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RandomizEd controlled trial for pre-operAtive dose-escaLation BOOST in locally advanced rectal cancer (RECTAL BOOST study): study protocol for a randomized controlled trial.

ABSTRACT: BACKGROUND:Treatment for locally advanced rectal cancer (LARC) consists of chemoradiation therapy (CRT) and surgery. Approximately 15% of patients show a pathological complete response (pCR). Increased pCR-rates can be achieved through dose escalation, thereby increasing the number patients eligible for organ-preservation to improve quality of life (QoL). A randomized comparison of 65 versus 50Gy with external-beam radiation alone has not yet been performed. This trial investigates pCR rate, clinical response, toxicity, QoL and (disease-free) survival in LARC patients treated with 65Gy (boost + chemoradiation) compared with 50Gy standard chemoradiation (sCRT). METHODS/DESIGN:This study follows the 'cohort multiple randomized controlled trial' (cmRCT) design: rectal cancer patients are included in a prospective cohort that registers clinical baseline, follow-up, survival and QoL data. At enrollment, patients are asked consent to offer them experimental interventions in the future. Eligible patients-histologically confirmed LARC (T3NxM0 <1 mm from mesorectal fascia, T4NxM0 or TxN2M0) located ?10 cm from the anorectal transition who provided consent for experimental intervention offers-form a subcohort (n = 120). From this subcohort, a random sample is offered the boost prior to sCRT (n = 60), which they may accept or refuse. Informed consent is signed only after acceptance of the boost. Non-selected patients in the subcohort (n = 60) undergo sCRT alone and are not notified that they participate in the control arm until the trial is completed. sCRT consists of 50Gy (25 × 2Gy) with concomitant capecitabine. The boost (without chemotherapy) is given prior to sCRT and consists of 15 Gy (5 × 3Gy) delivered to the gross tumor volume (GTV). The primary endpoint is pCR (TRG 1). Secondary endpoints include acute grade 3-4 toxicity, good pathologic response (TRG 1-2), clinical response, surgical complications, QoL and (disease-free) survival. Data is analyzed by intention to treat. DISCUSSION:The boost is delivered prior to sCRT so that GTV adjustment for tumor shrinkage during sCRT is not necessary. Small margins also aim to limit irradiation of healthy tissue. The cmRCT design provides opportunity to overcome common shortcomings of classic RCTs, such as slow recruitment, disappointment-bias in control arm patients and poor generalizability. TRIAL REGISTRATION:The Netherlands Trials Register NL46051.041.13. Registered 22 August 2013. ClinicalTrials.gov NCT01951521 . Registered 18 September 2013.

SUBMITTER: Burbach JP

PROVIDER: S-EPMC4344756 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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RandomizEd controlled trial for pre-operAtive dose-escaLation BOOST in locally advanced rectal cancer (RECTAL BOOST study): study protocol for a randomized controlled trial.

Burbach J P Maarten JP Verkooijen Helena M HM Intven Martijn M Kleijnen Jean-Paul J E JP Bosman Mirjam E ME Raaymakers Bas W BW van Grevenstein Wilhelmina M U WM Koopman Miriam M Seravalli Enrica E van Asselen Bram B Reerink Onne O

Trials 20150222

<h4>Background</h4>Treatment for locally advanced rectal cancer (LARC) consists of chemoradiation therapy (CRT) and surgery. Approximately 15% of patients show a pathological complete response (pCR). Increased pCR-rates can be achieved through dose escalation, thereby increasing the number patients eligible for organ-preservation to improve quality of life (QoL). A randomized comparison of 65 versus 50Gy with external-beam radiation alone has not yet been performed. This trial investigates pCR r ...[more]

