Nivolumab in Preventing Colon Adenomas in Participants With Lynch Syndrome and a History of Partial Colectomy

NCT03631641 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: OSU-17198NCI-2018-01491
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colon Adenoma; Colon Carcinoma; Lynch Syndrome; MLH1 Gene Mutation; MSH2 Gene Mutation

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  At 3 years

Study Arms (1)

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.

Biological: Nivolumab

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• John Hays: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Trial stopped early due to withdrawal of pharmaceutical sponsor support

Results Point of Contact

• Title: Dr. John Hays
• Organization: The Ohio State University Comprehensive Cancer Center

John.Hays@osumc.edu

614-293-6529

Study Officials

• John Hays, MD, Ph.D

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: August 15, 2018
• Study Start: October 4, 2018
• Primary Completion: January 25, 2021
• Study Completion: January 25, 2021
• Last Updated: July 1, 2024
• Results First Posted: July 1, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)