- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03714490
MRI Simulation-guided Boost in Short-course Preoperative Radiotherapy for Unresectable Rectal Cancer (SUNRISE)
MRI Simulation-guided Boost in Short-course Preoperative Radiotherapy (SCPRT) Followed by Consolidation Chemotherapy Versus Long Course Chemoradiation for Unresectable Rectal Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The study is a prospective phase II randomized multicenter trial. The purpose of this study is to compare short-term radiotherapy with MRI simulation-guided boost followed by consolidation chemotherapy(Experimental group) with preoperative long-term chemoradiotherapy(Control group) for middle-lower unresectable locally advanced rectal cancer evaluated by MRI. The primary endpoint is the rate of R0 resection, and the secondary objectives are local recurrence-free survival, distant metastasis-free survival, disease-free survival and overall survival at 3-year and 5-year follow up. Furthermore, pathological complete response rate, the acute and late toxicity profile and quality of life (QOL) after 3 years follow-up are secondary endpoints. The exploratory end point includes the circulating tumor DNA, and other potential biomarkers from tumor tissue and blood sample for treatment response and survival predicting. For each group, a plan for collection of serum/plasma/feces at baseline and different stages during or after treatment and for obtaining fresh tumor tissue for freezing prior to treatment was defined in the protocol.
The SUNRISE-trial has been designed by National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, and the hypothesis is R0 resection rate in Experimental group was superior to that in Control group.
Interim analysis design: As a phase II trial, the safety of experimental intervention is a major concern. We took the toxicity data from STELLAR, a phase III randomized study led by our center, as a reference. The incidence of G3 and above side effects in the short course radiotherapy with sequential neoadjuvant chemotherapy group was 28%, and that in the standard long-course concurrent chemoradiotherapy control group was 5%. Considering that boost dose may increase toxicity, if severe toxicity in the study group significantly exceeds that in the control group by more than 35%, it is up to the principal investigator to decide whether to modify the study protocol or terminate the study. The sample size of the interim analysis was calculated by the Z-pooled test, with α=0.05 (one-sided test), 1-β=0.90, using PASS 11 software. The frequency of the toxicity of G3 and above should be compared when neoadjuvant therapy was completed in 21 patients enrolled in each group.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Jing Jin, M.D.
- Phone Number: 86-010-87788503
- Email: jinjing@csco.org.cn
Study Contact Backup
- Name: Wen-Yang Liu, M.D.
- Phone Number: 13810753633
- Email: liuwenyang26@163.com
Study Locations
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Beijing, China, 100021
- Recruiting
- Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Biopsy proven rectal adenocarcinoma;
- Distance between tumour and anal verge≤ 10cm;
- Locally advanced tumour;(AJCC Cancer Staging:T3, T4 or N+)
- Mesorectal fascia(MRF)+ or T4b evaluated by pelvic MRI;
- Eastern Cooperative Oncology Group(ECOG) performance score ≤ 1;
- Written informed consent;
- Mentally and physically fit for chemotherapy;
- Adequate blood counts: White blood cell count ≥3.5 x 109/L Haemoglobin levels ≥100g/L Platelet count ≥100 x 109/L Creatinine levels ≤1.0× upper normal limit(UNL) Urea nitrogen levels ≤1.0× upper normal limit(UNL) Alanine aminotransferase(ALT) ≤1.5× upper normal limit(UNL) Aspartate aminotransferase(AST) ≤1.5× upper normal limit(UNL) Alkaline phosphatase(ALP) ≤1.5× upper normal limit(UNL) Total bilirubin(TBIL) ≤1.5× upper normal limit(UNL)
- No excision of tumor, chemotherapy or other anti-tumor treatment after the diagnosis.
Exclusion Criteria:
- Distant metastases;
- Recurrent rectal cancer;
- Active Crohn's disease or ulcerative colitis;
- Concomitant malignancies;(except basocellular carcinoma or in-situ cervical carcinoma)
- Allergic to Fluorouracil or Platinum drugs;
- Contraindications to MRI for any reason;
- Concurrent uncontrolled medical condition;
- Pregnancy or breast feeding;
- Known malabsorption syndromes or lack of physical integrity of upper gastrointestinal tract;
- Symptoms or history of peripheral neuropathy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Experimental group
The intervention of Experimental group includes: Radiotherapy, followed by chemotherapy with capecitabine, oxaliplatin, and then surgery.