PMID: 25888548

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Project description:ObjectiveThe study was prospectively designed as a single-arm, single-institution prospective trial of pre-operative concomitant hyperfractionated radiotherapy (HART) with co-administration of chemotherapy based on 5-fluorouracil (5FU) in patients with T2/N+ or T3/any N resectable mid-low primary rectal cancer. The aim of the study was to assess the safety and efficacy of accelerated HART with concurrent 5FU-based chemotherapy in patients with locally advanced rectal cancer.MethodsPatients with resectable locally advanced (≥T3 or N+) rectal cancer were eligible. The patients received total dose 42 Gy in 28 fractions of 1.5 Gy, two times daily, with at least 8 h of interval, with concurrent chemotherapy: 325 mg m-2 of 5FU (bolus) on Days 1-3 and Days 16-18 (except for cN0 patients for whom only one cycle on Days 1-3 was prescribed). The primary end point included tolerance, post-operative complication rate and pathological response rate. The secondary end points included locoregional relapse-free survival, metastasis-free survival and overall survival.ResultsOut of 53 enrolled patients; 2 did not undergo surgery. Of the 51 patients evaluable for pathological response, there were 8 (15.6%), 20 (39.3%), 18 (35.3%) and 5 (9.8%) patients with tumour regression grade 0, 1, 2 and 3, respectively. Downstaging of the primary tumour and lymph nodes was observed in 22 (43%) and 25 (49%) patients, respectively. The primary tumour ypCR (ypT0) rate was 15% (8/51). The nodal ypCR rate for cN+ patients was 60% (21/35). The total ypCR (ypT0N0M0) rate was 11% (6/51). Toxicity included: Grade 3 diarrhoea (4/51, 7.8%), Grade 2 diarrhoea (22/51, 43.1%), Grade 2 leukopenia (7/51, 13.7%), Grade 2 neutropenia (6/51, 11.7%) and Grade 1 thrombocytopenia (3/51, 5.9%). No Grade 4 toxicity was reported. Nine patients (18%) presented with post-operative complications (during the 3 months after surgery). There were 6 locoregional relapses (11.8%) and distant metastasis occurred in 11 patients (21.6%). The 2-year cumulative locoregional relapse-free survival, metastasis-free survival and overall survival was 87%, 79% and 89%, respectively.ConclusionThe proposed pre-operative HART with co-administration of 5FU had acceptable toxicity profile and provided satisfactory rate of ypCR. This created rationale to initiate a Phase III randomized study that was registered under ClinicalTrials.gov Identifier: NCT01814969. Advances in knowledge: The results of this research show that responders to pre-operative radiochemotherapy have favourable outcome. Tumour regression grade as prognostic clinical feature holds the promise of better classifying patients at high risk of local and systemic recurrence and this issue may be an interesting objective for future research.

Project description:PurposeThe standard of care in locally advanced rectal cancer is preoperative treatment with fluoropyrimidine-based chemoradiotherapy. Sorafenib works synergistically with radiation and inhibits Ras/Raf, PDFGR, and VEGFR. This phase I study evaluated the safety and efficacy of sorafenib with infusional 5-fluorouracil (5-FU) and radiation in patients with locally advanced rectal cancer.Methods and materialsPatients with confirmed stage II or III rectal cancer were recruited in 4 cohorts of 3 patients per dose level, with an expansion cohort at the maximum tolerated dose. A 3+3 dose escalation design was used. Radiation was given in 28 fractions at 1.8 Gy (50.4 Gy) day 1-5 at all dose levels. Initial dose of sorafenib was 200mg qd and titrated up to 400mg BID to determine the MTD. Standard dose of infusional 5-FU was used (225 mg/m(2)/24h). Patients underwent surgery 6-10 weeks after neoadjuvant therapy.ResultsBetween August 2011 and August 2014, 17 patients (median age of 54 years) were enrolled. After toxicities requiring dose interruptions were observed in cohort 1 (2 patients with grade 2 (G2) and grade 3 (G3) hand foot skin reaction and 1 patient with G2 mucositis), the protocol was amended, changing administration of chemotherapy and sorafenib from daily to days 1-5 only. With the amended protocol, the primary G3 toxicity was hypertension in 2 patients at the 200-mg adjusted dose level (day1-5) and 1 patient at the 400-mg twice daily dose level. One patient had G3 ALT elevation at 400mg, and no grade IV toxicities were observed. G1 and G2 toxicities included hand-foot skin reaction, diarrhea, mucositis, nausea, fatigue, and proctitis. No perioperative complications were seen. Two patients refused to undergo surgery. The pathological complete remission (pCR) rate was 33%, and downstaging was observed in 85.7% of patients. Median neoadjuvant rectal cancer score was 8.7.ConclusionsWith the changed dosing schedule, this regimen was very well tolerated. The tumor pCR and downstaging rates are encouraging and support further clinical investigation of this regimen.

Project description:BACKGROUND: The number of people with diabetes is increasing worldwide, especially in developing South Asian countries. Therefore, preventing diabetes at the early stages has become an important issue. Recent clinical trials, systematic reviews, and meta-analysis have shown that zinc has beneficial effects on glycemic and metabolic control in those with diabetes. The present study is designed to evaluate the effects of zinc supplementation on glycemic control and other metabolic parameters in those with pre-diabetes. METHODS/DESIGN: The study will be conducted as a randomized, double-blind, placebo-controlled clinical trial for a period of 12 months at the Faculty of Medicine, University of Colombo, Sri Lanka. The study has been approved by the Ethics Review Committee of Faculty of Medicine, University of Colombo (EC/11/189). A total of 200 adults (age 18-60 years) with pre-diabetes will be recruited for the study. They will be stratified according to age, gender, and body mass index and randomly assigned into the test and placebo groups on a 1:1 ratio. The zinc capsules, each weighing 456 mg, will contain the following ingredients:zinc sulfate monohydrate 55.096 mg (elemental zinc 20 mg), lactose monohydrate 399.504 mg, and stearic acid 1.400 mg. The placebo capsule with the same weight will be comprised of lactose monohydrate 454.600 mg and stearic acid 1.400 mg. The subjects will receive either zinc 20 mg capsules or placebo daily for a period of 12 months. The study drugs will be double blinded to both investigators and subjects. The visits and the evaluations will be done as follows: screening (visit 0), 1 month (visit 1), 3 month (visit 2), 6 month (visit 3), and 12 month (visit 4). The following primary outcome measures will be evaluated:fasting plasma glucose (FPG), post oral glucose tolerance test (OGTT), serum insulin, HbA1c, total/low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol, triglycerides, serum zinc, and appetite using a visual analog scale. Secondary outcome measures include: blood pressure, anthropometry, and dietary assessment using a validated food frequency questionnaire. Data will be analyzed using SPSS v16. DISCUSSION: The present protocol will aim to establish the beneficial effects of zinc supplementation on disease progression in those with pre-diabetes and also establish its effectiveness in the prevention of diabetes mellitus. TRIAL REGISTRATION: Sri Lanka Clinical Trial Registry: SLCTR/2012/010.

