Nivolumab With or Without Ipilimumab in Treating Patients With Resectable Liver Cancer

NCT03222076 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2017-0097NCI-2018-01106
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the side effects and how well nivolumab with or with ipilimumab works in treating patients with liver cancer that can be removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Hepatocellular Carcinoma; Resectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of Presurgical Nivolumab With or Without Ipilimumab, Defined as the Number of Participants With of Adverse Events.

  The frequency of adverse events, serious adverse events (grade ≥3), and laboratory abnormalities. Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Safety will be recorded through the incidence of adverse events, serious adverse events and specific laboratory abnormalities (worst grade) in each treatment arm.

  Up to 5 years

Secondary Outcomes (3)

• Objective Response Rate

  After 6 weeks of therapy, up to 5 years

• Time to Progression

  Up to 5 years

• Progression Free Survival (PFS)

  Up to 5 years

Study Arms (2)

Arm A (nivolumab)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo liver surgery on day 1 of week 7. Beginning 4 weeks after surgery, patients continue nivolumab IV over 30 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Nivolumab

Arm B (ipilimumab, nivolumab)

EXPERIMENTAL

Patients receive ipilimumab IV over 90 minutes on day 1 and nivolumab as Arm A. Treatment repeats every 2 weeks for up to 3 cycles for nivolumab in the absence of disease progression or unacceptable toxicity. Patients undergo liver surgery on day 1 of week 7. Beginning 4 weeks after surgery, patients receive ipilimumab IV over 90 minutes every 6 weeks and nivolumab IV over 30 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Biological: Nivolumab

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Arm B (ipilimumab, nivolumab)

Nivolumab BIOLOGICAL

Given IV

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

Arm A (nivolumab); Arm B (ipilimumab, nivolumab)

Eligibility Criteria

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

You may qualify if:

• Patients must give written informed consent prior to initiation of therapy, in keeping with the policies of the institution. Patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy.
• Target population
• Patients with histologically confirmed HCC (Documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by AASLD criteria in cirrhotic subjects is required (presence of arterial hypervascularity with venous washout). For subjects without cirrhosis, histological confirmation is mandatory. The determination of resectability status will ultimately lie in the clinical judgment of the surgical oncologist and medical oncologist involved in the care of the patient.
• Patient must have measurable disease defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures ≥ 15 mm with conventional techniques or ≥ 10 mm with more sensitive techniques such as MRI or spiral CT scan.
• Patient can have had prior treatment for HCC including prior surgery, radiation therapy, local-regional therapy (abalation or arterial directed therapies), and systemic therapy including sorafenib or chemotherapy (but not anti-PD-1 or anti-CTLA-4 therapy)
• ECOG performance status ≤ 1.
• Within 14 days of the first dose of study drug, patients must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,500/μL
• Platelets ≥100,000/μL
• Hgb \> 9.0 g/dL (may be transfused or receive epoetin alfa \[e.g., Epogen®\] to maintain or exceed this level)
• Total bilirubin ≤ 1.5 mg/dl
• Serum creatinine ≤ 1.5 times the upper limit of normal or estimated CrCL \>40mL/min.
• AST (SGOT) and/or ALT (SGPT) ≤ 5 X institutional upper limit of normal Age and Sex
• Men and women ≥ 18 years of age
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.

You may not qualify if:

• Any of the following criteria will disqualify the patient from participation:
• Target Disease Exceptions
• Any other malignancy from which the patient has been disease-free for less than 2 years, except for non-melanoma skin cancer, or in situ carcinoma of any site.
• Medical History and Concurrent Disease
• Patients who have organ allografts.
• Patients who have had a major surgical procedure, open biopsy, or significant traumatic injury with poorly healed wound within 6 weeks prior to first dose of study drug; or anticipation of need for major surgical procedure during the course of the study (other than defined by protocol); fine needle aspirations or core biopsies within 7 days prior to first dose of study drug. NOTE: Patients will be allowed to start cycle 1 day 1 therapy after 24 hours from pre-treatment biopsy.
• Autoimmune disease: Patients with a history of inflammatory bowel disease (including crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., wegener's granulomatosis\]).
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Any underlying medical condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea.
• Patients who have had a history of acute diverticulitis, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis which are known risks factors for bowel perforation, should be excluded from the study.
• Patients who have a primary brain tumor (excluding meningiomas and other benign lesions), any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, or history of stroke within the past year.
• History of serious systemic disease, including myocardial infarction or unstable angina within the last 12 months, history of hypertensive crisis or hypertensive encephalopathy, uncontrolled hypertension (blood pressure of \>140/90 mmHg) at the time of enrollment, New York Heart Association (NYHA) Grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), significant vascular disease or symptomatic peripheral vascular disease.
• Patients who have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
• Patients who are on high dose steroid (e.g. \> 10 mg prednisone daily or equivalent) or other more potent immune suppression medications (e.g. infliximab)
• Patients who have had influenza, hepatitis, or other vaccines within a month prior to initiation of study drugs.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Kaseb AO, Hasanov E, Cao HST, Xiao L, Vauthey JN, Lee SS, Yavuz BG, Mohamed YI, Qayyum A, Jindal S, Duan F, Basu S, Yadav SS, Nicholas C, Sun JJ, Singh Raghav KP, Rashid A, Carter K, Chun YS, Tzeng CD, Sakamuri D, Xu L, Sun R, Cristini V, Beretta L, Yao JC, Wolff RA, Allison JP, Sharma P. Perioperative nivolumab monotherapy versus nivolumab plus ipilimumab in resectable hepatocellular carcinoma: a randomised, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022 Mar;7(3):208-218. doi: 10.1016/S2468-1253(21)00427-1. Epub 2022 Jan 20.

  PMID: 35065057 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Results Point of Contact

• Title: Dr. Ahmed Kaseb
• Organization: MD Anderson Cancer Center

akaseb@mdanderson.org

(713) 792-2828

Study Officials

• Ahmed O Kaseb

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: July 19, 2017
• Study Start: September 28, 2017
• Primary Completion: September 14, 2022
• Study Completion: September 14, 2022
• Last Updated: July 10, 2023
• Results First Posted: July 10, 2023

Record last verified: 2023-06

Locations

US (1)