A Study of Pembrolizumab and Bavituximab in Patients With Advanced Hepatocellular Carcinoma
|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: NCT03519997|
Recruitment Status : Recruiting
First Posted : May 9, 2018
Last Update Posted : September 9, 2019
|First Submitted Date ICMJE||April 26, 2018|
|First Posted Date ICMJE||May 9, 2018|
|Last Update Posted Date||September 9, 2019|
|Actual Study Start Date ICMJE||April 26, 2018|
|Estimated Primary Completion Date||April 1, 2020 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Overall Response Rate [ Time Frame: 36 months ]
To determine the overall response rate (ORR) of combination pembrolizumab and bavituximab in patients with advanced HCC.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT03519997 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures
||Treatment response [ Time Frame: 36 months ]
To determine treatment response with pre- and intra-treatment biopsies and plasma/serum. Correlative studies will be performed on the collected tissue and blood samples to determine if predictive markers of response can be generated
|Original Other Pre-specified Outcome Measures||Same as current|
|Brief Title ICMJE||A Study of Pembrolizumab and Bavituximab in Patients With Advanced Hepatocellular Carcinoma|
|Official Title ICMJE||A Phase II Study of Pembrolizumab and Bavituximab in Patients With Advanced Hepatocellular Carcinoma|
|Brief Summary||This is a non-randomized, open-label, multi-site phase II therapeutic trial of pembrolizumab and bavituximab in patients with locally advanced HCC. Locally advanced or metastatic HCC is defined as disease that is not amenable to surgical and/or locoregional therapies. Subjects must not have received prior systemic therapy for advanced HCC in keeping with the first-line setting of this study.|
This is a non-randomized, open-label, multi-site phase II therapeutic trial of pembrolizumab and bavituximab in patients with locally advanced HCC. Locally advanced or metastatic HCC is defined as disease that is not amenable to surgical and/or locoregional therapies. Subjects must not have received prior systemic therapy for advanced HCC in keeping with the first-line setting of this study. Overall response rate (ORR) as assessed by the investigators and using RECIST 1.1 criteria, will be the primary endpoint.
Prior to initiation on treatment, all patients will sign an informed consent form. Only patients with histological proved HCC will be eligible for treatment. Tissue, either from archival formalin fixed paraffin embedded samples or a new biopsy of a target lesion will be needed.
Study therapy is defined as treatment with both pembrolizumab and bavituximab. Patients will receive trial treatment until disease progression, unacceptable toxicity, death or discontinuation from the study treatment for any other reason. Subjects will be allowed to continue study therapy after an initial investigator-assessed RECIST 1.1 defined progression as long as they meet the following criteria: 1) investigator assessed clinical benefit and 2) subject is tolerating study therapy. Subjects will be discontinued from study therapy upon the evidence of further progression, defined as an additional 10% or greater increase in tumor burden from time of initial progression (including all target lesions and new measurable lesions). New lesions are considered measurable if the longest diameter is at least 10 mm (except for pathological lymph nodes, which must have a short axis of at least 15 mm). Any new lesion considered non-measurable may become measurable and therefore included in the tumor burden measurement if the longest diameter increases to at least 10 mm (except for pathological lymph nodes, which must have an increase in short axis to at least 15 mm. For statistical analyses that include the investigator-assessed progression date, subjects who continue treatment beyond initial investigator-assessed, RECIST 1.1-defined progression will be considered to have investigator-assessed progressive disease at the time of the initial progressive event irrespective of confirmation on subsequent imaging. Patients will be followed for survival regardless of treatment discontinuation for any reason, unless they withdraw their consent to be followed for survival.
The treatment phase for each patient will begin on the initiation of study drug on Cycle 1 Day 1 (C1D1). Patients will continue study treatment until disease progression (or until discontinuation of study therapy in patient receiving pembrolizumab and bavituximab beyond progression), discontinuation due to toxicity, withdrawal of consent, or the study ends. A safety follow-up is mandatory at 30 days post the last dose.
