A Randomized Phase II Trial of Pre-Chemotherapy Leukine Vs. Leukine-Dexamethasone in Combination With Gemcitabine and 5-Fluorouracil (5-FU) in Patients With Metastatic Renal Cell Carcinoma (RCC)
1. Determine the response rates and overall survival in patients with metastatic renal
cell carcinoma (RCC) receiving pre-treatment with Leukine-dexamethasone vs Leukine
alone in combination with gemcitabine-5-FU.
2. Determine if pre-treatment with the combination of Leukine-dexamethasone is more
effective than pre-treatment with Leukine alone in reducing the hematopoietic and
non-hematopoietic toxicities of gemcitabine-5-FU in patients with metastatic RCC.
1. Determine the effects of the combination of Leukine-dexamethasone vs Leukine alone on
the number and function of peripheral blood dendritic cells, and cytokine levels when
given prior to gemcitabine-5-FU in patients with metastatic RCC.
2. Determine quality of life and toxicity of treatment in patients with metastatic RCC
receiving pre-treatment with Leukine-dexamethasone vs Leukine alone in combination with
3. Determine the dose intensity administered in both treatment groups.
- Overall study design: A randomized Phase II study in patients with metastatic RCC
Patients will receive chemotherapy with gemcitabine-5-FU. Patients will receive prior
to each chemotherapy the combination of Leukine alone (Cohort 1) or
Leukine-dexamethasone (Cohort 2).
- Patient eligibility: a) chemotherapy naive patients with biopsy proven RCC, b) PS
(ECOG), 0, 1, or 2, c) measurable disease by RECIST criteria, d) previous immunotherapy
and anti-angiogenic therapy is allowed, e) adequate bone marrow, renal and hepatic
function as defined by AGC > 1500 and PLC > 100,000 mm3 and serum creatinine and
bilirubin < 1.5 mg/dl.
- Chemotherapy: Cohorts 1 and 2: Days 7 and 21: gemcitabine 1.0 g/m2 intravenously over
30 minutes; Days 7-8 and 21-22: Folinic acid 200 mg/ m2, then 5-FU 400 mg/ m2,
intravenously over 30 minutes followed by 5-FU 600 mg/ m2 intravenously over 24 hours.
- Study Drugs:
- Cohort 1, Leukine, 250 ug/m2 daily (8 am) subcutaneously days 1, 2, 3, 4, 5, and
15, 16, 17, 18, and 19;
- Cohort 2, Leukine, 250 ug/m2 daily (8 am) subcutaneously days 1, 2, 3, 4,5, and
15, 16, 17, 18, and 19 and dexamethasone 12 mg every 12 hours (8 am and 8 pm)
orally days 3, 4, 5,6, 7, 17, 18, 19, 20, and 21.
- Evaluations during this trial: Baseline: history and physical examination with vital
signs/weight, estimation of performance status (PS), CAT scans of chest, abdomen and
pelvis, EKG, CBC/differential, urinalysis, complete biochemistry profile (CMP) (12
component) and quality of life assessment. Prior to each course: interim history,
physical examination with vital signs/weight, grading of all toxicities, and estimation
of PS, CMP, and CBC/differential. Prior to course 3, 5, and thereafter (every other
course): CAT scans of chest, abdomen, and pelvis, tumor response and quality of life
assessment. Each week after initiation of study (ie day1, course 1): CBC/differential,
x 3 (Monday Wednesday and Friday). Biologic studies to include assessment of dendritic
cell number and function (20 ml blood), days 1 and 7 of course 1.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
% of subjects with CR or PR evaluated after course 2 then every other course using RECIST for both cohorts
John Rinehart, MD
University of Kentucky
United States: Food and Drug Administration