The detail of procedure: 1, short-course preoperative radiotherapy(SCPRT) , which consists of SCPRT, 5 Gray(Gy) x 5, 4Gy for boost on the gross tumour volume(GTV) with MRI-simulation alone; 2,then after 7-10 days of radiotherapy completed, patients will receive consolidation chemotherapy, given in 3 week cycle of capecitabine 1000 mg/m2 twice daily, day 1-14 combined with oxaliplatin 130 mg/m2 once.
In total, 4 cycles of neoadjuvant chemotherapy are prescribed preoperatively, then followed by a total mesorectal excision(TME) and postoperative adjuvant chemotherapy.
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Short-course preoperative radiotherapy(SCPRT) with neoadjuvant chemotherapy, which consists of SCPRT, 5 Gy x 5, 4Gy for boost on the GTV with MRI-simulation alone, then after 7-10 days of radiotherapy completed, patients will receive consolidation chemotherapy, given in 3 week cycle of capecitabine 1000 mg/m2 twice daily, day 1-14 combined with oxaliplatin 130 mg/m2 once.
In total, 4 cycles of neoadjuvant chemotherapy are scheduled before surgery.
Other Names:
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ACTIVE_COMPARATOR: Control group
The intervention of Control group includes:Radiotherapy, capecitabine, and surgery.
The detail of procedure: 1, long-term chemoradiotherapy(CRT), which consists of a long-term chemoradiation (2 Gy x 25 with capecitabine) preoperatively; 2, 6-8 weeks after chemoradiation, total mesorectal excision(TME) and then postoperative adjuvant chemotherapy.
The radiotherapy is given in combination with capecitabine in a dose of 825 mg/m2 twice daily on days when radiotherapy, excluding weekends.
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Long-term chemoradiotherapy(CRT), which consists of a long-term chemoradiation (2 Gy x 25 with capecitabine) preoperatively.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
R0(microscopically margin-negative) resection rate
Time Frame: 1-month after surgery completed
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the rate of microscopically margin-negative resection after neoadjuvant treatment
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1-month after surgery completed
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
local recurrence-free survival
Time Frame: 3-year and 5-year
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the time from surgery to local recurrence
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3-year and 5-year
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distant metastasis-free survival
Time Frame: 3-year and 5-year
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the time from diagnosis to metastasis
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3-year and 5-year
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disease-free survival
Time Frame: 3-year and 5-year
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the time from surgery to recurrence
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3-year and 5-year
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overall survival
Time Frame: 3-year and 5-year
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the time from diagnosis to death
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3-year and 5-year
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pathological complete response rate
Time Frame: 1-month after surgery completed
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pathological complete response in surgery specimen
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1-month after surgery completed
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the acute toxicity profile
Time Frame: 1-month
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the frequency of acute adverse events during and after treatment in 1-month, including gastrointestinal (vomiting, diarrhea and incontinence), dermatitis, and hematologic toxicity evaluated weekly by the Common Terminology Criteria 4.0.
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1-month
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the late toxicity profile
Time Frame: 3-year
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the late toxicity after treatment completion for 1-month, the frequency of late adverse events after 1-month of treatment, including gastrointestinal function, fistula, and hematologic toxicity, evaluated regularly by LENT-SOMA scoring systems.
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3-year
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general quality of life (QoL) by QLQ-30
Time Frame: 3-year
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general quality of life of patients evaluated by questionaire of EORTC QLQ-C30.
The higher score in total indicates the worse quality of life in general.
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3-year
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QoL by QLO-CR29
Time Frame: 3-year
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quality of life related to colorectal disease of patients evaluated by questionaire of EORTC QLQ-CR29.
The higher score in total of this module indicates the worse quality of life by colorectal module.
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3-year
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
circulating tumor DNA, and other potential biomarkers such as T-cell receptor
Time Frame: 3-year
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The exploratory end point for predicting of treatment response and survival.
The circulating tumor DNA test by sequencing will includes KRAS, NRAS, BRAF,PI3K,TP53,PTEN, EGFR, NEGF etc (509-gene panel).
And Measuring change in T cell receptor sub-types during treatment.
