An Open-Label Study of Regorafenib in Combination with Pembrolizumab in Patients with Advanced or Metastatic Hepatocellular Carcinoma (HCC) after PD-1/PD-L1 Immune Checkpoint Inhibitors

BAYER AG0 个研究点目标入组 119 人开始时间: 2020年10月8日最近更新: 2024年4月29日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: BAYER AG
入组人数: 119

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•- =18 years of age on the day of signing informed consent
•- Histological or cytological confirmation of HCC or non-invasive
•diagnosis of HCC as per AASLD criteria in cirrhotic participants
•- Unresectable advanced HCC eligible for systemic therapy
•- Participants must have progressed after only one prior line of systemic
•immunotherapy treatment with an anti-PD-1/PD-L1 mAb administered
•either as monotherapy or in combination with other checkpoint
•inhibitors or other therapies (for prior therapy in the cohorts in the pilot
•phase see Section 4.1). A wash out period of at least 28 days or 5 halflives,
•whichever is shorter, must be completed for eligibility in this trial.
•PD-1/PD-L1 treatment progression is defined by meeting all of the
•following criteria:
•a. Has received at least 2 doses of an approved anti-PD-1/PD-L1 mAb or
•received PD-1/PD-L1 treatment for 8 weeks, whichever is longer.
•b. Has demonstrated disease progression after PD-1/PD-L1 treatment as
•defined by RECIST 1.1 (see Appendix 5, Section 10.5.1). In the absence
•of rapid clinical progression, the initial evidence of RECIST 1.1 disease
•progression is to be confirmed using iRECIST (see Appendix 5, section
•10.5.3) by a second assessment no less than four weeks from the date of
•the first documented progressive disease.
•i. This determination is made by the investigator. Once progressive
•disease is confirmed, the initial date of RECIST 1.1 progressive disease
•documentation will be considered that date of disease progression.
•ii. In cases of unequivocal clinical or radiological progression, disease
•progression confirmation may not be required after documented
•discussion and approval by the sponsor.
•c. Progressive disease has been documented within 12 weeks from the
•last dose of anti-PD-1/PD-L1 mAb.
•- Participants who receive anti-PD-1 therapy as adjuvant treatment
•following complete resection of liver cancer and have disease recurrence
•(unresectable loco-regional disease or distant metastases) are eligible if
•they progressed while on active treatment or within 6 months of
•stopping anti-PD-1 therapy. This will be considered the first line of
•systemic therapy.
•For these participants, the following applies:
•1)a second assessment to confirm disease progression beyond
•recurrence is not required; and
•2)they must have received at least 2 prior doses of anti-PD-1/PD-L1
•- BCLC stage B or C
•- Liver function status should be Child-Pugh (CP) Class A within 7 days
•prior to the first dose of study intervention. CP status should be
•calculated based on clinical findings and laboratory results during the
•screening period.
•- ECOG PS status of 0 or 1 within 7 days prior to the first dose of study
•intervention.
•- At least one measurable lesion by CT scan or MRI according to RECIST
•1.1. Tumor lesions situated in a previously irradiated area, or in an area
•subjected to other loco-regional therapy, may be considered measurable
•if there has been demonstrated progression in the lesion.
•- Participants with controlled (treated) hepatitis B virus (HBV) infection
另有 8 项未显示

排除标准

•- Fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes.
•-Patients with disease that is suitable for local therapy administered with curative intent.
•-Patients who experienced any CTCAE = 3 or any other immune related toxicities that led to permanent discontinuation of treatment with immune checkpoint inhibitors in 1 L.
•-Persistent proteinuria of CTCAE Grade 3 or higher.
•-Diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study interventions.
•- Active autoimmune disease
•- History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
•- Any hemorrhage or bleeding event CTCAE Grade = 3 within 28 days prior to the start of study medication.
•- Patients with large esophageal varices at risk of bleeding that are not being treated with conventional medical intervention
•- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication.
•- Ongoing infection CTCAE Grade > 2 requiring systemic therapy.
•- Dual active HBV infection (HBsAg (+) and / or detectable HBV DNA) and HCV infection (anti-HCV Ab (+) and detectable HCV RNA) at study entry.
•- Uncontrolled hypertension (systolic blood pressure = 140 mmHg or
•diastolic pressure = 90 mmHg) on more than 2 separate measurements
•despite optimal medical management.
•- Unstable angina (angina symptoms at rest), new-onset angina (begun
•within the last 3 months).
•- Myocardial infarction less than 6 months before start of study
•intervention.
•- Pleural effusion or ascites that causes respiratory compromise (CTCAE
•Grade =2 dyspnea).
•- Patients with previous malignancies (except non-melanoma skin
•cancers, and the following in situ cancers: bladder, gastric, colon,
•cervical/dysplasia, melanoma, or breast) are excluded unless a complete
•remission was achieved at least 3 years prior to study entry
•- Known active central nervous system (CNS) metastases and/or
•carcinomatous meningitis. Participants with previously treated brain
•metastases may participate provided they are radiologically stable,
•- Significant acute gastrointestinal disorders with diarrhea as a major
•-Current evidence or suspicion of gastrointestinal perforation or fistula.
•- Prior monotherapy treatment with any tyrosine kinase inhibitor in 1L.
•- Prior treatment with regorafenib, in combination regimens with
•immune checkpoint inhibitors.
•- Transfusion of blood products within 7 days prior to signing informed
•consent, or administration of colony stimulating factors within 4 weeks
•prior to signing informed consent.
•- Previous assignment to treatment during this study.
•- Previous (at least a minimum of 28 days, or 5 half-lives of an
•investigational drug before the start of study treatment, whichever is
•shorter) or concomitant participation in another clinical study with investigational medicinal product(s).

研究者

发起方

BAYER AG

相似试验

已完成

2 期

Regorafenib Plus Pembrolizumab in Patients With Advanced or Spreading Liver Cancer Who Have Been Previously Treated With PD-1/PD-L1 Immune Checkpoint InhibitorsHepatocellular Carcinoma

JPRN-jRCT2031200435Tanigawa Takahiko119

进行中（未招募）

1 期

Pilot study of regorafenib plus pembrolizumab in patients who have been previously treated with PD-1/PD-L1 Immune Checkpoint Inhibitors and are suffering from liver cancer which may have spread to nearby tissue and is unlikely to be cured or controlled with treatmentA type of liver cancer which may have spread to nearby tissue and is unlikely to be cured or controlled with treatmentMedDRA version: 21.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864

EUCTR2020-003555-16-ESBAYER AG119

进行中（未招募）

1 期

EUCTR2020-003555-16-FRBAYER AG119

进行中（未招募）

1 期

EUCTR2020-003555-16-ITBAYER AG119

进行中（未招募）

1 期

Regorafenib given to patients with metastatic colorectal cancer (CRC) who have failed all available standard therapyColorectal neoplasms

EUCTR2011-005836-25-CZBayer HealthCare AG2,872