Nivolumab and ADI-PEG 20 Before Surgery for the Treatment of Resectable Liver Cancer
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|ClinicalTrials.gov Identifier: NCT04965714|
Recruitment Status : Recruiting
First Posted : July 16, 2021
Last Update Posted : April 15, 2022
|Condition or disease||Intervention/treatment||Phase|
|Resectable Hepatocellular Carcinoma||Biological: Nivolumab Biological: Pegargiminase Procedure: Resection||Phase 2|
I. To evaluate the safety and tolerability of therapy and assess the pathologic response rate including pathologic complete response (pCR) and degree of necrosis (> 50% in tumor volume) with nivolumab + pegargiminase (ADI-PEG 20) in resectable hepatocellular carcinoma (HCC) in the context of presurgical therapy.
I. To assess the efficacy of presurgical nivolumab + ADI-PEG 20 therapy in HCC by estimating the time-to-progression (TTP), recurrence-free survival (RFS), and overall survival (OS).
I. To assess the immunological/biomarker changes (pre- versus [vs] post-treatment) in tumor tissues and peripheral blood in response to nivolumab + ADI-PEG 20 in HCC therapy.
II. To explore any potential association between these biomarker measures and antitumor response and immune-related response criteria (irRC) assessed by MD Anderson Department of Diagnostic Imaging.
Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and pegargiminase intramuscularly (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.
After completion of study treatment, patients are followed up at 30 days, then every 12 weeks for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pre-Operative Study Evaluating Nivolumab Plus ADI-PEG 20 in Patients With Resectable Hepatocellular Carcinoma|
|Actual Study Start Date :||April 13, 2022|
|Estimated Primary Completion Date :||April 30, 2024|
|Estimated Study Completion Date :||April 30, 2024|
Experimental: Treatment (nivolumab, pegargiminase)
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.
Undergo surgical resection
Other Name: Surgical Resection
- Incidence of adverse events (AEs) [ Time Frame: Up to 30 days post-treatment ]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.
- Rate of pathologic complete response [ Time Frame: Up to 2 years post-treatment ]Pathological response rate will be estimated along with the 95% confidence interval (95% CI).
- Necrosis of tumors [ Time Frame: Up to 2 years post-treatment ]
- Time-to-progression (TTP) [ Time Frame: Up to 2 years post-treatment ]TTP is defined as the time from the start of study drug to the first documented tumor progression or recurrence of tumor as determined by the investigator using Response Evaluation Criteria in Solid Tumors 1.1 or Immune-Related Response Criteria (irRC) criteria. Will be estimated by the Kaplan-Meier method.
- Recurrent-free survival (RFS) [ Time Frame: 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 ]RFS will be estimated by the Kaplan-Meier method.
- Overall survival (OS) [ Time Frame: From the initiation of the study combination to the date of death, assessed up to 2 years ]OS will be estimated by the Kaplan-Meier method.
- Immune biomarker analysis [ Time Frame: Up to 2 years post-treatment ]Will use descriptive statistics to summarize expressions of markers at each time point and will use paired t-test or Wilcoxon signed rank test to evaluate the pre- and post- treatment changes in immune biomarkers, including CD8+/Treg ratio. To correlate markers with response, will fit logistic regression models or use a Fisher's exact test. For longitudinal measurements, we will use logistic regression models including random effects to account for within-patient correlation. To evaluate marker changes over time, will fit linear mixed models with random effects to account for within-patient correlation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04965714
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Sunyoung Lee 713-792-8501 firstname.lastname@example.org|
|Principal Investigator: Sunyoung Lee|
|Principal Investigator:||Sunyoung Lee||M.D. Anderson Cancer Center|