RECTAL BOOST Study

Not Applicable

• Conditions: Rectal Cancer
• Interventions: Radiation: Boost

• Registration Number: NCT01951521
• Lead Sponsor: UMC Utrecht

Brief Summary

Randomized controlled trial in which the effect is investigated of a radiation boost in addition to standard chemoradiation in patients with locally advanced rectal cancer on 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.

Detailed Description

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 Timeline

• Study First Submitted: 2013-09-18
• Study First Submitted QC: 2013-09-23
• Study First Posted: 2013-09-26
• Study Start: 2014-09-01
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-24
• Last Update Posted: 2019-09-25
• Primary Completion: 2020-12-01
• Study Completion: 2020-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 128

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Boost	Boost	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.

Primary Outcome Measures

Name	Time	Method
Complete response rate	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.

Secondary Outcome Measures

Name	Time	Method
Patient reported quality of life	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)	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).
Acute toxicity in common toxicity criteria for adverse events (CTCAE).	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).
(disease-free) survival	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.
Surgical complication	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.
Patient reported workability	at baseline and 3, 6, 12 and 24 months after treatment.	validated questionnaires. Patient reported outcome (workability) is measured by Workability index.

Trial Locations

Locations (1)

University Medical Center Utrecht; 🇳🇱 Utrecht, Netherlands