Efficacy, safety, and correlative assessments will be performed as outlined in the Schedule of Visits and Procedures (section 6.0). Safety assessments will include hematology, biochemistry, and thyroid tests as well as ongoing evaluations of adverse events. Tumor response will be assessed radiographically every 9 weeks for the first 54 weeks, then every 12 weeks thereafter until disease progression (or until discontinuation of study therapy in patients receiving pembrolizumab or bavituximab beyond progression), loss to follow-up, or withdrawal of consent. Patients with radiological progression using RECIST may continue on study treatment if in the investigator's assessment the patient is experiencing clinical benefit and tolerating the treatment.
Dose Limiting Toxicity:
Initially, enrollment will be limited to 10 patients with no more than two patients enrolled per week. A safety committee comprised of the investigators and institutional GI Disease Orientated Team will monitor the occurrence of dose limiting toxicities (DLTs) for the first 10 patients prior to enrolling the remainder of the trial. The period for evaluating DLTs will be from the time of the first administration of study treatment through Study Day 28. DLTs will follow the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
If three or more DLTs occur during this period, enrollment will be suspended and the safety committee will make a determination of whether to reduce the bavituximab dose to 1 mg/kg. After the DLT safety assessment period for the initial 10 patients, enrollment may proceed for the remainder of the trial provided at least one patient has either a complete or partial response by RECIST 1.1 and patient safety will be evaluated on a regular basis by the institutional data safety monitoring committee (DSMC). A DLT will be defined as any treatment related toxicity in the list below that occurs during the DLT evaluation period. Toxicity that is clearly and directly related to the primary disease or to another etiology is excluded from this definition. The following will be considered DLTs:
The definition excludes the following conditions:
Survival follow-up phase
Patients who are no longer receiving any study treatments and have experienced disease progression will enter survival follow-up, regardless of whether they have initiated subsequent anticancer therapy. Survival follow-up information (by chart review, phone call or clinic visits) will be collected approximately every 3 months until death, loss to follow-up, withdrawal of consent or study termination.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Intervention Model Description:
Locally advanced or metastatic HCC not amenable to locoregional therapyMasking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Hepatocellular Carcinoma|
|Study Arms ICMJE||Experimental: Pembro + Bavi
Pembrolizumab 200 mg IV every 3 weeks plus, Bavituximab 3mg/kg IV weekly
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||April 1, 2021|
|Estimated Primary Completion Date||April 1, 2020 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
HBV-HCC: Controlled (treated) hepatitis B subjects will be allowed if they meet the following criteria:
Antiviral therapy for HBV must be given for at least 12 weeks and HBV viral load must be less than 100 IU/mL prior to first dose of study drug. Subjects on active HBV therapy with viral loads under 100 IU/ml should stay on the same therapy throughout study treatment.
Subjects who are anti-HBc (+), negative for HBsAg, negative for anti-HBs, and have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis.
HCV-HCC: active or resolved HCV infection as evidenced by detectable HCV RNA or antibody. Patients who have failed HCV therapy as evidenced by detectable HCV RNA will be eligible. Subjects with chronic infection by HCV who are treated (successfully or treatment failure) or untreated are allowed on study. In addition, subjects with successful HCV treatment are allowed as long as there are ≥4 weeks between completion of HCV therapy and start of study drug.
Successful HCV treatment definition: SVR12.
- Prior therapy is allowed provided the following are met: at least 4 weeks since prior locoregional therapy including surgical resection, chemoembolization, radiotherapy, or ablation. Provided target lesion has increased in size by 25% or more or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible 1 week after treatment as long as the target lesion is not the treated lesion.
iii) Subjects with psoriasis requiring systemic therapy must be excluded from enrollment
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT03519997|
|Other Study ID Numbers ICMJE||STU 102017-015|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||
|Responsible Party||University of Texas Southwestern Medical Center|
|Study Sponsor ICMJE||University of Texas Southwestern Medical Center|
|Collaborators ICMJE||Merck Sharp & Dohme Corp.|
|PRS Account||University of Texas Southwestern Medical Center|
|Verification Date||September 2019|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP