Colonoscopy for Colorectal Cancer

(NordICC Trial)

Recruiting at 6 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Oslo University Hospital

Must not be taking: Cytotoxic, Radiotherapy, Warfarin

Disqualifiers: Colorectal surgery, Severe cardiac, Lung, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

95000 Participants Needed

Trial Summary

What is the purpose of this trial?

Colorectal cancer (CRC) is a major burden in western countries. The disease develops from precursor lesions during a long time-interval. Colonoscopy can detect and remove CRC precursor lesions and may thus be effective for CRC prevention. Many national and international health organisations demand evidence from randomised trials to reduce incidence or mortality of the target disease before advocating population-wide cancer screening. However, while colonoscopy screening for the prevention of colorectal cancer is established in the United States and several European countries, no randomised trials exist to quantify the possible benefit of colonoscopy screening. NordICC is a randomised trial investigating the effect of colonoscopy on CRC incidence and mortality. NordICC is a multicentre, randomised trial in Nordic countries, the Netherlands and Poland. A minimum of 66 000 individuals, age 55-64 years, are drawn randomly from the population registries in the participating countries. 22 000 are invited for once-only colonoscopy (2:1 randomisation). Expected work-load with 50% compliance will be 11,000 colonoscopies. At the screening examination, all detected lesions are biopsied and removed whenever possible. The remaining 44 000 individuals (control group) are not offered any screening examination (care as usual).The primary study aims are CRC incidence and CRC mortality after 15 years of follow-up, with an interim analysis after 10 years of follow-up. In an intention-to-treat approach, a risk reduction of CRC mortality of 25% in the colonoscopy screening group compared to the control group is expected after 10 years follow-up, estimating 50% compliance in the screening group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on lifelong anticoagulant therapy with Warfarin, you would be excluded from participating.

What data supports the effectiveness of the treatment Colonoscopy, Colon Examination, Lower GI Endoscopy for colorectal cancer?

Research shows that colonoscopy can reduce the chances of getting and dying from colorectal cancer, although its effectiveness may vary depending on the part of the colon being examined and the skill of the person performing it. ^{1 2 3 4 5}

Is colonoscopy generally safe for humans?

Colonoscopy is generally considered a safe procedure, with major adverse events occurring at a low rate of 2.8 per 1000 screenings. However, serious issues like bleeding and perforation are more common when removing polyps (growths in the colon). ^{6 7 8 9 10}

How is colonoscopy different from other treatments for colorectal cancer?

Colonoscopy is unique because it not only helps detect colorectal cancer early but also allows for the removal of precancerous lesions during the same procedure, which can prevent the cancer from developing. Unlike other treatments that may only address existing cancer, colonoscopy serves both as a diagnostic and preventive tool. ^{11 12 13 14 15}

Research Team

Hans-Olov Adami, MD PhD

Principal Investigator

Harvard School of Public Health, Boston, USA

Michael Bretthauer, MD PhD

Principal Investigator

Oslo University Hospital

Michal Filip Kaminski, MD PhD

Principal Investigator

Marie Cure Sklodowska Cancer Center

Eligibility Criteria

This trial is for individuals aged 55-64 living in certain Northern-European countries, who haven't had colorectal surgery or cancer treatments recently. People with severe heart or lung disease, those needing constant care, or on lifelong Warfarin can't join.

Inclusion Criteria

I am between 55 and 64 years old and live in the screening area.

Exclusion Criteria

Return of unopened letter of invitation and/or reminder (address unknown)

I am currently receiving chemotherapy or radiotherapy for cancer.

You do not live in the country where the clinical trial is taking place.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Not specified

1 visit (in-person)

Colonoscopy Screening

Participants in the screening group undergo a one-time colonoscopy to detect and remove CRC precursor lesions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for CRC incidence and mortality over a long-term period

15 years

Interim analysis at 10 years

Treatment Details

Interventions

• Colonoscopy

Trial Overview The study tests if a one-time colonoscopy can reduce the incidence and mortality of colorectal cancer. Participants are randomly chosen to either receive a colonoscopy or no screening (usual care) and followed for up to 15 years.

Participant Groups

Group I: Colonoscopy screening Experimental Treatment 1 Intervention

One-time colonoscopy is the screening tool used in this trial. All individuals in the screening group will be offered a full colonoscopy. At colonoscopy, all detected CRC precursor lesions will be removed, whenever possible.

Group II: Control Active Control 1 Intervention

The control group will not be offered any screening or intervention within the trial, but follow usual care in the participating countries. Individuals assigned to the control group will not be informed about their status as controls in the trial. This approach facilitates a truly population-based study, which will be used to estimate the effect of the screening intervention in the general population, mimicking national CRC screening programs. All ethics committees at the participating centres have approved the study protocol before recruiting individuals to the trial. In Sweden, the national ethics committee particularly reviewed the non-information of the control group and found it ethically acceptable.

