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A Phase I Pharmacokinetic Trial of LY231514 Administered Intravenously Every 3 Weeks in Advanced Cancer Patients With Varying Degrees of Renal Function

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Pharmacokinetic Trial of LY231514 Administered Intravenously Every 3 Weeks in Advanced Cancer Patients With Varying Degrees of Renal Function

OBJECTIVES: I. Determine the toxic effects and maximum tolerated dose (MTD) of LY231514 in
patients with metastatic or locally advanced solid tumors and varying degrees of renal
function. II. Determine the recommended dose for LY231514 in this patient population. III.
Examine the effects of renal dysfunction on the pharmacokinetics of LY231514 in this patient
population. IV. Examine the relationship between impaired renal function, drug exposure, and
drug effects in these patients. V. Gather data for development of a LY231514 dosing nomogram
based on renal function. VI. Collect preliminary data regarding antitumor effects of
LY231514 in this patient population.

OUTLINE: This is an open label, dose escalation study. Patients are stratified according to
renal function. Group 1 consists of patients with normal renal function, and groups 2, 3,
and 4 consist of patients with mild, moderate, and severe renal impairment. All patients
receive LY231514 IV over 10 minutes every 3 weeks. Treatment continues in the absence of
disease progression or unacceptable toxicity. Cohorts of 3-6 patients are treated with
escalating doses of LY231514 within each treatment group. If dose limiting toxicity (DLT) is
observed in 1 of 3 patients at a given dose level, then 3 additional patients are studied.
The maximum tolerated dose is defined as the dose level at which less than 2 of 6 patients
experience DLT. Patients are followed until death.

PROJECTED ACCRUAL: Up to 50 patients will be accrued for this study.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed metastatic or locally
advanced solid tumors that have failed standard therapy or for which no standard therapy
exists Measurable or evaluable disease No active, symptomatic brain metastases No
leukemia, lymphoma, or multiple myeloma No significant pleural or peritoneal effusions

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At
least 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count
at least 100,000/mm3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin no greater than 1.5
times upper limit of normal (ULN) AST and ALT no greater than 3 times ULN (no greater than
5 times ULN if due to liver disease) Albumin at least 2.0 g/dL Renal: Not specified Other:
Not pregnant or nursing Negative pregnancy test Fertile patients must use effective
contraception during and for 3 months after study No active infection or serious
concurrent systemic disorders No second primary malignancy in the past 5 years except
carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin No
body surface area greater than 3 m2

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy No concurrent
routine use of filgrastim (G-CSF) or sargramostim (GM-CSF) Chemotherapy: At least 4 weeks
since prior chemotherapy (6 weeks since nitrosoureas or mitomycin) and recovered No other
concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy (except
contraceptives and corticosteroids) Radiotherapy: At least 4 weeks since prior
radiotherapy (including wide field pelvic radiation) No concurrent radiotherapy Surgery:
Not specified Other: At least 4 weeks since prior investigational agents Concurrent
warfarin and heparin allowed No aspirin and other nonsteroidal antiinflammatory 2 days
before, the day of, and 2 days after LY231514 administration (5 days for long-acting
agents) No concurrent nonsteroidal antiinflammatory drugs or salicylates with a long
half-life e.g., naproxen, piroxicam, diflunisal, or nabumetone) No other concurrent
experimental medications No concurrent dialysis

Type of Study:


Study Design:

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

Principal Investigator

Eric K. Rowinsky, MD

Investigator Role:

Study Chair

Investigator Affiliation:

San Antonio Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

April 1998

Completion Date:

June 2002

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific



San Antonio Cancer Institute San Antonio, Texas  78229-3264