Overview

RDEA119 and Sorafenib Combination Dose Escalation Study

Status:
Completed
Trial end date:
2012-04-01
Target enrollment:
0
Participant gender:
All
Summary
Phase 1/2 dose escalation study to investigate the combination of RDEA119 and sorafenib in advanced cancer patients.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Bayer
Treatments:
Niacinamide
Sorafenib
Criteria
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.