Nivolumab and ADI-PEG 20 Before Surgery for the Treatment of Resectable Liver Cancer

NCT04965714 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-1198NCI-2021-06214
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effect of nivolumab and ADI-PEG 20 before surgery in treating patients with liver cancer that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. ADI-PEG 20 may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. Giving nivolumab and ADI-PEG 20 before surgery may help control liver cancer.

Conditions

Resectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events (AEs)

  Safety will be recorded through the incidence of AEs, serious (S)AEs and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will tabulate AEs with frequency and percentage and will summarize them by severity and their relations to the study treatments, and will estimate the success rate along with the 95% exact confidence interval.

  Up to 30 days post-treatment

• Rate of pathologic complete response

  Pathological response rate will be estimated along with the 95% confidence interval (95% CI).

  Up to 2 years post-treatment

• Necrosis of tumors

  Up to 2 years post-treatment

Secondary Outcomes (3)

• Time-to-progression (TTP)

  Up to 2 years post-treatment

• Recurrent-free survival (RFS)

  From surgery to date of a recurrent disease or date of death whichever occurs first if patients have an event, or to the last follow-up date if patients are alive without RD, assessed up to 2 years

• Overall survival (OS)

  From the initiation of the study combination to the date of death, assessed up to 2 years

Other Outcomes (1)

• Immune biomarker analysis

  Up to 2 years post-treatment

Study Arms (1)

Treatment (nivolumab, pegargiminase)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes on day 1 and pegargiminase IM at 2 days before day 1 of cycle 1, day 8 of cycle 1, days 1 and 8 of cycle 2, and day 1 of cycle 3. Treatments repeat every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection at week 7. A cycle is 14 days.

Biological: Nivolumab; Biological: Pegargiminase; Procedure: Resection

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (nivolumab, pegargiminase)

Pegargiminase BIOLOGICAL

Given IM

Also known as: ADI-PEG 20, pegylated arginine deiminase

Treatment (nivolumab, pegargiminase)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Treatment (nivolumab, pegargiminase)

Eligibility Criteria

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

You may qualify if:

• 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
• Must have histologically confirmed HCC (documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by AASLD (American Association for the Study for Liver Diseases) criteria in cirrhotic subjects (presence of non-rim arterial phase hyperenhancement relative to the liver parenchyma with venous washout for tumors \>= 1 cm). For subjects without cirrhosis, histological confirmation is mandatory. The determination of cirrhosis status will ultimately lie in the clinical judgment of the surgical oncologist and medical oncologist involved in the care of the patient
• Must be eligible for liver resection with curative intent; diagnosis must be confirmed by pathologist review of screening biopsy and 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
• 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 magnetic resonance imaging (MRI) or spiral computed tomography (CT) scan
• Allowed are prior treatments for HCC including prior surgery, radiation therapy, local-regional therapy (ablation or arterial directed therapies), or systemic therapy including sorafenib or chemotherapy. (Prior anti-PD-1 or ADI-PEG 20 therapies are not allowed)
• Must have Eastern Cooperative Oncology Group performance status (ECOG PS) score =\< 1
• Absolute neutrophil count \>= 1,500/uL (within 14 days of the first dose of study drug)
• Platelets \>= 100,000/uL (within 14 days of the first dose of study drug)
• Hemoglobin \> 9.0 g/dL (may be transfused or receive epoetin alfa \[e.g., Epogen\] to maintain or exceed this level) (within 14 days of the first dose of study drug)
• Total bilirubin =\< 1.5 mg/dL (within 14 days of the first dose of study drug)
• Serum creatinine =\< 1.5 times the upper limit of normal (ULN) or estimated creatinine clearance \> 40mL/min (within 14 days of the first dose of study drug)
• Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and/or alanine transaminase (ALT) ) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN (within 14 days of the first dose of study drug)
• Serum uric acid =\< 10 mg/dL (595 umol/L) (with or without medication control) (within 14 days of the first dose of study drug)
• Must be \>= 18 years of age
• 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 and every 4 weeks while taking nivolumab (for women of childbearing potential \[WOCBP\])

You may not qualify if:

• Has any other malignancy from which the patient has been disease-free for less than 2 years (exceptions: non-melanoma skin cancer or in situ carcinoma of any site are allowed)
• Has an organ allograft(s)
• Has 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 anticipates needing for a major surgical procedure during the course of the study (other than defined by protocol such as the pre-treatment fine needle aspirations or core biopsies) within 7 days prior to first dose of study drug
• Has a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) or a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's granulomatosis\])
• Has a history of testing positive for human immunodeficiency virus or has acquired immunodeficiency syndrome (AIDS)
• Has any underlying medical condition, which in the opinion of the investigator, will make the administration of study drug hazardous or will obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea
• Has a known risk factor for bowel perforation including a history of acute diverticulitis, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or gastrointestinal obstruction
• Has a primary brain tumor (excluding meningiomas and other benign lesions), any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, or (within the past year) a history of stroke
• Has a history of serious systemic disease, including myocardial infarction or unstable angina within the last 12 months; a 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
• Has a 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
• Is receiving a high dose steroid (e.g., \> 10 mg prednisone daily or equivalent) or other more potent immune suppression medications (e.g., infliximab)
• Has had influenza-, hepatitis-, or other vaccines within a month prior to initiation of study drugs
• Has had a clinical history of coagulopathy, bleeding diathesis or thrombosis within the past year
• Has a serious, non-healing wound, ulcer, or bone fracture
• Is pregnant (positive pregnancy test) or lactating

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

Nivolumab; ADI PEG20

Intervention Hierarchy (Ancestors)

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

Study Officials

• Sunyoung Lee

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 1, 2021
• First Posted: July 16, 2021
• Study Start: April 13, 2022
• Primary Completion: February 10, 2023
• Study Completion: February 10, 2023
• Last Updated: February 16, 2023

Record last verified: 2023-02

Locations

US (1)