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3-year
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Collaborators and Investigators
Investigators
- Study Director: Jing Jin, M.D., National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Publications and helpful links
General Publications
- Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4.
- Chen W, Zheng R, Zeng H, Zhang S, He J. Annual report on status of cancer in China, 2011. Chin J Cancer Res. 2015 Feb;27(1):2-12. doi: 10.3978/j.issn.1000-9604.2015.01.06.
- Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rodel C, Cervantes A, Arnold D; ESMO Guidelines Committee. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv22-iv40. doi: 10.1093/annonc/mdx224. No abstract available. Erratum In: Ann Oncol. 2018 Oct 1;29(Suppl 4):iv263.
- Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Krynski J, Michalski W, Oledzki J, Kusnierz J, Zajac L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwolinski J, Winiarek M, Wisniowska K, Partycki M, Beczkowska K, Polkowski W, Stylinski R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Cisel B, Skorzewska M, Mielko J, Bebenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac L, Wojnar A, Lesniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kolodziejski L, Radkowski A, Zelazowska-Omiotek U, Czeremszynska B, Kepka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopylo R, Markiewicz W, Kedzierawski P, Wydmanski J; Polish Colorectal Study Group. Long-course oxaliplatin-based preoperative chemoradiation versus 5 x 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Ann Oncol. 2016 May;27(5):834-42. doi: 10.1093/annonc/mdw062. Epub 2016 Feb 15.
- Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Pahlman L, Wiig JN, Bystrom P, Bujko K, Glimelius B. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008 Aug 1;26(22):3687-94. doi: 10.1200/JCO.2007.15.3858.
- Burbach JP, den Harder AM, Intven M, van Vulpen M, Verkooijen HM, Reerink O. Impact of radiotherapy boost on pathological complete response in patients with locally advanced rectal cancer: a systematic review and meta-analysis. Radiother Oncol. 2014 Oct;113(1):1-9. doi: 10.1016/j.radonc.2014.08.035. Epub 2014 Oct 1.
- Teo MTW, McParland L, Appelt AL, Sebag-Montefiore D. Phase 2 Neoadjuvant Treatment Intensification Trials in Rectal Cancer: A Systematic Review. Int J Radiat Oncol Biol Phys. 2018 Jan 1;100(1):146-158. doi: 10.1016/j.ijrobp.2017.09.042. Epub 2017 Sep 29.
- Caravatta L, Padula GD, Picardi V, Macchia G, Deodato F, Massaccesi M, Sofo L, Pacelli F, Rotondi F, Cecere G, Sallustio G, Di Lullo L, Piscopo A, Mignogna S, Bonomo P, Cellini N, Valentini V, Morganti AG. Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: results of a phase II study. Acta Oncol. 2011 Nov;50(8):1151-7. doi: 10.3109/0284186X.2011.582880. Epub 2011 Aug 18.
- Engels B, Platteaux N, Van den Begin R, Gevaert T, Sermeus A, Storme G, Verellen D, De Ridder M. Preoperative intensity-modulated and image-guided radiotherapy with a simultaneous integrated boost in locally advanced rectal cancer: report on late toxicity and outcome. Radiother Oncol. 2014 Jan;110(1):155-9. doi: 10.1016/j.radonc.2013.10.026. Epub 2013 Nov 12.
- Lee JH, Kim DY, Nam TK, Yoon SC, Lee DS, Park JW, Oh JH, Chang HJ, Yoon MS, Jeong JU, Jang HS. Long-term follow-up of preoperative pelvic radiation therapy and concomitant boost irradiation in locally advanced rectal cancer patients: a multi-institutional phase II study (KROG 04-01). Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):955-61. doi: 10.1016/j.ijrobp.2012.01.045. Epub 2012 Apr 24.
- Li JL, Ji JF, Cai Y, Li XF, Li YH, Wu H, Xu B, Dou FY, Li ZY, Bu ZD, Wu AW, Tham IW. Preoperative concomitant boost intensity-modulated radiotherapy with oral capecitabine in locally advanced mid-low rectal cancer: a phase II trial. Radiother Oncol. 2012 Jan;102(1):4-9. doi: 10.1016/j.radonc.2011.07.030. Epub 2011 Sep 6.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Rectal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Capecitabine
- Oxaliplatin
Other Study ID Numbers
- NCC201807007
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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