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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| chemotherapy (FOLFOX or CAPOX) followed by tumour excision | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Folfox Protocol | Drug | 6 cycles of q2weekly FOLFOX, or |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Organ Preservation | Defined as the percentage of patients with tumour downstaging to ypT0/T1good N0 and who avoid radical surgery. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Locoregional Relapses at 3 Years | Locoregional relapse is defined as reappearance of a tumour within the rectum or pelvis. The percentage of loco-reginal relapse at 3 years was estimated by Kaplan-Meier method for the survival function of the loco-regional relapse free survival, defined as the time from enrollment to the first date of definitive evidence (clinical, radiological or pathological) of locoregional relapses with patients who developed distant relapse only, died, loss to follow up, or were alive at clinical cut-off censored at respectively at last date of distant relapses, date of death, date of lost to follow-up, or last disease assessment date. |
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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
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):
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:
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| Name | Affiliation | Role |
|---|---|---|
| Hagen Kennecke | Virginia Mason Medical Centre, WA USA | Study Chair |
| Carl Brown | St. Paul's Hospital, Vancouver BC | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC Irvine Medical Center | Orange | California | 92868 | United States | ||
| Dana-Farber Cancer Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35981270 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Chemotherapy (FOLFOX or CAPOX) Followed by Tumour Excision | FOLFOX infusion on a 14 day cycle (IV oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 over 2 hours on day 1 and bolus fluorouracil 400 mg/m2 over 5 - 15 minutes and continuous infusion of fluorouracil 2400 mg/m2 over 46 to 48 hours on days 1-2) for a total of 6 cycles or CAPOX on a 21 day cycle (IV oxaliplatin 130 mg/m2 over 2 hours on day 1 and 1000 mg/m2 capecitabine orally twice daily for 14 days from day 1) for a total of 4 cycles. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stage 1: Chemotherapy |
| |||||||||||||
| Stage 2: Tumor Excision |
|
All participants enrolled in this study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Chemotherapy (FOLFOX or CAPOX) Followed by Tumour Excision | FOLFOX infusion on a 14 day cycle (IV oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 over 2 hours on day 1 and bolus fluorouracil 400 mg/m2 over 5 - 15 minutes and continuous infusion of fluorouracil 2400 mg/m2 over 46 to 48 hours on days 1-2) for a total of 6 cycles or CAPOX on a 21 day cycle (IV oxaliplatin 130 mg/m2 over 2 hours on day 1 and 1000 mg/m2 capecitabine orally twice daily for 14 days from day 1) for a total of 4 cycles. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Organ Preservation | Defined as the percentage of patients with tumour downstaging to ypT0/T1good N0 and who avoid radical surgery. | All participants who had chemotherapy. | Posted | Number | 90% Confidence Interval | percentage of participants | 3 years |
|
During chemotherapy treatment (maximum 24 weeks)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Chemotherapy (FOLFOX or CAPOX) Followed by Tumour Excision | FOLFOX infusion on a 14 day cycle (IV oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 over 2 hours on day 1 and bolus fluorouracil 400 mg/m2 over 5 - 15 minutes and continuous infusion of fluorouracil 2400 mg/m2 over 46 to 48 hours on days 1-2) for a total of 6 cycles or CAPOX on a 21 day cycle (IV oxaliplatin 130 mg/m2 over 2 hours on day 1 and 1000 mg/m2 capecitabine orally twice daily for 14 days from day 1) for a total of 4 cycles. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Laryngeal edema | Respiratory, thoracic and mediastinal disorders | CTCAE (V5.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Watering eyes | Eye disorders | CTCAE (V5.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Chris O'Callaghan | Canadian Cancer Trials Group | 6135336430 | cocallaghan@ctg.queensu.ca |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 21, 2020 | May 30, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 2, 2020 | May 30, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
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| ID | Term |
|---|---|
| C410216 | Folfox protocol |
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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
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| Capox | Drug | 4 cycles of q3weekly CAPOX |
|
| 3 years |
| Percentage of Distant Relapse at 3 Years | Distant relapse is defined as appearance of rectal cancer disease at sites remote from the rectum. The percentage of distant relapse at 3 years was estimated also by Kaplan-Meier method for the survival function of the distant free survival, defined as the time from enrollment to the first date of definitive evidence (clinical, radiological or pathological) of distant relapses with patients who died, loss to follow up, or were alive at clinical cut-off censored at respectively: date of death, date of lost to follow-up, and last disease assessment date. | 3 years |
