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Patients With Rectal Cancer: a "Wait-and-see" Approach

Primary Purpose

Colorectal Carcinoma

Status

Recruiting

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Radical external beam radiotherapy

About this trial

This is an interventional treatment trial for Colorectal Carcinoma

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Pelvic MRI defined disease (at least one of the following):
- mesorectum involved or breached - includes involvement of adjacent organ (s) (T3-T4)
- involvement of muscularis propria (T2)
- extra-mural vascular invasion
- tumour deposit within the mesorectum
- one or more involved mesorectal lymph node
Patients are considered medically fit for oncologic resection
ECOG performance status 0 or 1
No evidence of established metastatic disease (CT chest and abdomen)
Absolute neutrophil count >1.5x109/L; platelets >100x109/L,
Serum transaminase <3 x ULN;
Adequate renal function (Cockroft Gault estimation >50 mL/min)
Bilirubin <1.5 x ULN
Ability to comply with oral medication
Willingness and ability to give informed consent and comply with treatment and follow up schedule
Age 18 or over

Exclusion Criteria:

Previous radiotherapy to the pelvis (including brachytherapy)
Enlarged extramesorectal nodes
Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction within 6 months of randomisation)
T1N0 disease without extra-mural venous invasion
Unequivocal evidence of metastatic disease (includes resectable metastases)
Major impairment of bowel function without defunctioning stoma/ileostomy (baseline grade 3 diarrhoea or clinically significant faecal incontinence)
History of another malignancy within the last 5 years except successfully treated basal cell cancer of skin or carcinoma in situ of uterine cervix.
Known dihydropyrimidine dehydrogenase deficiency
Known Gilberts disease (hyperbilirubinaemia)
Taking warfarin or phenytoin or sorivudine
Gastrointestinal disorder which would interfere with oral therapy and its bioavailability
Pregnant, lactating, or pre-menopausal women not using adequate contraception
Unfit to receive any study treatment or subsequent surgical resection

Sites / Locations

McGill University Health Centre- Cedars Cancer CentreRecruiting
McGill University Health Center-Cedars Cancer CentreRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Radical External Beam RT for Colorectal Ca

Arm Description

A single arm consisting of: Radical external beam RT dose of 54 Gy in 30fx with radiosensitizing chemotherapy as per institutional standard

Outcomes

Primary Outcome Measures

Feasibility of a "wait and see" approach

Rate of failure to achieve CR or the rate of recurrence after achieving CR

Secondary Outcome Measures

Full Information

NCT ID

NCT03001362

First Posted

December 14, 2016

Last Updated

October 23, 2023

Sponsor

McGill University Health Centre/Research Institute of the McGill University Health Centre

1. Study Identification

Unique Protocol Identification Number

NCT03001362

Brief Title

Patients With Rectal Cancer: a "Wait-and-see" Approach

Official Title

Radical External Beam Chemoradiation in Patients With Rectal Cancer: a "Wait-and-see" Approach

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 2015 (undefined)

Primary Completion Date

July 31, 2024 (Anticipated)

Study Completion Date

January 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

McGill University Health Centre/Research Institute of the McGill University Health Centre

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Patients with histologically proven adenocarcinoma of the rectum will receive pelvic radiotherapy to a dose of 45Gy in 25 fractions with a tumor boost to a dose of 9Gy in 5 fractions (thus total of 54Gy/30Fx to the primary tumor), combined with radio sensitizing chemotherapy. Patients will then be closely monitored, through endoscopy and imaging, for response to treatment and relapse. Salvage oncologic surgery to be offered if there is failure to achieve complete clinical response or in the event of a loco regional relapse.

Detailed Description

The combination of preoperative (chemo)radiotherapy and total mesorectal excision (TME) has been shown to reduce the risk of local recurrence in patients with resectable adenocarcinoma of the rectum. The improved local control rates come at the price of an increased risk of surgical complications, including a postoperative death rate of 2-8 percent which may reach 30 per cent at 6 months in those aged over 85 years, as well as long-term impact on anorectal, urinary and sexual function. Patients with cancers in the low rectum in close proximity to the sphincter muscles, may require a permanent stoma, which can be associated with high psychological morbidity. Preoperative chemoradiotherapy followed by a delay to resection can produce pathological complete responses. One review of phase II and III studies identified an overall pCR rate of 13.5%, but even higher rates of pCR have been observed with doses of radiotherapy exceeding 45 Gy . Certainly patients who proceed to radical surgery after achieving a pCR with chemo radiation do have favorable long-term outcomes. But do patients whose tumor has already been sterilized by chemo radiotherapy need to proceed with radical surgery? A number of studies have now emerged highlighting the rationale of a 'wait and see' policy for patients who achieve a complete clinical response (cCR) after chemo radiotherapy. The majority of the clinical data supporting this approach have come from Brazil. The Brazilian data suggests that observation of such patients yields survival rates similar to those of patients who undergo radical surgery with confirmation of pCR. More recent studies from the United Kingdom and the Netherlands appear to support the feasibility of this approach. To date there is no published prospectively collected data of a wait-and-see policy from a North American Centre.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Radical External Beam RT for Colorectal Ca

