Sorafenib Plus Toripalimab for Unresectable HCC With Portal Vein Tumor Thrombus (STUHCCPVTT)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04069949|
Recruitment Status : Not yet recruiting
First Posted : August 28, 2019
Last Update Posted : October 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|Unresectable Hepatocellular Cancer Portal Vein Tumor Thrombus||Drug: sorafenib; toripalimab||Phase 1 Phase 2|
Investigators aimed to conduct an exploratory study- an open-label, single-arm and multi-center -to evaluate the efficacy and safety of sorafenib plus toripalimab for unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). The primary objectives are 6-month progression free survival (PFS) rate and safety. Secondary objectives include objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and duration of response. The study is divided into dose escalation stage and expansion stage.
Stage I (escalation stage) was designed to identify the dose-limiting toxicity (DLT) of the combination therapy. Subjects enrolled were divided into two cohorts. Subjects (n=3) in cohort A received oral sorafenib at doses of 400 mg once daily, in combination with intravenous toripalimab 240 mg on the first day, every 3 weeks. Subjects (n=3) in cohort B received oral sorafenib at doses of 400 mg twice daily, in combination with intravenous toripalimab 240 mg on the first day, every 3 weeks. If DLT does not occur within 42 days of the first administration, the dose is escalated. If one subject experienced DLTs, additional 3 subjects are enrolled at that level. Unless no DLT occurs, the next dose level test is continued.
Once ≥2 subjects in cohort A experienced DLT, the study is suspended in advance. If ≥2 subjects in cohort B experienced DLT, the dose of cohort A is recommended in expansion stage. If DLT does not occur in cohort B or only 1 of 6 subjects suffered DLT, the dose of cohort B is recommended in expansion stage.
For subjects who experienced DLT, if adverse events (AEs) return to normal or common terminology criteria for adverse events (CTCAE) level 1 within 2 weeks and researchers believe continuing treatment is beneficial to the subjects, they can continue treatment after dose adjustment. Otherwise, termination of treatment is suggested.
According to CTCAE version 4.0, DLT was defined as any grade ≥3 treatment-related toxicity occurring within the first 42 days of administration. Six to twelve patients will be included in this stage.
Stage II (Expansion stage): According to the expansion dose based on stage I, subjects are enlarged to 39. Subjects enrolled are treated with oral sorafenib in combination with toripalimab (every 3 weeks) until suffering progressive disease (PD) or un-tolerated toxicities. Previous literature indicated 6-month PFS rate for HCC with PVTT treated with sorafenib is about 20%. Investigators hypothesize sorafenib plus toripalimab could improve 6-month PFS rate to 40%. Software (PASS) is used to calculate the sample size (β=0.2，α=0.05). According to the results, 35 subjects should be enrolled. When 10% missing rate is considered, total subjects is 39.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||39 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||one-arm study|
|Masking:||None (Open Label)|
|Official Title:||An Exploratory Study of Sorafenib Plus Toripalimab for Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus|
|Estimated Study Start Date :||December 1, 2019|
|Estimated Primary Completion Date :||October 1, 2020|
|Estimated Study Completion Date :||October 1, 2021|
Experimental: sorafenib plus toripalimab
Stage I：Subjects (n=3) in cohort A received oral sorafenib (400 mg qd), in combination with intravenous toripalimab (240 mg d1, q3w). Subjects (n=3) in cohort B received oral sorafenib (400 mg bid) and the administration of toripalimab is consistent with cohort A. If dose-limiting toxicity (DLT) does not occur within 42 days of the first administration, the dose is escalated.
Stage II: According to the expansion dose based on stage I, subjects are enlarged to 39.
Drug: sorafenib; toripalimab
Stage I: cohort A: sorafenib 400 mg qd+ toripalimab 240 mg d1; q3w cohort B: sorafenib 400 mg bid, toripalimab 240 mg d1; q3w Stage II: According to the expansion dose based on stage I, subjects are enlarged to 39.
- 6-month Progression Free Survival rate [ Time Frame: up to 6 months ]Proportion of patients with Progression Free Survival in 6-month
- Incidence of Treatment-Emergent Adverse Event [ Time Frame: up to 6 months ]Any adverse events related with treatment with Sorafenib Plus Toripalimab
- Objective Response Rate [ Time Frame: up to 6 months ]Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients
- Disease Control Rate [ Time Frame: up to 6 months ]Proportion of patients with stable disease, complete response and partial response
- Progression Free Survival [ Time Frame: up to 6 months ]A duration from the date of initial treatment with Sorafenib Plus Toripalimab to disease progression (defined by RECIST 1.1) or death of any cause.
- Overall Survival [ Time Frame: up to 1 year ]Duration from the date of initial treatment with Sorafenib Plus Toripalimab to the date of death due to any cause.
- Duration of response [ Time Frame: From the date of study enrollment to the time of death from any cause, assessed up to 1 year ]time from first documented complete or partial response to radiologically confirmed disease progression or death from any cause.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04069949
|Contact: Qiu Li, Professoremail@example.com|
|Contact: Yu Yang, Associate Professorfirstname.lastname@example.org|
|Principal Investigator:||Qiu Li, Professor||West China Hospital|