Comparing proton and photon radiation therapy for high-risk rectal cancer

Preoperative Short-Course Radiation Therapy With PROtons Compared to Photons In High-Risk RECTal Cancer (PRORECT): A Prospective Randomized Swedish Phase II Trial

This study is testing if proton beam radiation therapy can be better than traditional photon therapy for people with high-risk rectal cancer by seeing if it causes less stomach upset during treatment.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 254 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Karolinska University Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 9 sites (Stockholm, Solna and 8 other locations)
• Trial ID: NCT04525989 on ClinicalTrials.gov

What this trial studies

This study investigates the potential benefits of using proton beam radiation therapy compared to conventional photon beam radiation therapy in patients with locally advanced rectal cancer. The focus is on assessing whether proton therapy can reduce acute gastrointestinal toxicity, thereby improving patient tolerability to subsequent chemotherapy. Patients will receive a short course of radiation followed by chemotherapy and surgery, with the trial initially conducted at select centers and later expanded to others in the Skandion network. The study aims to provide insights into the effectiveness and safety of proton therapy in this patient population.

Who should consider this trial

Good fit: Ideal candidates are patients with newly diagnosed, biopsy-proven primary rectal adenocarcinoma that is locally advanced and meets specific high-risk criteria.

Not a fit: Patients with early-stage rectal cancer or those whose tumors do not meet the high-risk criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to reduced side effects from radiation therapy, enhancing the overall treatment experience for patients with rectal cancer.

How similar studies have performed: There are currently no published clinical reports or randomized trials comparing proton therapy to photon therapy specifically for locally advanced rectal cancer, making this approach novel.

Eligibility criteria

Inclusion Criteria:

Inclusion Criteria - Primary tumour characteristics

* 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

Inclusion Criteria - General

* 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

Where this trial is running

Stockholm, Solna and 8 other locations

• Karolinska University Hospital, Theme Cancer, Dept of Pelvic cancer — Stockholm, Solna, 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)

Study contacts

• Principal investigator: Alexander Valdman, MD, PhD — Department of Radiotherapy, Karolinska University Hospital, Stockholm, Sweden
• Study coordinator: Alexander Valdman, MD, PhD

Conditions Rectal Cancer; Proton therapy; Preoperative radiation; Short-course; Primary adenocarcinoma