Arm Type

Experimental

Arm Description

A single arm consisting of: Radical external beam RT dose of 54 Gy in 30fx with radiosensitizing chemotherapy as per institutional standard

Intervention Type

Radiation

Intervention Name(s)

Radical external beam radiotherapy

Other Intervention Name(s)

Radiosensitizing chemotherapy

Intervention Description

pelvic radiotherapy to a dose of 45 Gy in 25 fractions with a tumor boost to a dose of 9 Gy in 5 fractions (thus total of 54 Gy/30 fractions to the primary tumor), combined with radio sensitizing chemotherapy.

Primary Outcome Measure Information:

Title

Feasibility of a "wait and see" approach

Description

Rate of failure to achieve CR or the rate of recurrence after achieving CR

Time Frame

One year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Pelvic MRI defined disease (at least one of the following): mesorectum involved or breached - includes involvement of adjacent organ (s) (T3-T4) involvement of muscularis propria (T2) extra-mural vascular invasion tumour deposit within the mesorectum one or more involved mesorectal lymph node Patients are considered medically fit for oncologic resection ECOG performance status 0 or 1 No evidence of established metastatic disease (CT chest and abdomen) Absolute neutrophil count >1.5x109/L; platelets >100x109/L, Serum transaminase <3 x ULN; Adequate renal function (Cockroft Gault estimation >50 mL/min) Bilirubin <1.5 x ULN Ability to comply with oral medication Willingness and ability to give informed consent and comply with treatment and follow up schedule Age 18 or over Exclusion Criteria: Previous radiotherapy to the pelvis (including brachytherapy) Enlarged extramesorectal nodes Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction within 6 months of randomisation) T1N0 disease without extra-mural venous invasion Unequivocal evidence of metastatic disease (includes resectable metastases) Major impairment of bowel function without defunctioning stoma/ileostomy (baseline grade 3 diarrhoea or clinically significant faecal incontinence) History of another malignancy within the last 5 years except successfully treated basal cell cancer of skin or carcinoma in situ of uterine cervix. Known dihydropyrimidine dehydrogenase deficiency Known Gilberts disease (hyperbilirubinaemia) Taking warfarin or phenytoin or sorivudine Gastrointestinal disorder which would interfere with oral therapy and its bioavailability Pregnant, lactating, or pre-menopausal women not using adequate contraception Unfit to receive any study treatment or subsequent surgical resection

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Neil Kopek, M.D.

Phone

514-934-4440

neil.kopek@muhc.mcgill.ca

First Name & Middle Initial & Last Name or Official Title & Degree

Marianna Perna, CCRP,CCRC

Phone

514-934-1934

Ext

43191

marianna.perna@muhc.mcgill.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Neil Kopek, M.D.

Organizational Affiliation

Radiation Oncologist

Official's Role

Principal Investigator

Facility Information:

Facility Name

McGill University Health Centre- Cedars Cancer Centre

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H4A 3J1

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Neil Kopek, M.D.

Phone

514-934-4440

neil.kopek@muhc.mcgill.ca

First Name & Middle Initial & Last Name & Degree

Marianna Perna, CCRP, CCRC

Phone

514-934-1934

Ext

43191

marianna.perna@muhc.mcgill.ca

First Name & Middle Initial & Last Name & Degree

Neil Kopek, M.D.

Facility Name

McGill University Health Center-Cedars Cancer Centre

City

Montréal

State/Province

Quebec

ZIP/Postal Code

H4A 3J1

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marianna Perna, CCRP,CCRC

Phone

514-934-1934

Ext

43191

marianna.perna@muhc.mcgill.ca

First Name & Middle Initial & Last Name & Degree

Tatiana Carvalho, CCRP

Phone

514-934-1934

Ext

43698

tatiana.carvalho@muhc.mcgill.ca

First Name & Middle Initial & Last Name & Degree

Sergio Faria, M.D.

First Name & Middle Initial & Last Name & Degree

Tarek Hijal, M.D.

First Name & Middle Initial & Last Name & Degree

Caroline Reinhart, M.D.

First Name & Middle Initial & Last Name & Degree

Giovanni Artho, M.D.

First Name & Middle Initial & Last Name & Degree

Jamil Asselah, M.D.

First Name & Middle Initial & Last Name & Degree

Ragu Rajan, M.D.

First Name & Middle Initial & Last Name & Degree

Marie Van-Huyse, M.D.

First Name & Middle Initial & Last Name & Degree

Sender Lieberman, M.D.

First Name & Middle Initial & Last Name & Degree

Patrick Charlebois, M.D.

12. IPD Sharing Statement

Plan to Share IPD

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Patients With Rectal Cancer: a "Wait-and-see" Approach

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