Colon AdenomaPhase 2NCT03631641
Nivolumab in Preventing Colon Adenomas in Participants With Lynch Syndrome and a History of Partial Colectomy
A Phase 2 study testing Nivolumab in people with Colon Adenoma and Colon Carcinoma, run by John Hays at 1 site in United States.
Trial summary
This phase II trial studies how well nivolumab works in preventing colon adenomas in participants with Lynch syndrome and a history of surgery to remove part of the colon. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colon Adenoma, Colon Carcinoma, Lynch Syndrome
- What is being tested?
- Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Oct 2018to 25 Jan 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must have a diagnosis of Lynch syndrome confirmed by the identification of a germline mutation in MLH1 or MSH2.
- Patient must have a history of colon cancer or advanced colon adenoma requiring hemicolectomy with at least 60 cm of colon remaining without evidence of disease.
- Be willing and able to provide written informed consent/assent for the trial.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
- Absolute neutrophil count (ANC) >= 1,500 /mcL within 10 days of treatment initiation.
- Platelets >= 100,000 / mcL within 10 days of treatment initiation.
Show all 19Show fewer
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency within 10 days of treatment initiation.
- Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN within 10 days of treatment initiation.
- Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN within 10 days of treatment initiation.
- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases within 10 days of treatment initiation.
- Albumin >= 2.5 mg/dL within 10 days of treatment initiation.
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants within 10 days of treatment initiation.
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants within 10 days of treatment initiation.
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of study drug.
- Women must not be breastfeeding.
- WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with nivolumab plus 5 half-lives of nivolumab (19 weeks) plus 30 days (duration of ovulatory cycle) for a total of 23 weeks post-treatment completion.
- Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with nivolumab plus 5 half-lives of the study drug (19 weeks) plus 90 days (duration of sperm turnover) for a total of 31 weeks post-treatment completion.
- Hemicolectomy and adjuvant chemotherapy (if given) must be completed at least one year prior to study entry.
- All subjects must take at least 81 mg of aspirin per day. Daily doses up to 650 mg of aspirin per day will be accepted.
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Individuals who are receiving systemic steroid therapy at a stable dose less than or equal to 10 mg of prednisone per day or its equivalent will be permitted to participate.
- Has a known history of active TB (Bacillus tuberculosis).
- Hypersensitivity to nivolumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had hemicolectomy, prior chemotherapy, targeted small molecule therapy, or radiation therapy within one year prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent.
Show all 22Show fewer
- Note: Subjects with =< grade 2 neuropathy and/or alopecia are an exception to this criterion and may qualify for the study.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids exceeding 10 mg prednisone per day or its equivalent, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of, or any evidence of, active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject?s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Have a known history of a bleeding disorder or gastrointestinal ulceration that would preclude the use of a daily 81 mg aspirin.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding or is expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected).
- Has received a live vaccine within 30 days of planned start of study therapy.
- Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.
- Subjects with germline MSH6, PMS2, or EPCAM mutations will be excluded from participation.
- Prisoners or individuals who are compulsorily detained will be excluded from participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
Official title: A Phase II Study of PD-1 Inhibition for the Prevention of Colon Adenomas in Patients With Lynch Syndrome and a History of Partial Colectomy
This phase II trial studies how well nivolumab works in preventing colon adenomas in participants with Lynch syndrome and a history of surgery to remove part of the colon. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine if maintenance therapy with nivolumab can decrease the incidence of colon adenomas in a population of patients with genetic predisposition to colorectal cancer and a history of hemicolectomy due to colon cancer or advanced colon adenoma.
SECONDARY OBJECTIVES:
- To assess the safety of nivolumab maintenance therapy in this population. II. To obtain preliminary data on the short-term incidence of advanced colon adenomas (measuring greater than 10 mm or with high-grade dysplasia) and colon and non-colonic cancers in Lynch patients treated with maintenance nivolumab.
EXPLORATORY OBJECTIVES:
- To determine biomarkers of immunologic activity associated with biologic activity of nivolumab in this population.
OUTLINE:
Participants receive nivolumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 3 months for a total of 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at 3 months, every 6 months for 1 year, then every 12 weeks thereafter.
- Being tested
- Nivolumab
- Medical subject headings
- Colonic Neoplasms, Colorectal Neoplasms, Hereditary Nonpolyposis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabBiological
Also called BMS-936558, MDX-1106, NIVO, ONO-4538
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (nivolumab) | Experimental | Participants receive nivolumab intravenously IV over 60 minutes on day 1. Treatment repeats every 3 months for a total of 8 courses in the absence of disease progression or unacceptable toxicity. Receives: Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence Rate of Adenomas
The associated confidence intervals will be reported and used to determine if the incidence rate is significantly different from that reported among Lynch patients not receiving nivolumab, 0.33.
Measured: At 3 years
Incidence Rate of High-risk Adenomas
The associated confidence interval will be reported and used to determine if the incidence rate is significantly different from 0.22, the reported incidence of high-risk adenomas among Lynch syndrome patients not receiving nivolumab.
Measured: At 3 years
Incidence Rate of Colon Cancers
The incidence rates of colon cancers in Lynch patients treated with nivolumab will be estimated with corresponding confidence intervals.