Project description:BackgroundFemur fracture is a major burden among elderly people, leading patients to be bedridden for a long time in the hospital. The body is more likely to be in a catabolic state as a result of the prolonged fasting period required for surgery, leading to an increase in insulin resistance. Pre-operative carbohydrate loading has been shown to improve postoperative outcomes in several countries. The study aimed to evaluate the effect of pre-operative carbohydrate loading in femur fracture surgery.MethodsThis study was single-center, hospital-based, open-label, parallel-group randomized controlled trial conducted between August 2020 and November 2021. A total of 66 participants, aged 50 years and above having femur fractures planned for surgery were included in this study and assigned to the control (n = 33) and study (n = 33) groups through computer-generated random numbers. The control group was kept fasting from midnight to the next morning as in existence while the study group was intervened with carbohydrate loading according to the Enhanced Recovery After Surgery (ERAS) protocol. The pre-operative nutritional status was identified and the postoperative outcomes were measured using the Visual Analogue Score (VAS), Cumulative Ambulatory Score (CAS), and Modified Barthel Index (MBI) scoring systems. Statistical analyses were performed using the Chi-square test and the Student's two-sample t-test to compare the outcomes between the two groups.ResultsAll the participants completed the study. There was a significant reduction in the average postoperative pain in the carbohydrate loading group (VAS: 4.8 (SD ± 1.8), 95% CI: 4.7-5.4) as compared to the control group (VAS: 6.1 (SD ± 2.1), 95% CI: 5.3-6.8). The average CAS showed a significant improvement in regaining the mobility function of participants in the study group (CAS: 8.1 (SD ± 2.8), 95% CI: 7.1-9.1) than that of the control group (CAS: 6.8 (SD ± 2.8), 95% CI: 5.8-7.8). The mean MBI score of the participants at the time of discharge from the hospital was higher in the study group (MBI:13.1 (SD ± 2.3), 95% CI: 12.2-13.9) compared to the control group (MBI: 11.8 (SD ± 3.1), 95% CI:10.6-12.9). Similarly, the length of hospital stay after surgery had decreased in the study group than in the control group.ConclusionsThe uptake of carbohydrate loading showed reduced post-operative pain, enhanced functional mobility, and decreased length of hospital stay. This study warrants larger trials to show the effect of pre-operative carbohydrate loading in a clinical setting.Trial registrationNCT04838366, first registered on 09/042021 ( https://clinicaltrials.gov/ct2/show/NCT04838366 ).

Project description:Objective: Audio-visual interventions have been used to provide relevant patient information to reduce pre-operative anxiety in children. The aim of the study was to investigate whether self-reported state anxiety in children could be reduced by presenting a child-friendly educational video on the day of surgery. Methods: A prospective, single-blinded, two-armed, randomized controlled study was designed with three measurement time points including 90 children (6-17 years) and their parents. In the intervention group (IG), the children and their parents were shown a child-friendly video explaining the perioperative procedures that would be applied during the hospital stay, in addition to receiving standard information. In the control group (CG), children and parents received standard information provided by the nursing staff. The primary outcome was any change in the children's pre-operative state anxiety levels, as measured by the State-Trait Operation Anxiety Inventory (STOA). A secondary outcome was patient satisfaction regarding the received information. Results: Anxiety was significantly reduced in both groups after receiving either the intervention plus standard information or the standard information only. No significant difference in anxiety reduction was observed between the IG and the CG. However, the children and parents in the IG reported fewer worries than those in the CG. Conclusion: A child-friendly, educational video can be an additional tool for providing patient information and reducing pre-operative anxiety in children and their parents. Further studies should focus on the timing of the intervention and on age- and developmentally appropriate information formats and contents to address children's pre-operative anxiety. Clinical Trial Registration: Patient Anxiety Reduction in Children by Using Simple Explanation Videos, ID: NCT0441377; www.clinicaltrials.gov, Data Sharing Statement: Deidentified individual participant data will not be made available.

Dataset Information

RandomizEd controlled trial for pre-operAtive dose-escaLation BOOST in locally advanced rectal cancer (RECTAL BOOST study): study protocol for a randomized controlled trial.

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RandomizEd controlled trial for pre-operAtive dose-escaLation BOOST in locally advanced rectal cancer (RECTAL BOOST study): study protocol for a randomized controlled trial.

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