A Phase I Study of GTI-2040 in Combination With Oxaliplatin and Capecitabine in Patients With Advanced Metastatic Solid Tumors
GTI-2040
+ oxaliplatin
+ capecitabine
Colonic Diseases+13
+ Colonic Neoplasms
+ Digestive System Diseases
Treatment Study
Summary
Study start date: May 1, 2004
Actual date on which the first participant was enrolled.PRIMARY OBJECTIVES: I. To establish the maximum tolerated (MTD) of a 21 day cycle of capecitabine given orally twice daily for 14 days in combination with oxaliplatin given intravenously on day 1 and GTI-2040 given as a continuous infusion over 14 days in patients with advanced metastatic solid tumors. II. To describe the toxicities at each dose level studied. SECONDARY OBJECTIVES: I. To evaluate the pharmacokinetics of GTI-2040, capecitabine, and oxaliplatin when these are given in combination. II. To evaluate levels of ribonucleotide reductase -M2 subunit (RR-M2) mRNA levels using TaqMan RT-PCR in peripheral blood mononuclear cells and in tumor samples (when available). TRF support will be required and sought. III. To quantitate changes in dCTP levels in peripheral blood mononuclear cells during treatment as a surrogate marker of RR inhibition. TRF support will be required and sought. OUTLINE: This is a multicenter, dose-escalation study of capecitabine. Patients receive GTI-2040 IV continuously on days 1-14, oral capecitabine twice daily on days 2-15, and oxaliplatin IV over 2 hours on day 2 of the first course. In all subsequent courses, capecitabine is administered on days 1-14, oxaliplatin is administered on day 1, and GTI-2040 is administered as in course 1. Courses repeat every 21 days in the absence of disease progression and unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.20 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.Conditions
Pathology
Criteria
Inclusion Criteria: * Patients must have locally advanced or metastatic colorectal cancer that is not amenable to surgical treatment; selected patients with advanced disease in incurable cancers of other types may be considered * Patients must have histological or cytological proof of malignancy * Patients must have had at least one standard prior chemotherapy for locally advanced or metastatic disease with no prior oxaliplatin containing regimen; patients who relapse within 12 months of adjuvant therapy are eligible * Karnofsky performance status of \>= 60% * Absolute neutrophil count \> 1500/ul * Platelets \> 100,000/ul * Total bilirubin within institutional normal limits * AST (SGOT)/ALT (SGPT) within 2.5 x institutional normal limits * Alkaline phosphatase within 2.5x institutional normal limits * Creatinine within institutional normal limits or a calculated creatinine clearance \> 60 ml/min * Patients should have no greater than grade 1 neuropathy (CTCAE v3.0) * Ability to understand and the willingness to sign a written IRB approved consent document * Measurable disease not required * Previous chemotherapy must have been completed \> 21 days before treatment on this study (\> 6 weeks for mitomycin-c or nitrosoureas) * Life expectancy of at least 12 weeks Exclusion Criteria: * Active or chronic hepatitis B or C * HIV positive patients receiving antiviral therapy because of possible pharmacokinetic interactions * Uncontrolled intercurrent illnesses including but not limited to ongoing or active infections, symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia * Pregnant or nursing women are excluded due to the potential for teratogenic effects and for potential deleterious effects on the infant; woman of childbearing age and men must practice an effective form of contraception * Patients with known brain metastasis are excluded due their poor prognosis and due to possible neurologic sequelae that could confound the evaluation of the investigational treatment * Patients requiring anticoagulation are excluded as polyanions are known to inhibit clotting mechanisms and phosphorothioate oligonucleotide may act in a similar mechanism; patients receiving low dose prophylactic Coumadin (1 mg/day) may be included * Medical, social, of psychological factors that would interfere with consent and follow-up * Patients with a diagnosis of pulmonary fibrosis or a pulmonary interstitial process
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
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