Colonoscopy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Colonoscopy for:

• Colorectal cancer screening
• Polyp removal
• Investigation of lower gastrointestinal symptoms

Approved in United States as Colonoscopy for:

• Colorectal cancer screening
• Polyp removal
• Investigation of lower gastrointestinal symptoms

Approved in Canada as Colonoscopy for:

• Colorectal cancer screening
• Polyp removal
• Investigation of lower gastrointestinal symptoms

Approved in Japan as Colonoscopy for:

• Colorectal cancer screening
• Polyp removal
• Investigation of lower gastrointestinal symptoms

Approved in China as Colonoscopy for:

• Colorectal cancer screening
• Polyp removal
• Investigation of lower gastrointestinal symptoms

Approved in Switzerland as Colonoscopy for:

• Colorectal cancer screening
• Polyp removal
• Investigation of lower gastrointestinal symptoms

Who Is Running the Clinical Trial?

Oslo University Hospital

Lead Sponsor

Trials

1,132

Recruited

7,856,000+

Maria Sklodowska-Curie National Research Institute of Oncology

Collaborator

Trials

81

Recruited

179,000+

Erasmus Medical Center

Collaborator

Trials

742

Recruited

2,156,000+

Landspitali University Hospital

Collaborator

Trials

46

Recruited

467,000+

Uppsala University Hospital

Collaborator

Trials

188

Recruited

749,000+

Karolinska Institutet

Collaborator

Trials

1,510

Recruited

32,450,000+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Harvard School of Public Health (HSPH)

Collaborator

Trials

283

Recruited

17,030,000+

Findings from Research

Colonoscopy is generally safe, with an adverse event rate of 2.8 per 1000 procedures, but serious complications like hemorrhage and perforation are more common when polypectomy is performed.

The article emphasizes the importance of preventing and managing adverse events specifically related to polypectomy and endoscopic mucosal resection of colonic lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events related to colonic endoscopic mucosal resection and polypectomy. Sethi, A., Song, LM.[2022]

In a study of 161 patients with lower gastrointestinal bleeding (LGIB) and 161 matched non-GIB controls, adverse events during bowel preparation and colonoscopy were found to be low, indicating that colonoscopy is generally safe for LGIB patients.

There were no significant differences in adverse events between LGIB and non-GIB patients, even among subgroups such as the elderly or those with comorbidities, suggesting that colonoscopy does not increase risks in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events during Bowel Preparation and Colonoscopy in Patients with Acute Lower Gastrointestinal Bleeding Compared with Elective Non-Gastrointestinal Bleeding. Niikura, R., Nagata, N., Shimbo, T., et al.[2022]

A structured assessment of 1,144 patients who underwent colonoscopy revealed that nearly 30% reported definite-related minor adverse events, and about 3% experienced major adverse events, indicating that post-procedural complications are more common than previously thought.

Patients who experienced definite-related adverse events were less likely to be willing to return for future colonoscopies and had a less positive overall experience, highlighting the importance of addressing these events to improve patient satisfaction and compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The incidence of 30-day adverse events after colonoscopy among outpatients in the Netherlands. de Jonge, V., Sint Nicolaas, J., van Baalen, O., et al.[2015]

In a study of 3121 asymptomatic veterans who underwent colonoscopy screening, adverse events occurred in only 2.8% of follow-up examinations, indicating that long-term colonoscopy screening is generally safe.

Serious cardiopulmonary events were the most common major complications, and a history of prior colonoscopic adverse events significantly increased the risk of future complications, suggesting the importance of assessing patients' medical histories before follow-up procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal assessment of colonoscopy adverse events in the prospective Cooperative Studies Program no. 380 colorectal cancer screening and surveillance cohort. Kobe, EA., Sullivan, BA., Qin, X., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Risk of colorectal cancer after colonoscopy compared with flexible sigmoidoscopy or no lower endoscopy among older patients in the United States, 1998-2005. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Patterns of endoscopic follow-up after surgery for nonmetastatic colorectal cancer. [2007]

3. United States pubmed.ncbi.nlm.nih.gov

Colon PillCam: why not just take a pill? [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Colonoscopy and colorectal cancer incidence and mortality. [2013]

5. England pubmed.ncbi.nlm.nih.gov

ScotCap - A large observational cohort study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Adverse events related to colonic endoscopic mucosal resection and polypectomy. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Adverse Events during Bowel Preparation and Colonoscopy in Patients with Acute Lower Gastrointestinal Bleeding Compared with Elective Non-Gastrointestinal Bleeding. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Colonoscopy-related adverse events and mortality in an Italian organized colorectal cancer screening program. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

The incidence of 30-day adverse events after colonoscopy among outpatients in the Netherlands. [2015]

10. United States pubmed.ncbi.nlm.nih.gov

Longitudinal assessment of colonoscopy adverse events in the prospective Cooperative Studies Program no. 380 colorectal cancer screening and surveillance cohort. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Evaluation of results of lower gastrointestinal endoscopic biopsi. [2020]

12. Australia pubmed.ncbi.nlm.nih.gov

Role of magnifying colonoscopy for diagnosis of colorectal neoplasms: From the perspective of Japanese colonoscopists. [2017]

13. France pubmed.ncbi.nlm.nih.gov

[The main indications for lower endoscopies]. [2006]

14. Ghana pubmed.ncbi.nlm.nih.gov

Endoscopic evaluation of the colorectum in patients presenting with haematochezia at korle-bu teaching hospital accra. [2022]

15. United States pubmed.ncbi.nlm.nih.gov

Benefits and limitations of cap-fitted colonoscopy in screening colonoscopy. [2021]