NEO: Neoadjuvant Chemotherapy, Excision and Observation for Early Rectal Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Folfox Protocol; Drug: Capox

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA - Vancouver Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII Health Sciences Centre
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute
    • Sudbury, Ontario, Canada, P3E 5J1
      • Health Sciences North
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • The Research Institute of the McGill University
• United States
  • California
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
  • Washington
    • Seattle, Washington, United States, 97101
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: chemotherapy (FOLFOX or CAPOX) followed by tumour excision	Drug: Folfox Protocol; 6 cycles of q2weekly FOLFOX, or; Drug: Capox; 4 cycles of q3weekly CAPOX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of organ preservation rate	The primary endpoint of this study is the protocol specified organ preservation rate, defined as the proportion of patients with tumour downstaging to ypT0/T1good N0 and who avoid radical surgery. The 95% confidence interval for the organ preservation rate will be calculated	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Locoregional Relapse Rate (LRR)	3 years
Distant Relapse Rate (DRR) estimated based on Kaplan-Meier method	3 years
Disease Free Survival (DFS) estimated based on Kaplan-Meier method	3 years
Rate of post-operative complications	3 years
Number and severity of adverse events using CTCAE V5	3 years
Quality of Life using QLQ-C30	3 years
Cost effectiveness using the EQ-5D-5L questionnaire	3 years

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Investigators: Study Chair: Hagen Kennecke, Virginia Mason Medical Centre, WA USA; Study Chair: Carl Brown, St. Paul's Hospital, Vancouver BC

Publications and helpful links

General Publications

• 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.

Helpful Links

• Journal of Clinical Oncology CO.28 Primary Endpoint Results

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2018
• Primary Completion (Actual): April 8, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: August 21, 2017
• First Submitted That Met QC Criteria: August 21, 2017
• First Posted (Actual): August 23, 2017

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: CO28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No