Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

All Drugs and Chemicals

Mitogens

For purposes of data recording, the treatment period will be divided into 3-week cycles. Patients will continue on treatment until at least one of the following occurs (main criteria): Death Unacceptable toxicity Subject withdraws consent Substantial non-compliance with the protocol Treating physician determines discontinuation of treatment is in the subject's best interest. Radiological progression as determined by RECIST (Version 1.1) or mRECIST criteria or clinical progression (e.g. Eastern Cooperative Oncology group performance status - ECOG PS ≥3) patients may continue to receive study treatment if identified as having continued clinical benefit as judged by the treating physician.

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

Refametinib (BAY86-9766)

Bayer Study Director

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.

Refametinib(BAY86-9766) in RAS Mutant Hepatocellular Carcinoma (HCC)

A Prospective, Single-arm, Multicenter, Uncontrolled, Open-label Phase II Trial of Refametinib (BAY86-9766) in Patients With RAS Mutant Hepatocellular Carcinoma (HCC)

Bayer

Antineoplastic Agents

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

In Cycle 1 reduced sorafenib dose (600 mg daily; 200 mg in the morning + 400 mg in the evening) is administered, which is escalated to the standard dose in Cycle 2, if no Hand-foot skin reaction (HFSR), fatigue, or gastrointestinal (GI) toxicities of grade 2 or higher occur. For the purposes of data recording, the treatment period will be divided into 3-week cycles. Patients will continue on treatment until at least one of the following occurs (main criteria): Progressive Disease (PD) {PD as defined by mRECIST criteria or clinical progression \[e.g. Eastern Cooperative Oncology Group performance status (ECOG PS) of ≥3\], treatment may be continued past radiological progression, provided the patient derives clinical benefit as judged by the treating physician.}, Death, Unacceptable toxicity, Subject withdraws consent, Treating physician determines discontinuation of treatment is in the subject's best interest, Substantial non-compliance with the protocol

Patients will receive refametinib 50 mg (2x20 mg + 1x10mg capsules or 50 mg tablets) bid

Patients will receive sorafenib 400 mg (2 x 200 mg tablets) bid.

Sorafenib (BAY43-9006)

This is a study to investigate the potential clinical benefit of refametinib when given in combination with sorafenib as first line treatment 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 partial response according to an objective criteria to evaluate tumor size based on contrast enhancement \[modified response evaluation criteria in solid tumors (mRECIST)\] assessed by external independent radiologists.

Refametenib 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 in combination with sorafenib 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 in combination with sorafenib improves the response rate in this patient population compared to historical results observed with the sorafenib only.

Refametinib in Combination With Sorafenib in RAS Mutant Hepatocellular Carcinoma (HCC)

A Prospective, Single-arm, Multicenter, Uncontrolled, Open-label Phase II Trial of Refametinib (BAY86-9766) in Combination With Sorafenib as First Line Treatment in Patients With RAS Mutant Hepatocellular Carcinoma (HCC)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Refametinib(BAY86-9766) in RAS Mutant Hepatocellular Carcinoma (HCC)	NCT01915589	Carcinoma, Hepa...	Refametinib (BA...	18 Years -	Bayer
Refametinib in Combination With Sorafenib in RAS Mutant Hepatocellular Carcinoma (HCC)	NCT01915602	Carcinoma, Hepa...	Refametinib (BA... Sorafenib (BAY4...	18 Years -	Bayer
Refametinib(BAY86-9766) in RAS Mutant Hepatocellular Carcinoma (HCC)	NCT01915589	Carcinoma, Hepa...	Refametinib (BA...	18 Years -	Bayer

Spots Global Cancer Trial Database for objective tumor response rate (orr)