventions

Radiation therapy RADIATION

5 x 5 Gy external radiation therapy

Photon therapy; Proton therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alexander Valdman: lead

Study Sites (9)

Karolinska University Hospital, Theme Cancer, Dept of Pelvic cancer

Stockholm, Solna, 17176, Sweden

RECRUITING

Gävle Hospital

Gävle, Sweden

RECRUITING

Sahlgrenska University Hospital

Gothenburg, Sweden

RECRUITING

Linköping University Hospital

Linköping, Sweden

RECRUITING

Skåne University Hospital

Lund, Sweden

RECRUITING

Stockholm South General Hospital

Stockholm, Sweden

RECRUITING

Sundsvall Hospital

Sundsvall, Sweden

RECRUITING

University Hospital of Umeå

Umeå, Sweden

RECRUITING

Uppsala University Hospital

Uppsala, Sweden

RECRUITING

Related Publications (1)

• 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.

  PMID: 36582423 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Alexander Valdman, MD, PhD

  Department of Radiotherapy, Karolinska University Hospital, Stockholm, Sweden

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander Valdman, MD, PhD

CONTACT

+46(0)700021317; alexander.valdman@regionstockholm.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, Senior Consultant Radiation Oncologist

Model Details: Prospective randomized

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: August 25, 2020
• Study Start: April 20, 2021
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (9)