Phase I Pharmacokinetic and Pharmacodynamic Trial of Irinotecan in Combination With Tomudex in Patients With Refractory Solid Malignancies
irinotecan hydrochloride
+ raltitrexed
Treatment Study
Summary
Study start date: December 1, 1997
Actual date on which the first participant was enrolled.OBJECTIVES: I. Determine the maximum tolerated dose of irinotecan in combination with raltitrexed in patients with refractory solid tumors. II. Describe and quantify the toxic effects of this combination treatment regimen in a minimally pretreated patient population. III. Determine the pharmacokinetics of this combination treatment regimen. IV. Document any antitumor activity of this combination treatment regimen in this patient population. OUTLINE: This is a dose escalation study of irinotecan and raltitrexed. Patients receive irinotecan IV over 90 minutes on days 1 and 8 followed by raltitrexed IV over 15 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of irinotecan and raltitrexed until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Additional cohorts receive raltitrexed on day 2 rather than day 1 near the final dose levels of the combination drugs. PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study within 1 year.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.39 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Criteria
DISEASE CHARACTERISTICS: Histologically proven malignant solid tumor that has failed prior conventional chemotherapy or for which no established therapy exists Recurrent or metastatic gastrointestinal adenocarcinoma with no prior therapy eligible No evidence of CNS metastases (brain or leptomeningeal disease) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: At least 12 weeks Hematopoietic: WBC at least 3,500/mm3 Neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.8 mg/dL SGOT and SGPT less than 3 times upper limit of normal (ULN) Alkaline phosphatase less than 3 times ULN (5 times ULN for metastatic disease) Renal: Creatinine no greater than 1.8 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No congestive heart failure Other: No uncontrolled diabetes Not pregnant or nursing Negative pregnancy test No other serious medical illness (e.g. clinically active infectious process) No psychiatric illness precluding study No ascites or pleural effusion PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior chemotherapy and recovered No more than 1 prior adjuvant chemotherapy regimen No more than 1 prior chemotherapy regimen for recurrent or metastatic disease No prior irinotecan or raltitrexed At least 8 weeks since prior nitrosourea or mitomycin and recovered Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy and recovered Prior radiotherapy limited to no greater than 25% of bone marrow Surgery: Not specified
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location