RECTAL BOOST Study (RECTAL BOOST)
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|ClinicalTrials.gov Identifier: NCT01951521|
Recruitment Status : Active, not recruiting
First Posted : September 26, 2013
Last Update Posted : September 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|Rectal Cancer||Radiation: Boost||Not Applicable|
Rationale: The current treatment for locally advanced rectal cancer consists of pre-operative chemoradiation treatment (CRT) (50 Gray (Gy) in 25 fractions) followed by surgical resection, according to T-/N-stage, circumferential resection margin (CRM) and tumor localization (see table 1). After this neo-adjuvant treatment approximately 15% of patients show pathological complete response (pCR), i.e.no residual tumor in the resected specimen on pathologic examination. Patients with pCR have a lower risk of local and distant recurrences and significantly longer disease-free and overall survival. Furthermore, in these patients surgery could possibly have been omitted. Selected patients with a clinical complete response (cCR), defined prior to surgery by rectoscopy, rectal examination and magnetic resonance imaging (MRI), may opt for an organ-preserving therapy, a so called wait and see approach.
Response to chemoradiation occurs in a dose dependent fashion. Therefore, recent trials aimed to improve prognosis by radiation dose-escalation that resulted in improved pCR rates. Toxicity rates associated with radiation doses above 60 Gy are manageable and differ between studies; from increased to comparable or even lower toxicity. Moreover, dose escalation may increase the proportion of patients eligible for organ-preserving therapy.
Objective: We study whether addition of a radiation boost to standard chemoradiation in patients with locally advanced rectal cancer increases the complete response rate defined as pathological complete response, in those who undergo surgery, or 2-years local recurrence-free survival (2y-LRFS), in those who opted for a wait and see approach. Secondary objectives are adverse events due to chemoradiation (acute, perioperative and late toxicity), tumor response assessed with MRI, the impact of the boost on local and distant recurrence and survival as well as patient-reported quality of life and workability. The need for this comprehensive study is emphasized by the sub-optimal (radiation-) methods, heterogeneity between and poor reporting in the few previous trials in this field.
Study design: Multicentre Randomized Controlled Trial, nested within a prospective cohort according to the 'cohort multiple randomized controlled trial' (cmRCT) design.
Study population: Rectal cancer patients participating in a prospective cohort (the PLCRC project) and diagnosed with adenocarcinoma of the rectum whom will undergo chemoradiation based on clinical criteria (see table 1 section 1.2.1).
Intervention: An irradiation boost of 15 Gy delivered to the gross tumor volume (GTV) in 5 fractions in addition to the standard chemoradiation treatment of 50 Gy. Thereby increasing the total GTV dose to 65 Gy.
Main study parameters/endpoints: The primary endpoint is complete response either defined as pathological complete response (pCR) in patients who undergo surgery, assessed by standardized pathologic examination of the surgical specimen, or 2-years local recurrence-free survival (LRFS) after chemoradiation in patients who opted for a wait and see approach. Secondary outcomes are treatment acute, perioperative and late toxicity, tumor response assessed with MRI, patient-reported quality of life and workability, local recurrence and (disease-specific) survival.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||128 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||cohort multiple randomized controlled trial|
|Masking:||None (Open Label)|
|Official Title:||RandomizEd Controlled Trial for Pre-operAtive Dose-escaLation BOOST in Locally Advanced Rectal Cancer|
|Actual Study Start Date :||September 1, 2014|
|Estimated Primary Completion Date :||December 1, 2020|
|Estimated Study Completion Date :||December 1, 2020|
Boost radiation consists of 5 fractions of 3 Gy (total 15 Gy) delivered to the tumor (Gross Tumor Volume) additional to standard chemoradiation of 50 Gy with Capecitabine.
External Beam radiation delivered using intensity modulation radiation therapy (IMRT) planning, consisting of 15 Gy (in 5 sequential fractions).
No Intervention: Standard chemoradiation
Standard chemoradiation consisting of 25 x 2 Gy (total 50 Gy) with Capecitabine.
- Complete response rate [ Time Frame: pathologic examination following surgery, at aproximately 13-15 weeks (control arm) or 14-16 weeks (boost arm) after randomization or clinical complete respons of 2 years after first response assessment. ]The primary endpoint is complete response either defined as pathological complete response (pCR) in patients who undergo surgery, assessed by standardized pathologic examination of the surgical specimen, or 2-years local recurrence-free survival (LRFS) after chemoradiation in patients who opted for a wait and see approach.
- Acute toxicity in common toxicity criteria for adverse events (CTCAE). [ Time Frame: Until surgery at 8-10 weeks post chemoradiation (which is 13-15 weeks (control) or 14-16 weeks (boost) post randomization ]Outcomes are assessed according to Common Toxicity Criteria for Adverse Events (CTCAE) (v4.0).
- Patient reported quality of life [ Time Frame: at baseline and 3, 6, 12 and 24 months after treatment. ]
at baseline and 3, 6, 12 and 24 months after treatment. Patient reported outcome (Quality of life (QoL)) is measured by validated questionnaires.
QoL: European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR-29 (these acronyms indicate cancer and colorectal cancer specific questionnaires.
- Tumor response on Magnetic resonance imaging (MRI) [ Time Frame: at week 2 during chemoradiation and week 7 post chemoradiation. ]During (week 2) and after (7-8 weeks post) chemoradiation tumor response is assessed by (several) MRI (sequences such as T1, T2 and DWI).
- Patient reported workability [ Time Frame: at baseline and 3, 6, 12 and 24 months after treatment. ]validated questionnaires. Patient reported outcome (workability) is measured by Workability index.
- Surgical complication [ Time Frame: untill 30 days after surgery, which is 17-19 weeks (control) or 18-20 weeks (boost) post randomization ]Dutch Surgical Colorectal Audit criteria for surgical complication. This includes wound-infection, wound-healing (time), hospitalization (time), supportive treatment.
- (disease-free) survival [ Time Frame: up to death of included patients, for a maximum of 60 years post-randomization. ]Survival is measured, as well as other clinical data, in the PICNIC Cohort (ProspectIve data CollectioN Initiative on Colorectal cancer) reviewed by Dutch Medical Ethics Committee @ University Medical Center Utrecht, under number 12-510.
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): NCT01951521
|University Medical Center Utrecht|
|Utrecht, Netherlands, 3584 CX|
|Principal Investigator:||HM Verkooijen, MD PhD||Imaging Division, UMC Utrecht|
|Principal Investigator:||M. Berbee, MD PhD||Radiation-Oncology, MAASTRO clinic|