Brief Title
Sorafenib in Treating Patients With Metastatic or Unresectable Solid Tumors, Multiple Myeloma, or Non-Hodgkin's Lymphoma With or Without Impaired Liver or Kidney Function
Official Title
Pharmacokinetic and Phase I Study of Sorafenib (BAY 43-9006, NSC 724772, IND 69896) for Solid Tumors and Hematologic Malignancies in Patients With Hepatic or Renal Dysfunction
Brief Summary
This phase I trial is studying the side effects and best dose of sorafenib in treating
patients with metastatic or unresectable solid tumors, multiple myeloma, or non-Hodgkin's
lymphoma with or without impaired liver or kidney function. Sorafenib may stop the growth of
cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood
flow to the cancer. Sorafenib may have different effects in patients who have changes in
their liver or kidney function
Detailed Description
PRIMARY OBJECTIVES:
I. To characterize the pharmacokinetics of BAY 43-9006 in patients with hepatic or renal
dysfunction (part 1 of the study).
II. To determine a tolerable starting dose of BAY 43-9006 in patients with varying degrees of
hepatic or renal dysfunction (part 2 of the study).
OUTLINE: This is a dose-escalation, multicenter study. Patients are assigned to 1 of 9
treatment cohorts according to hepatic or renal function.
Patients receive oral sorafenib once on day 1 and then once daily, twice daily, or every
other day beginning on day 8 and continuing for 3 months. Patients are re-evaluated at 3
months. Patients with responding disease may continue study treatment in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-6 patients (per treatment cohort) receive escalating doses of sorafenib until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that
at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are
treated at the MTD.
PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Relationship between the pharmacokinetics and measures of renal dysfunction categorized by creatinine clearance as estimated by the Cockcroft and Gault formula (Part 1)
Condition
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Intervention
sorafenib tosylate
Study Arms / Comparison Groups
Treatment (sorafenib tosylate)
Description: Patients receive oral sorafenib once on day 1 and then once daily, twice daily, or every other day beginning on day 8 and continuing for 3 months. Patients are re-evaluated at 3 months. Patients with responding disease may continue study treatment in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients (per treatment cohort) receive escalating doses of sorafenib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
150
Start Date
October 2004
Primary Completion Date
May 2007
Eligibility Criteria
Inclusion Criteria:
- Patients must have cytologically or histologically confirmed tumors that are
metastatic or unresectable and for which standard curative or palliative measures do
not exist or are no longer effective; Patients with solid tumors, multiple myeloma, or
non-Hodgkin's lymphoma are eligible
- Lesions that can be accurately measured in at least one dimension (longest diameter to
be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
- All other lesions, including small lesions (longest diameter < 20 mm with conventional
techniques or < 10 mm with spiral CT scan) and truly nonmeasurable lesions; Lesions
that are considered non-measurable include the following:
- Bone lesions
- Ascites
- Pleural/pericardial effusion
- Lymphangitis cutis/pulmonis
- Abdominal masses that are not confirmed and followed by imaging techniques
- Cystic lesions
- ≥ 4 weeks since major surgery
- ≥ 4 weeks since completion of radiation or chemotherapy except for ≥ 6 weeks for
nitrosoureas, L-PAM or mitomycin-C
- ECOG Performance Status of 0-2
- Non-pregnant and non-nursing because the effects of BAY 43-9006 on the fetus/infant
are unknown; in addition, women of child-bearing potential and men must agree to use
an appropriate method of birth control throughout their participation in this study;
appropriate methods of birth control include abstinence, oral contraceptives,
implantable hormonal contraceptives (Norplant), or double barrier methods (diaphragm
plus condom)
- No patients with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social
situations that would limit compliance with study requirements
- No concomitant medications known to cause hepatic or renal toxicity, including
anti-seizure medications, non-steroidal anti-inflammatory agents, and steroids
- No gastrointestinal tract disease resulting in an inability to take oral medication or
a requirement for IV alimentation, prior surgical procedures affecting absorption, or
active peptic ulcer disease
- No HIV-positive patients receiving combination anti-retroviral therapy because of
possible pharmacokinetic interactions with BAY 43-9006; however, patients who are HIV+
but without AIDS defining diagnosis and not on combination anti-retroviral therapy are
eligible
- No patients with evidence of biliary or renal obstruction; patients should be observed
for at least one week after treatment (i.e. stents or drains) for biliary or renal
obstruction to ensure their organ dysfunction has stabilized before registration to
this protocol
- No current treatment with other investigational agents
- No evidence of bleeding diathesis
- No patients on therapeutic anticoagulation; prophylactic anticoagulation (i.e., low
dose warfarin) of venous or arterial access devices is allowed provided that the
requirements for PT, INR or PTT is met
- No treatment with cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin,
carbamazepine or Phenobarbital), rifampin or St. John's wort
- Patients with brain metastases are eligible if they meet all of the following
criteria:
- Asymptomatic
- Radiographically stable disease for at least 2 months
- Previously received treatment for the brain metastases
- Not currently receiving steroid therapy or enzyme-inducing anticonvulsants (e.g.
phenytoin, phenobarbital, or carbamazepine)
- Granulocytes ≥ 1,500/μl
- Platelet count ≥ 75,000/μl
- Normal or abnormal organ function
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Antonius Miller, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00118170
Organization ID
NCI-2012-03083
Secondary IDs
CALGB-60301
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Antonius Miller, Principal Investigator, Cancer and Leukemia Group B
Verification Date
January 2013