Measured: At 3 years
Incidence Rate of Non-colonic Cancers
The incidence rates of non-colonic cancers in Lynch patients treated with nivolumab will be estimated with corresponding confidence intervals.
Measured: At 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2018
- Study start4 Oct 2018
- Primary completion25 Jan 2021
- Study completion25 Jan 2021
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colon AdenomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- John Hays
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, John Hays, Ohio State University Comprehensive Cancer Center
- Investigators
- John Hays, MD, Ph.D, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03631641
- Sponsor's protocol ID
- OSU-17198
- Other IDs
- NCI-2018-01491
- Status last verified
- Jun 2024
- First submitted
- 13 Aug 2018
- Last updated
- 1 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of PD-1 Inhibition for the Prevention of Colon Adenomas in Patients With Lynch Syndrome and a History of Partial Colectomy
- ClinicalTrials.gov ID
- NCT03631641
- Acronym / sponsor ID
- OSU-17198
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 3 participants (actual)
- Lead sponsor
- John HaysUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 4 Oct 2018 (actual)
- Primary completion
- 25 Jan 2021 (actual)
- Study completion
- 25 Jan 2021 (actual)
- First posted
- 15 Aug 2018 (actual)
- Results
- Posted 1 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well nivolumab works in preventing colon adenomas in participants with Lynch syndrome and a history of surgery to remove part of the colon. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread.
Detailed description
PRIMARY OBJECTIVES:
- To determine if maintenance therapy with nivolumab can decrease the incidence of colon adenomas in a population of patients with genetic predisposition to colorectal cancer and a history of hemicolectomy due to colon cancer or advanced colon adenoma.
SECONDARY OBJECTIVES:
- To assess the safety of nivolumab maintenance therapy in this population. II. To obtain preliminary data on the short-term incidence of advanced colon adenomas (measuring greater than 10 mm or with high-grade dysplasia) and colon and non-colonic cancers in Lynch patients treated with maintenance nivolumab.
EXPLORATORY OBJECTIVES:
- To determine biomarkers of immunologic activity associated with biologic activity of nivolumab in this population.
OUTLINE:
Participants receive nivolumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 3 months for a total of 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at 3 months, every 6 months for 1 year, then every 12 weeks thereafter.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (nivolumab) | Experimental | Biological: NivolumabParticipants receive nivolumab intravenously IV over 60 minutes on day 1. Treatment repeats every 3 months for a total of 8 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patient must have a diagnosis of Lynch syndrome confirmed by the identification of a germline mutation in MLH1 or MSH2.
- Patient must have a history of colon cancer or advanced colon adenoma requiring hemicolectomy with at least 60 cm of colon remaining without evidence of disease.
- Be willing and able to provide written informed consent/assent for the trial.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
- Absolute neutrophil count (ANC) >= 1,500 /mcL within 10 days of treatment initiation.
Key exclusion criteria (22 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Individuals who are receiving systemic steroid therapy at a stable dose less than or equal to 10 mg of prednisone per day or its equivalent will be permitted to participate.
- Has a known history of active TB (Bacillus tuberculosis).
- Hypersensitivity to nivolumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: BMS-936558, MDX-1106, NIVO, ONO-4538Given IV | Biological | Treatment (nivolumab) |
Primary outcome
Incidence Rate of Adenomas
Time frame: At 3 years
The associated confidence intervals will be reported and used to determine if the incidence rate is significantly different from that reported among Lynch patients not receiving nivolumab, 0.33.
Incidence Rate of High-risk Adenomas
Time frame: At 3 years
The associated confidence interval will be reported and used to determine if the incidence rate is significantly different from 0.22, the reported incidence of high-risk adenomas among Lynch syndrome patients not receiving nivolumab.
Incidence Rate of Colon Cancers
Time frame: At 3 years
The incidence rates of colon cancers in Lynch patients treated with nivolumab will be estimated with corresponding confidence intervals.
Incidence Rate of Non-colonic Cancers
Time frame: At 3 years
The incidence rates of non-colonic cancers in Lynch patients treated with nivolumab will be estimated with corresponding confidence intervals.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Colon Adenoma
Enrolling by invitation
Cold Snare Piecemeal Resection vs Cold Snare Endoscopic Mucosal Resection
Colon Polyp, Colon Adenoma
Enrolling by invitation
Six Versus Twelve Month Index Follow-up After Large Colon Polyp Resection
Colon Polyp, Adenoma
Recruiting
Comparison of Adenoma Detection Rate in 3D vs. 2D Surveillance Colonoscopy
Colonoscopy, Adenoma Detection Rate
Recruiting
Computer-Aided Water Exchange Colonoscopy With and Without Linked-Color Imaging for Detection of Clinically Significant Serrated Lesions
Sessile Colonic Polyp, Serrated Lesion
RecruitingObservational study
GelPOINT® Path-Assisted Endoscopic Removal of Colon and Rectal Polyps: A Feasibility and Safety Study
Polyp Colorectal, Rectal Adenoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Hays, MD, Ph.D principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab in people with Colon Adenoma and Colon Carcinoma, run by John Hays at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence Rate of Adenomas (time frame: At 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2024; AzTrials last refreshed its copy on 8 Nov 2026.