| Percentage of Disease Free at 3 Years | Percentage of disease free at 3 years was estimated by Kaplan-Meier method for the survival function of Disease-Free Survival (DFS), which is defined as the interval from date of enrollment to the first date of the events defined below:
| 3 years |
| Rate of Intraoperative Complications | Percentage of patients with at least one intraoperative injury | 1 day |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| Virginia Mason Medical Center | Seattle | Washington | 97101 | United States |
| BCCA - Vancouver Cancer Centre | Vancouver | British Columbia | V5Z 4E6 | Canada |
| St. Paul's Hospital | Vancouver | British Columbia | V6Z 1Y6 | Canada |
| CancerCare Manitoba | Winnipeg | Manitoba | R3E 0V9 | Canada |
| QEII Health Sciences Centre | Halifax | Nova Scotia | B3H 1V7 | Canada |
| Health Sciences North | Greater Sudbury | Ontario | P3E 5J1 | Canada |
| Kingston Health Sciences Centre | Kingston | Ontario | K7L 2V7 | Canada |
| Ottawa Hospital Research Institute | Ottawa | Ontario | K1H 8L6 | Canada |
| The Research Institute of the McGill University | Montreal | Quebec | H4A 3J1 | Canada |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Percentage of Locoregional Relapses at 3 Years | Locoregional relapse is defined as reappearance of a tumour within the rectum or pelvis. The percentage of loco-reginal relapse at 3 years was estimated by Kaplan-Meier method for the survival function of the loco-regional relapse free survival, defined as the time from enrollment to the first date of definitive evidence (clinical, radiological or pathological) of locoregional relapses with patients who developed distant relapse only, died, loss to follow up, or were alive at clinical cut-off censored at respectively at last date of distant relapses, date of death, date of lost to follow-up, or last disease assessment date. | All patients enrolled | Posted | Number | 95% Confidence Interval | percentage of participants | 3 years |
|
|
|
| Secondary | Percentage of Distant Relapse at 3 Years | Distant relapse is defined as appearance of rectal cancer disease at sites remote from the rectum. The percentage of distant relapse at 3 years was estimated also by Kaplan-Meier method for the survival function of the distant free survival, defined as the time from enrollment to the first date of definitive evidence (clinical, radiological or pathological) of distant relapses with patients who died, loss to follow up, or were alive at clinical cut-off censored at respectively: date of death, date of lost to follow-up, and last disease assessment date. | All participants enrolled | Posted | Number | 95% Confidence Interval | percentage of participants | 3 years |
|
|
|
| Secondary | Percentage of Disease Free at 3 Years | Percentage of disease free at 3 years was estimated by Kaplan-Meier method for the survival function of Disease-Free Survival (DFS), which is defined as the interval from date of enrollment to the first date of the events defined below:
| All participants enrolled. | Posted | Number | 95% Confidence Interval | percentage of participants | 3 years |
|
|
|
| Secondary | Rate of Intraoperative Complications | Percentage of patients with at least one intraoperative injury | Patients who had BOTH chemotherapy and tumor excision with transanal endoscopic microsurgery (TEM) or transanal minimally invasive surgery (TAMIS) | Posted | Number | percentage of participants | 1 day |
|
|
|
| 2 |
| 58 |
| 1 |
| 58 |
| 58 |
| 58 |
| Abdominal pain | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Bloating | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Mucositis oral | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Other gastrointestinal disorders | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Rectal hemorrhage | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Rectal pain | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Facial pain | General disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Fever | General disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Skin infection | Infections and infestations | CTCAE (V5.0) | Systematic Assessment |
|
| Weight loss | Investigations | CTCAE (V5.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Muscle cramp | Musculoskeletal and connective tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Other musculoskeletal and connective tissue disorder | Musculoskeletal and connective tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Dysesthesia | Nervous system disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Depression | Psychiatric disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Hoarseness | Respiratory, thoracic and mediastinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Laryngopharyngeal dysesthesia | Respiratory, thoracic and mediastinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Erythema multiforme | Skin and subcutaneous tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Other skin and subcutaneous tissue disorders | Respiratory, thoracic and mediastinal disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Flushing | Vascular disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (V5.0) | Systematic Assessment |
|
| Thromboembolic event | Vascular disorders | CTCAE (V5.0) | Systematic Assessment |
|
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| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |