RDEA119 and Sorafenib Combination Dose Escalation Study

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. Read our disclaimer for details. Identifier: NCT00785226
Recruitment Status : Completed
First Posted : November 5, 2008
Last Update Posted : October 17, 2016
Information provided by (Responsible Party):

Brief Summary:
Phase 1/2 dose escalation study to investigate the combination of RDEA119 and sorafenib in advanced cancer patients.

Condition or disease Intervention/treatment Phase
Advanced Cancer Drug: RDEA119 Drug: Sorafenib Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of the Combination of RDEA119 and Sorafenib in Patients With Advanced Cancer
Study Start Date : November 2008
Actual Primary Completion Date : April 2012
Actual Study Completion Date : April 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: RDEA119 with Sorafenib
Total daily doses of RDEA119 from 10 mg/day to 100 mg/day and sorafenib from 400 mg/day to 800 mg/day.
Drug: RDEA119
Total daily doses of RDEA119 from 10 mg/day to 100 mg/day
Other Names:
  • Refametinib;
  • RDEA119;
  • BAY 86-9766

Drug: Sorafenib
Total daily doses of sorafenib from 400 mg/day to 800 mg/day.

Primary Outcome Measures :
  1. To evaluate the safety and tolerability of escalating continuous oral dosing of RDEA119 in combination with sorafenib in advanced cancer patients. [ Time Frame: 28 Days ]

Secondary Outcome Measures :
  1. Determine PK and PD of drugs in combination, describe responses, correlate toxicity and response profiles to select biomarkers, and evaluate the safety and tolerability of the MTD of this combination in select tumors in Phase 2 portion. [ Time Frame: 28 days ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Inclusion Criteria: - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. - Histological or cytological confirmed diagnosis of a solid tumor. In the dose escalation phase, the tumor must be unresectable and locally advanced, or metastatic, and either no proven effective therapy exists or the patient cannot tolerate such therapy. Patients enrolled in the expanded MTD phase of the study must have either HCC or another select tumor type (melanoma, head and neck, colorectal, breast, or thyroid). For HCC patients in the expanded MTD phase: - Documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable. Histological confirmation is mandatory for patients without cirrhosis. - Patients with cirrhosis may have a clinical diagnosis of HCC by the American Association for the Study of Liver Diseases (AASLD) criteria.-cytotoxic chemotherapy; a targeted agent, including sorafenib; or other experimental treatment) are eligible. For non-HCC patients in the expanded MTD phase: - The tumor must be amenable to biopsy and the patient must be willing to consent to biopsy. - Life expectancy of > 3 months. - Evidence of measurable disease by RECIST criteria on computer assisted tomography (CT) or magnetic resonance imaging (MRI). - Normal/adequate swallowing capability, functional small bowel intact, and no malabsorption problems (in order to maximally quantify PK absorption characteristics). - Amylase and lipase < or equal to 2 x upper limit of normal (ULN). - Hemoglobin > or equal to 8.5 g/L. - ANC > or equal to 1,500/mm3. - Platelet count > or equal to 75,000/mm3. - Total bilirubin < or equal to 1.5 x ULN (For patients with HCC, refer to criterion number 14). - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < or equal to 2.5 x ULN (< or equal to 5 x ULN for patients with liver involvement). - PT-INR/PTT < or equal to 1.5 x ULN (Patients who are being prophylactically anti-coagulated with an agent such as coumadin or low molecular weight heparin (LMWH) or therapeutically anti-coagulated with LMWH will be allowed to participate provided that they meet these criteria; in addition, these patients must be monitored at appropriate intervals throughout the study). - Patients with HCC should have a Child-Pugh score of 5-6 (Class A). - Creatinine < or equal to 1.5 x ULN. - Patients must not be pregnant or breast-feeding, as chemotherapy is thought to present substantial risk to the fetus/infant. Men and women of reproductive potential may not participate in this study unless they have agreed to use an effective contraceptive method while on study. - No severe or uncontrolled intercurrent illness that in the opinion of the investigator would adversely impact the safety or efficacy of the treatment. - Ability to understand and willingness to sign a written informed consent form. - Patients must be within normal range cardiac function as measured by echocardiogram or multiple-gated acquisition (MUGA) scan. Exclusion Criteria: - Previous treatment with sorafenib that required a dose reduction due to toxicity. - Previous treatment with RDEA119. - Patients who have had cytotoxic chemotherapy or radiotherapy within 4 weeks prior to entering the study, those who have not recovered from adverse events due to agents administered more than 4 weeks earlier, those who have concurrent use of cytotoxic chemotherapy not indicated in the study protocol, or those with use of any other investigational agents < 4 weeks from the first dose of the study drug. - Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in the study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry. - Swallowing dysfunction and/or malabsorption syndrome that would impair sorafenib and RDEA119 treatment. - Cardiac disease: Congestive heart failure > New York Heart Association (NYHA) Class 2. Patients must not have unstable angina or new onset angina (within the last 3 months) or myocardial infarction (MI) within the past 6 months. - Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. - Uncontrolled hypertension - Known human immunodeficiency virus (HIV) infection. - Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months. - Evidence or history of bleeding diathesis or coagulopathy. - Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug. - The use of inhibitors or inducers of CYP3A4 and CYP2C19 enzymes, as well as the concurrent treatment with any of the agents listed in Section 3.7 of the protocol. These and other medications that are inhibitors and inducers of CYP3A4 and CYP2C19 should be discussed with the sponsor. - Patients with known hypersensitivity to any of the drugs or components given in this protocol. - Patients with abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess, or small bowel resection, any of which is within 6 months of study entry. - Patients with abdominal radiation resulting in chronic diarrhea. - Patients with documented central nervous system (CNS) metastasis who are not off steroids and other CNS therapies. - Evidence of uncontrolled active infections except HCV and HBV. - Other serious medical or psychiatric illness that would not permit the patient to be managed according to the protocol.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00785226

United States, California
USC/Norris Comprehensive Cancer Center and LAC/USC Medical Center
Los Angeles, California, United States, 90033
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169
United States, New York
New York Oncology Hematology, PC
Albany, New York, United States, 12206
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
James P. Wilmot Cancer Center
Rochester, New York, United States, 14642
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Greenville Hospital System University Medical Center, (ITOR)
Greenville, South Carolina, United States, 29605
United States, Texas
Texas Oncology - Baylor Charles A. Simmons Cancer Center
Dallas, Texas, United States, 75246
Texas Oncology-Tyler
Tyler, Texas, United States, 75702
Canada, Ontario
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2N2
Sponsors and Collaborators
Study Director: Bayer Study Director Bayer

Additional Information:
Publications of Results:
Responsible Party: Bayer Identifier: NCT00785226     History of Changes
Other Study ID Numbers: 15507
RDEA119-103 ( Other Identifier: Ardea )
First Posted: November 5, 2008    Key Record Dates
Last Update Posted: October 17, 2016
Last Verified: October 2016

Additional relevant MeSH terms:
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs