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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


Phase 1
18 Years
N/A
Not Enrolling
Both
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Multiple Myeloma, Splenic Marginal Zone Lymphoma, Stage II Multiple Myeloma, Stage III Adult Burkitt Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Mixed Cell Lymphoma, Stage III Adult Diffuse Small Cleaved Cell Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Multiple Myeloma, Stage III Small Lymphocytic Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Small Lymphocytic Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific, Waldenström Macroglobulinemia

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Relationship between the pharmacokinetics and measures of renal dysfunction categorized by creatinine clearance as estimated by the Cockcroft and Gault formula (Part 1)

Outcome Description:

Explored using standard parametric and non-parametric methods for one- and two-way analysis of variance (ANOVA) layouts (the dysfunction factor (hepatic/renal) and the severity factor (mild, moderate, severe, very severe).

Outcome Time Frame:

Prior to and at 1, 2, 3, 4, 6, and 24 hours post-dose on day 1

Safety Issue:

No

Principal Investigator

Antonius Miller

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03083

NCT ID:

NCT00118170

Start Date:

October 2004

Completion Date:

Related Keywords:

  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Nodal Marginal Zone B-cell Lymphoma
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Multiple Myeloma
  • Splenic Marginal Zone Lymphoma
  • Stage II Multiple Myeloma
  • Stage III Adult Burkitt Lymphoma
  • Stage III Adult Diffuse Large Cell Lymphoma
  • Stage III Adult Diffuse Mixed Cell Lymphoma
  • Stage III Adult Diffuse Small Cleaved Cell Lymphoma
  • Stage III Adult Immunoblastic Large Cell Lymphoma
  • Stage III Adult Lymphoblastic Lymphoma
  • Stage III Grade 1 Follicular Lymphoma
  • Stage III Grade 2 Follicular Lymphoma
  • Stage III Grade 3 Follicular Lymphoma
  • Stage III Mantle Cell Lymphoma
  • Stage III Marginal Zone Lymphoma
  • Stage III Multiple Myeloma
  • Stage III Small Lymphocytic Lymphoma
  • Stage IV Adult Burkitt Lymphoma
  • Stage IV Adult Diffuse Large Cell Lymphoma
  • Stage IV Adult Diffuse Mixed Cell Lymphoma
  • Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
  • Stage IV Adult Immunoblastic Large Cell Lymphoma
  • Stage IV Adult Lymphoblastic Lymphoma
  • Stage IV Grade 1 Follicular Lymphoma
  • Stage IV Grade 2 Follicular Lymphoma
  • Stage IV Grade 3 Follicular Lymphoma
  • Stage IV Mantle Cell Lymphoma
  • Stage IV Marginal Zone Lymphoma
  • Stage IV Small Lymphocytic Lymphoma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Waldenström Macroglobulinemia
  • Burkitt Lymphoma
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Waldenstrom Macroglobulinemia
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Neoplasms
  • Lymphoma, Mantle-Cell

Name

Location

Cancer and Leukemia Group B (CALGB) Research BaseChicago, Illinois  60604-1104