A Phase I Study of GTI-2040 in Combination With Oxaliplatin and Capecitabine in Patients With Advanced Metastatic Solid Tumors
GTI-2040
+ oxaliplatin
+ capecitabine
Maladies du côlon+13
+ Néoplasmes du côlon
+ Maladies du système digestif
Étude thérapeutique
Résumé
Date de début de l'étude : 1 mai 2004
Date à laquelle le premier participant a commencé l'étude.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.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.20 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.À partir de 18 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
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
Plan de l'étude
Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.Un seul groupe d'intervention est désigné dans cette étude
Cette étude ne comporte pas de groupe placebo.
Groupes de traitement
Groupe I
ExpérimentalObjectifs de l'étude
Objectifs principaux
Objectifs secondaires
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 1 site