Preoperative Short-Course Radiation Therapy With PROtons Compared to Photons In High-Risk RECTal Cancer (PRORECT) (PRORECT)
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|ClinicalTrials.gov Identifier: NCT04525989|
Recruitment Status : Recruiting
First Posted : August 25, 2020
Last Update Posted : May 7, 2021
|Condition or disease||Intervention/treatment||Phase|
|Rectal Cancer||Radiation: Radiation therapy||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||254 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Prospective randomized|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||April 20, 2021|
|Estimated Primary Completion Date :||March 2028|
|Estimated Study Completion Date :||March 2028|
Experimental: Proton therapy
5 x 5 Gy External radiation therapy with Protons
Radiation: Radiation therapy
5 x 5 Gy external radiation therapy
Active Comparator: Photon therapy
5 x 5 Gy External radiation therapy with Photons
Radiation: Radiation therapy
5 x 5 Gy external radiation therapy
- 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
- Incidence of grade >2 hematologic and non-hematologic toxicity [ Time Frame: Baseline up to five years after treatment ]
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.
- 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 ]Differences in patient reported outcomes (PRO) between treatment arms in the preoperative period, the postoperative period, and overall
- Proportion of patients being able to undergo full dose neoadjuvant chemotherapy [ Time Frame: From week 3 until week 20 of the trial ]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
- Tumour regression grading (mrTRG) [ Time Frame: Baseline to response evaluation week 16-17 of the trial ]Radiological assessment and comparison of tumour regression grading (mrTRG) between treatment arms
- Cost effectiveness analysis measured by QALY [ Time Frame: Time from randomization up to 5 years ]Health economic comparison between proton and photon treatment. Cost effectiveness analysis measured by QALY
- Disease free survival [ Time Frame: Time from randomization until first recurrence, local/regional/systemic or death ]Disease free survival after proton vs. photon treatment
- Overall survival [ Time Frame: Time from randomization until death ]Overall survival after proton vs. photon treatment
- Quality of Life (QLQ-C30) [ Time Frame: Baseline, 3 weeks, 3, 6, 9, 12, 24, 36 and 60 months ]Quality of life after proton vs. photon treatment (QLQ-C30)
- Difference in postoperative complications [ Time Frame: From week 17-20 of the trial up to 5 years ]Difference in postoperative complications between study arms measured by LARS score
- Clinical complete remission (cCR) [ Time Frame: From start of treatment up to 1 year ]Proportion of patients who reach a clinical complete remission (cCR), enter a watch-and-wait period and remain free of regrowth at least one year
- Incidence of acute lumbar plexus neuralgia [ Time Frame: From baseline until week 4 of the trial ]Difference between treatment arms in acute lumbar plexus neuralgia grade 1-3 measured as a change from baseline according to CTCAE 5.0
- Exploratory: Concentrations of CD8+ and FOXP3 + tumour-infiltrating T cells [ Time Frame: Postoperative pathology from week 17 until week 24 of the trial ]Difference between treatment arms in concentrations of CD8+ and FOXP3 + tumour-infiltrating T cells after given radiotherapy
- Exploratory: Difference in concentrations of CEA (carcinoembryonic antigen) between treatment arms [ Time Frame: CEA measurements at baseline, week 3, 6, 9 and 12 of the trial ]Change from baseline in concentrations of circulating CEA (carcinoembryonic antigen) between treatment arms
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04525989
|Contact: Alexander Valdman, MD, PhD||+46(0)email@example.com|
|Karolinska University Hospital, Theme Cancer, Dept of Pelvic cancer||Recruiting|
|Stockholm, Solna, Sweden, 17176|
|Contact: Tone Fokstuen, MD, PhD +46 724 69 48 26 firstname.lastname@example.org|
|Principal Investigator: Tone Fokstuen, MD, PhD|
|Principal Investigator:||Alexander Valdman, MD, PhD||Department of Radiotherapy, Karolinska University Hospital, Stockholm, Sweden|