UAB 0142

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

1. 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.



2. To define the dose-limiting and non dose-limiting toxicities of DX-8951f in this patient population.



3. To correlate and study the utility of the erythromycin breath test and the caffeine urinary test as surrogate markers of DX-8951f elimination.



4. To determine the effects of hepatic dysfunction on the plasma pharmacokinetics and pharmacodynamics of DX-8951f.



5. 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:

1. All patients must have histologically or cytologically confirmed advanced solid tumor malignancy.



2. Patients refractory to standard therapy or for which no standard therapy exists.



3. Men and women of any racial and ethnic group who are 18 years of age or older will be included.



4. ECOG performance status 0-2.



5. Expected survival of at least 12 weeks.



6. 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


7. 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.



8. Fully recovered from any previous surgery (at least four weeks since major surgery).



9. Must have recovered from prior radiation therapy (at least four weeks since radiation).



10. Must have recovered from prior chemotherapy (at least four weeks since chemotherapy, greater than 6 weeks since the administration of mitomycin or nitrosourea).



11. Participants (male or female) must agree to practice approved methods of birth control (if applicable).



12. 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:

1. Prior cancer chemotherapy with DX-8951f.



2. Concurrent cancer chemotherapy, radotherapy, or surgery.



3. 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.



4. 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.



5. Presence of symptomatic/active brain metastasis, a CT or MRI scan of the brain should be performed prior to entry on study.



6. Overt psychosis or mental instability or otherwise incompetent to give informed consent.



7. 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.