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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01915589
Other study ID # 16553
Secondary ID 2013-000311-25
Status Completed
Phase Phase 2
First received
Last updated
Start date September 16, 2013
Est. completion date October 8, 2014

Study information

Verified date April 2021
Source Bayer
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a study to investigate the potential clinical benefit of refametinib in patients with unresectable or metastatic HCC carrying a RAS mutation. The study will be conducted in 2 stages. Approximately 95 patients (15 at Stage 1/ 80 at Stage 2) will be accrued to this study to receive treatment. Stage 2 of the trial will only be conducted if at least 5 out of 15 patients at Stage 1 show at least confirmed partial response (PR) according to modified response evaluation criteria in solid tumors (mRECIST) assessed by central image review. Refametinib is an oral (i.e. taken by mouth) protein kinase inhibitor. A kinase inhibitor targets certain key proteins that are essential for the survival of the cancer cell. By specifically targeting these proteins, refametinib may stop cancer growth. The growth of the tumor may be decreased by preventing these specific proteins from functioning. The primary endpoint (the most meaningful result to be tracked) of this study is based on the rate of response, i.e. the disease getting smaller. The aim is to show that the therapy with refametinib improves the response rate in this RAS mutation patient population.


Recruitment information / eligibility

Status Completed
Enrollment 16
Est. completion date October 8, 2014
Est. primary completion date October 8, 2014
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: Eligibility criteria for RAS mutation testing - Unresectable or metastatic HCC, confirmed either by histology or clinically according to the American Association for the Study of Liver Disease (AASLD) criteria for cirrhotic patients. For non-cirrhotic patients, histological confirmation is mandatory. - Male or female =18 years of age. - Eastern Cooperative Oncology Group (ECOG) performance state 0 or 1. - Life expectancy of at least 12 weeks. - No prior use of targeted agents, experimental therapy or systemic anti-cancer treatment for HCC (except sorafenib) - No previous treatment with refametinib(BAY86-9766). Criteria for study treatment eligibility - Patient must harbor GTPase Kirsten rat sarcoma viral oncogene homolog (KRAS) or Neuroblastoma RAS viral oncogene homolog (NRAS) mutation based on Beads, emulsions, amplification, and magnetic technology, sensitive mutation detection (BEAMing) plasma test. - Patients must have at least one uni-dimensional measurable lesion by Computed tomography (CT) or Magnetic resonance (MR) according to RECIST 1.1 and mRECIST which is either naïve (not previously treated by local therapy such as surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) or previously treated and has progressed until baseline (both measureable lesion and/or progressed lesion have to be confirmed by central image review of baseline and progression scan). - ECOG performance status of 0 or 1. - Liver function status of Child-Pugh Class A. - Adequate bone morrow, liver, and renal function - Patient has within normal range cardiac function confirmed by the enrolling clinical institute as measured by echocardiogram or multiple gated acquisition (MUGA) scan. - Patients who are therapeutically anti-coagulated with an agent such as warfarin or heparin are allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until International normalized ratio (INR) is stable (within Child Pugh class A threshold) based on a measurement at pre-dose, as defined by the local standard of care. Exclusion Criteria: - Any Cancer curatively treated < 3 years prior to study entry, except cervical carcinoma in situ (CIS), treated basal cell carcinoma, and superficial bladder tumors [Staging: noninvasive papillary tumor (Ta), CIS carcinoma (Tis) and tumor invades lamina propria (T1)] - Subjects who are eligible for surgery, liver transplantation, ablation or transarterial chemoembolization for HCC. - History of cardiac disease - Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg or diastolic blood pressure > 90 mmHg despite optimal medical management). - Ongoing infection > Grade 2 according to National Cancer Institute - Common Toxicity Criteria for Adverse Events version 4.03 (NCI-CTCAE version 4.03) Hepatitis B is allowed if no active replication (defined as abnormal Alanine aminotransferase [ALT] >2x Upper limit normal [ULN] associated with Hepatitis B virus [HBV] DNA >20,000 IU/mL) is present. Hepatitis C is allowed if no antiviral treatment is required. - Known history of, or symptomatic metastatic brain or meningeal tumors (head CT or MR at Screening to confirm the absence of central nervous system [CNS] disease if patient had symptoms suggestive or consistent with CNS disease). - History of interstitial lung disease (ILD). - History of hepatic encephalopathy. - History of organ allograft, cornea transplantation will be allowed. - History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR). - Visible retinal pathology as assessed by ophthalmologic exam that was considered a risk factor for RVO or CSR.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Refametinib (BAY86-9766)
All patients who meet the entry criteria will receive refametinib 50 mg (2x20 mg + 1x10 mg capsules or 50 mg tablet) bid.

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Czechia,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Spain,  Switzerland,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Objective tumor response according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) assessed by central radiological review Approximately 36 months
Secondary Objective tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by central radiological review Approximately 36 months
Secondary Objective tumor response according to RECIST 1.1 and mRECIST assessed by investigators Approximately 36 months
Secondary Disease control (central and investigator's assessment) Approximately 36 months
Secondary Overall survival Approximately 36 months
Secondary Time to radiographic tumor progression (central and investigator's assessment) Approximately 36 months
Secondary Duration of response (central and investigator's assessment) Approximately 36 months
Secondary Time to objective response (central and investigator's assessment) Approximately 36 months
Secondary Change in tumor size (central and investigator's assessment) Approximately 36 months
Secondary Best overall response (central and investigator's assessment) Approximately 36 months
Secondary Progression-free survival (central and investigator's assessment) Approximately 36 months
Secondary Number of participants with adverse events as a measure of safety and tolerability Approximately 36 months
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