Clinical trial NCT03259035: NEO: Neoadjuvant Chemotherapy, Excision and Observation for Early Rectal Cancer
Official title: NEO: Neoadjuvant Chemotherapy, Excision and Observation for Early Rectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rectal Cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2017-08-23
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a two staged, single arm phase II trial of chemotherapy (FOLFOX or CAPOX) followed by tumour excision in patients with early stage rectal cancer
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to find out the effects of chemotherapy followed by less invasive surgery on patients and their early rectal cancer. The approach of this trial will be considered a success if at least 65% of participants are able to keep the rectum.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed invasive well-moderately differentiated rectal adenocarcinoma diagnosed within 90 days prior to enrollment.
* Tumour stage cT1-T3abN0 based on pelvic MRI

  * cT1N0- tumour invasion into submucosa, no radiographic evidence of mesorectal nodal metastasis, tumour deposits or vascular invasion.
  * cT2N0 - tumour invasion into muscularis propria, no radiographic evidence of mesorectal nodal metastasis, tumour deposits or vascular invasion.
  * cT3a,bN0- tumour invasion through the muscularis propria no more than 5 mm into the subserosa/perirectal tissue and clear of the circumferential radial margin (CRM). Absence of radiographic evidence of mesorectal nodal metastasis, tumour deposits or lymphovascular invasion.

Note: If the tumour is not visualized in the MRI but there is histological confirmation of rectal adenocarcinoma the patient is eligible.

* cN0 stage based on pelvic MRI. Any nodes ≥ 10 mm in longest dimension are considered malignant, regardless of nodal morphology. For pelvic nodes \< 10 mm in longest dimension, if nodes are seen and are deemed to be morphologically benign in the opinion of the radiologist and surgeon, the patient is eligible. Patients with visible pelvic sidewall nodes are excluded
* M0 stage based on no evidence of metastatic disease by CT imaging.
* Mid to low-lying tumour eligible for local tumour excision in the opinion of the treating surgeon.
* Age of at least 18 years.
* Medically fit to undergo radical surgery as per treating surgeon's discretion
* No contraindications to protocol chemotherapy.
* Adequate normal organ and marrow function as defined below (must be done within 30 days prior to enrolment):

  * ANC ≥ 1.5 x 109/L
  * platelet count ≥100 x 109/L
  * bilirubin \< 1.5 ULN, excluding Gilbert's syndrome
  * Calculated creatinine clearance of ≥ 50 ml/min.
  * Clearance to be calculated using Cockcroft formula: Males: 1.23 x (140 - age) x weight (kg) - serum creatinine (μmol/l) ; Females: 1.05 x (140 - age) x weight (kg) - serum creatinine (μmol/l)
* The patient must have an ECOG performance status of 0, 1.
* Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life and health utility questionnaires.
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
* Must be accessible for treatment and follow up. Patients registered on this trial must be treated with chemotherapy and followed at the enrolling centre.
* Protocol treatment is to begin within 5 working days of patient enrollment.
* Women/men of childbearing potential must have agreed to use a highly effective contraceptive method during and for 6 months after completion of chemotherapy.

Exclusion Criteria:

* Patient has pathologic high risk factors on either the initial biopsy specimen report or follow-up biopsy (if done): high histologic grade, mucinous histology, lymphatic or vascular invasion.
* History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
* Synchronous cancer.
* Prior treatment for rectal cancer.
* Previous pelvic radiation for any reason.
* Patients with known dihydropyrimidine dehydrogenase deficiency
* Treatment with other investigational drugs or anti-cancer therapy within 28 days prior to enrolment.
* Clinically significant (i.e. active) cardiovascular disease for example cerebro vascular accidents (\< 6 months prior to enrolment), myocardial infarction (\< 6 months prior to enrolment), unstable angina, New York Heart Association (NYHA) grade II or higher, congestive heart failure, serious cardiac arrhythmia requiring medication.
* Any contra-indications to undergo MRI imaging.

Primary outcomes:
measure: Percentage of Organ Preservation
timeFrame: 3 years
Secondary outcomes:
measure: Percentage of Locoregional Relapses at 3 Years
timeFrame: 3 years
measure: Percentage of Distant Relapse at 3 Years
timeFrame: 3 years
measure: Percentage of Disease Free at 3 Years
timeFrame: 3 years
measure: Rate of Intraoperative Complications
timeFrame: 1 day
Other outcomes:
Locations:
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Sudbury
country: Canada
facility: Health Sciences North
state: Ontario
city: Montreal
country: Canada
facility: The Research Institute of the McGill University
state: Quebec
Study officials:
affiliation: Virginia Mason Medical Centre, WA USA
name: Hagen Kennecke
role: STUDY_CHAIR
affiliation: St. Paul's Hospital, Vancouver BC
name: Carl Brown
role: STUDY_CHAIR
References:
citation: Kennecke HF, O'Callaghan CJ, Loree JM, Moloo H, Auer R, Jonker DJ, Raval M, Musselman R, Ma G, Caycedo-Marulanda A, Simianu VV, Patel S, Pitre LD, Helewa R, Gordon VL, Neumann K, Nimeiri H, Sherry M, Tu D, Brown CJ. Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results. J Clin Oncol. 2023 Jan 10;41(2):233-242. doi: 10.1200/JCO.22.00184. Epub 2022 Aug 18.