Description:
The aim of this study is to elucidate the utility of the immune checkpoint inhibitor
pembrolizumab in preventing the recurrence of HCC when administered before and after curative
surgery or ablation.
Title
- Brief Title: Pembrolizumab as Neoadjuvant Treatment in HCC
- Official Title: Neoadjuvant Treatment in the Prevention of Recurrence of Hepatocellular Carcinoma With Pembrolizumab Trial (AURORA)
Clinical Trial IDs
- ORG STUDY ID:
AURORA study
- NCT ID:
NCT03337841
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Pembrolizumab | MK-3475, Keytruda | Pembrolizumab |
Purpose
The aim of this study is to elucidate the utility of the immune checkpoint inhibitor
pembrolizumab in preventing the recurrence of HCC when administered before and after curative
surgery or ablation.
Detailed Description
Each subject will participate in the trial from the time he or she signs the informed consent
form until the final contact. After a screening phase of up to 28 days, each subject will
receive administration of pembrolizumab 200mg IV once only before curative treatment such as
hepatic resection or radiofrequency ablation, and will receive curative treatment after
administration of pembrolizumab. After curative treatment, each subject will receive
pembrolizumab 200mg IV every 3 weeks. Treatment will continue until tumor recurrence,
occurrence of an unacceptable adverse event, or the 16th treatment with pembrolizumab.( The
setting of 16 times administration is the period of adjuvant therapy of this trial is 12
month(=48weeks), administration of pembrolizumab is Q3W, so 16 times administration comes to
48 weeks.) Subjects who discontinue for reasons other than tumor recurrence will have
post-treatment follow-up visits for monitoring disease status until tumor recurrence, until
initiation of non-study cancer treatment, until withdrawal of consent for study
participation, or until becoming lost to follow-up. All subjects will be followed for overall
survival until death, withdrawal of consent for study participation, or the end of the study,
whichever comes first. After the end of trial treatment, each subject will be followed for 30
days for adverse event monitoring. Serious adverse events will be collected for 90 days after
the end of treatment or for 30 days after the end of treatment if the subject initiates new
anticancer therapy, whichever is earlier.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Pembrolizumab | Experimental | Pembrolizumab 200 mg IV once only in the neoadjuvant phase. Pembrolizumab 200 mg IV every 3 weeks in the adjuvant phase. | |
Eligibility Criteria
Inclusion Criteria:
- Hepatocellular carcinoma for which radical cure is possible by resection or RFA.
- Diagnosed with typical HCC based on imaging findings with Intermediate or High Risk of
recurrence as assessed by tumor characteristics.
- Male or female subjects >/= 20 years of age
- Child-Pugh score A
- ECOG Performance Status of 0.
- Adequate bone marrow, liver and renal function
Exclusion Criteria:
- Recurrent HCC
- HCC with extrahepatic metastasis and/or vascular invasion confirmed by diagnostic
imaging
- Subjects with poorly controlled ascites (excluding cases that responded to diuretic
therapy)
- Subjects with hepatic encephalopathy
- Past history of immunotherapy
- Past history or complication of an active autoimmune disorder.
- Past history or complication of interstitial pneumonia.
- Past or current history of malignant tumor, except for curative cases
- Subjects with renal insufficiency requiring hemodialysis or peritoneal dialysis.
- Past or current history of severe cardiovascular disease
- Active clinically serious infections except for HBV or HCV
- Subjects with convulsive disorder requiring treatment (risk of convulsive seizures).
- Subjects with gastrointestinal bleeding causing clinical problems within a 4-week
period before enrollment in this study.
- Subjects with thrombosis or embolism that developed within a 6-month period before
enrollment in this study
- Subjects with pregnant or breast feeding, or planning to become a parent
- Subjects with possible allergic reaction to the investigational drug.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 20 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | One-year recurrence-free survival rate |
| Time Frame: | 1 year after curative treatment |
| Safety Issue: | |
| Description: | One-year recurrence-free survival rate is defined as the recurrence-free survival rate 1year after curative treatment. |
Secondary Outcome Measures
| Measure: | Recurrence free survival |
| Time Frame: | From the date of enrollment until the date of first recurrence or date of death from any cause, whichever came first, up to 72 weeks. |
| Safety Issue: | |
| Description: | Recurrence-free survival is defined as the length of time from the date of confirmation of complete cure to the earliest of the following: the date when recurrence is diagnosed or the date of death due to any cause. |
| Measure: | Overall survival |
| Time Frame: | From date of enrollment until the date of death from any cause, up to 72 weeks. |
| Safety Issue: | |
| Description: | Overall survival is defined as the length of time from the date of confirmation of complete cure to the date of death due to any cause. |
| Measure: | Objective response rate after neoadjuvant phase |
| Time Frame: | Evaluation period is just before curative treatment, up to 4 weeks. |
| Safety Issue: | |
| Description: | Tumor assessment in accordance with RECIST1.1 will be performed after neoadjuvant administration. |
| Measure: | Tumor markers |
| Time Frame: | From the date of enrollment until the date of last administration of study drug, up to 72 weeks. |
| Safety Issue: | |
| Description: | Baseline levels of tumor markers including AFP, AFP-L3, and PIVKA-II and changes in their levels will be exploratory investigated in relation to the therapy efficacy. |
| Measure: | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] |
| Time Frame: | From the date of enrollment until the date of last administration of study drug, thereafter up to 4 months |
| Safety Issue: | |
| Description: | The safety endpoints of this study are the safety of pembrolizumab as neoadjuvant and/or adjuvant therapy in patients with HCC. To determine the safety of the drug, the degree of toxicity is evaluated in accordance with the CTCAE (version 4.0). |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Unknown status |
| Lead Sponsor: | Kindai University |
Trial Keywords
- Hepatocellular carcinoma
- Neo adjuvant chemotherapy
- Adjuvant chemotherapy
- Immune checkpoint inhibitor
- Pembrolizumab
Last Updated
November 9, 2017
