A
Phase I Study of DX-8951f (Exatecan Mesylate for Injection)
in Patients With Liver Dysfunction (Sponsor Protocol 8951A-PRT025)
SPONSOR:
Daiichi Pharmaceutical Corporation
PRINCIPAL
INVESTIGATOR: Wasif Saif, M.D.
OBJECTIVES
- To determine
the maximum tolerated dose of DX-8951f when given daily
for 5 consectuive days repeated every 3 weeks to patients
with liver dysfunction.
- To define
the dose-limiting and non dose-limiting toxicities of
DX-8951f in this patient population.
- To correlate
and study the utility of the erythromycin breath test
and the caffeine urinary test as surrogate markers of
DX-8951f elimination.
- To determine
the effects of hepatic dysfunction on the plasma pharmacokinetics
and pharmacodynamics of DX-8951f.
- To establish
a model for DX-8951f dosing in patients with liver dysfunction.
PATIENT
SELECTION CRITERIA
Inclusion
Criteria
At the time of
screening, all patients must meet the following criteria
for inclusion into the study:
- All patients
must have histologically or cytologically confirmed advanced
solid tumor malignancy.
- Patients refractory
to standard therapy or for which no standard therapy exists.
- Men and women
of any racial and ethnic group who are 18 years of age
or older will be included.
- ECOG performance
status 0-2.
- Expected survival
of at least 12 weeks.
- Must qualify
based on liver function parameters as defined by:
- Group
A: Normal Control: T. bilirubin <
ULN; AST < 2.5 x ULN
- Group
B: Mild Dysfunction: T. bilirubin <
ULN; AST > 2.5 x ULN
- Group
C: Mod. Dysfunction: T. bilirubin >
ULN but < 3.0 x ULN; any AST
- Group
D: Severe Dysfunction: T. bilirubin >
3.0 x ULN; any AST
- Adequate renal
and bone marrow function, defined as: serum creatinine
< 1.5 mg/dl; ANC > 1.5 x 103/mm3;
platelet count > 100 x 103/mm3,
hemoglobin > 9.0 gm/dl. All qualifying laboratory
parameters must be determined within two weeks prior to
first treatment.
- Fully recovered
from any previous surgery (at least four weeks since major
surgery).
- Must have
recovered from prior radiation therapy (at least four
weeks since radiation).
- Must have
recovered from prior chemotherapy (at least four weeks
since chemotherapy, greater than 6 weeks since the administration
of mitomycin or nitrosourea).
- Participants
(male or female) must agree to practice approved methods
of birth control (if applicable).
- Must provide
written informed consent.
Exclusion
Criteria
At the time of
screening, patients will be excluded from the study if any
of the following apply:
- Prior cancer
chemotherapy with DX-8951f.
- Concurrent
cancer chemotherapy, radotherapy, or surgery.
- Concurrent
serious infection or a life-threatening illness (unrelated
to tumor), e.g., active congestive heart failure, uncontrolled
angina, or myocardial infarction within 6 months prior
to study entry.
- Because of
the teratogenic potential of DX-8951f, women with the
potential to become pregnant, unless utilizing birth control,
or who are pregnant are excluded from the study. A negative
pregnancy test must be documented during the screening
period for women of childbearing potential. Breast feeding
women are excluded from this trial because of the potential
toxicity to the child. Men should avoid fathering children
during their participation in this study.
- Presence of
symptomatic/active brain metastasis, a CT or MRI scan
of the brain should be performed prior to entry on study.
- Overt psychosis
or mental instability or otherwise incompetent to give
informed consent.
- Administration
of any investigational drug (including analgesics or anti-emetics)
within 28 days prior to receipt of DX-8951f.
ADDITIONAL
INFORMATION
For further information,
contact Linda Pleasant, RN, BSN, OCN at (205) 934-9236 or
page through the UAB Paging Operator at (205) 934-3411,
Pager #6659.
