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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
Sponsor:
Collaborator:
Maastro Clinic, The Netherlands
Information provided by (Responsible Party):
Helena M Verkooijen, 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.

Condition or disease Intervention/treatment Phase
Rectal Cancer Radiation: Boost Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 128 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: cohort multiple randomized controlled trial
Masking: None (Open Label)
Primary Purpose: Treatment
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

Arm Intervention/treatment
Experimental: 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.
Radiation: Boost
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.



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.


  3. 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).

  4. 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.

  5. 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.

  6. (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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • Participant in the PLCRC project (ClinicalTrials.gov: NCT02070146)
  • Informed consent obtained for being offered experimental interventions within the PLCRC project
  • Informed consent obtained for questionnaires on patient reported outcomes within the PLCRC project
  • WHO: 0-2
  • Indication for chemoradiation based on primary tumor, regional nodes, metastasis (TNM) stage
  • Referred for chemoradiation
  • No contra-indication for MRI
  • Tumor distance from ano-rectal transition ≤10 cm

Exclusion criteria

  • <18 years
  • No indication for chemoradiation according to Dutch guidelines based on TNM staging.
  • Inflammatory bowel disease
  • Prior pelvic radiotherapy
  • At least one contra-indication for Capecitabine administration (based on Dihydropyrimidine dehydrogenase (DPD)-deficiency, bloodcount, liver malfunction, renal failure (Creatinine clearance <30 ml/min), medical history such as recent cardiac events
  • Recent pregnancy ≤ 1 year ago
  • Inadequate understanding of the Dutch language in speech and/or writing

Information from the National Library of Medicine

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


Locations
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Netherlands
University Medical Center Utrecht
Utrecht, Netherlands, 3584 CX
Sponsors and Collaborators
UMC Utrecht
Maastro Clinic, The Netherlands
Investigators
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Principal Investigator: HM Verkooijen, MD PhD Imaging Division, UMC Utrecht
Principal Investigator: M. Berbee, MD PhD Radiation-Oncology, MAASTRO clinic
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Helena M Verkooijen, Principle Investigator, UMC Utrecht
ClinicalTrials.gov Identifier: NCT01951521    
Other Study ID Numbers: NL46051.041.13
First Posted: September 26, 2013    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019
Keywords provided by Helena M Verkooijen, UMC Utrecht:
Rectal cancer
Locally advanced rectal cancer
Radiotherapy
Boost
Dose-escalation
Pathological complete response
Response
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases