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

• ClinicalTrials.gov Identifier: NCT03259035
• Recruitment Status: Active, not recruiting
• First Posted: August 23, 2017
• Last Update Posted: May 21, 2020
• Sponsor: Canadian Cancer Trials Group
• Information provided by (Responsible Party): Canadian Cancer Trials Group

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Rectal Cancer	Drug: Folfox Protocol; Drug: Capox	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 58 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• 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
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: NEO: Neoadjuvant Chemotherapy, Excision and Observation for Early Rectal Cancer
• Actual Study Start Date: August 22, 2017
• Estimated Primary Completion Date: September 30, 2020
• Estimated Study Completion Date: March 31, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Measurement of organ preservation rate [ Time Frame: 3 years ]
   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

Secondary Outcome Measures :

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

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, California

UC Irvine Medical Center

Orange, California, United States, 92868

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02115

United States, Washington

Virginia Mason Medical Center

Seattle, Washington, United States, 97101

Canada, British Columbia

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada, V5Z 4E6

St. Paul's Hospital

Vancouver, British Columbia, Canada, V6Z 1Y6

Canada, Manitoba

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Nova Scotia

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada, B3H 1V7

Canada, Ontario

Kingston Health Sciences Centre

Kingston, Ontario, Canada, K7L 2V7

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada, K1H 8L6

Health Sciences North

Sudbury, Ontario, Canada, P3E 5J1

Canada, Quebec

The Research Institute of the McGill University

Montreal, Quebec, Canada, H4A 3J1

Sponsors and Collaborators

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

More Information

• Responsible Party: Canadian Cancer Trials Group
• ClinicalTrials.gov Identifier: NCT03259035
• Other Study ID Numbers: CO28
• First Posted: August 23, 2017
• Last Update Posted: May 21, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases