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

Rectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03259035
• Other study ID #: CO28
• Status: Completed
• Phase: Phase 2
• Start date: June 29, 2018
• Est. completion date: April 25, 2024

Study information

• Verified date: April 2024
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: April 25, 2024
• Est. primary completion date: April 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• Folfox Protocol
6 cycles of q2weekly FOLFOX, or
• Capox
4 cycles of q3weekly CAPOX

Locations

Country	Name	City	State
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	The Research Institute of the McGill University	Montreal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Health Sciences North	Sudbury	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	UC Irvine Medical Center	Orange	California
United States	Virginia Mason Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Canadian Cancer Trials Group

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 — View Citation

Outcome

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