Clinical trial NCT00002904: Ecteinascidin 743 in Treating Adults With Advanced Solid Tumors
Official title: PHASE I CLINICAL AND PHARMACOKINETIC STUDY TO DETERMINE THE SAFETY OF ECTEINASCIDIN-743 (ET-743) ADMINISTERED AS A SINGLE INTRAVENOUS INFUSION OVER 60 MINUTES EVERY 21 DAYS IN PATIENTS WITH SOLID TUMORS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2004-09-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of ecteinascidin 743 in treating adults with advanced solid tumors.

Detailed description: OBJECTIVES: I. Estimate the maximum tolerated dose (MTD) of ecteinascidin-743 (ET-743) when administered as a single intravenous infusion every 21 days in adults with solid tumors not amenable to standard therapy. II. Describe the qualitative and quantitative toxic effects of ET-743, and study the predictability, duration, intensity, onset, reversibility, and dose-relationship of these toxic effects in these patients. III. Propose a safe dose for a phase II study based on the MTD determined on this study. IV. Assess the pharmacokinetics of ET-743 at different dose levels. V. Document any antitumor effects of ET-743 in these patients.

OUTLINE: This is a multicenter study. All patients receive ET-743 IV over 3 hours every 21 days for 4 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ET-743 until the maximum tolerated dose is determined. Patients are followed at 1 month, then every 3 months until disease progression.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study over 12 months.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically or cytologically confirmed solid tumor that is not amenable to standard therapy No evidence of brain involvement or leptomeningeal disease

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: ANC at least 2,000/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin less than 1.5 mg/dL Transaminases normal (no greater than 2.5 times normal if liver metastases) Alkaline phosphatase normal (no greater than 2.5 times normal if liver or bone metastases) No history of chronic liver disease, e.g., chronic active hepatitis, cirrhosis Renal: Creatinine no greater than 1.4 mg/dL Creatinine clearance at least 60 mL/min Other: No active bacterial infection (e.g., abscess) or with fistulae No grade 2 or worse neurotoxicity No concurrent medical condition that precludes treatment No history of alcoholism, drug addiction, or psychotic disorder Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Colony-stimulating factors allowed for specific indications At least 4 weeks since prior biologic therapy, immunotherapy, or growth factors Chemotherapy: No prior intensive chemotherapy with bone marrow or stem cell support At least 4 weeks since chemotherapy (6 weeks since nitrosoureas, mitomycin, or high-dose carboplatin) Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since radiotherapy Concomitant palliative local radiotherapy allowed for existing lesion Surgery: Recovered from prior surgery Other: No concurrent investigational drug Concurrent prophylactic antiemetics allowed after first therapy course

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna (Wien)
country: Austria
facility: Ludwig Boltzmann - Institute for Applied Cancer Research
city: Brussels (Bruxelles)
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev Hospital - University Hospital of Copenhagen
city: Bordeaux
country: France
facility: Institut Bergonie
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Georges-Francois Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: CHU de la Timone
city: Nantes-Saint Herblain
country: France
facility: CRLCC Nantes - Atlantique
city: Paris
country: France
facility: Institut Curie - Section Medicale
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Hopital Paul Brousse
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Halle Saale
country: Germany
facility: Martin Luther Universitaet
city: Hamburg
country: Germany
facility: Universitats-Krankenhaus Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Nuremberg (Nurnberg)
country: Germany
facility: Klinikum Nurnberg
city: Ioannina
country: Greece
facility: University of Ioannina
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Petah-Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - Aviano
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Naples (Napoli)
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
city: Rome
country: Italy
facility: San Raffaele Hospital
city: Rome
country: Italy
facility: Istituti Fisioterapici Ospitalieri - Roma
city: Amsterdam
country: Netherlands
facility: Academisch Ziekenhuis der Vrije Universiteit
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoekhuis
city: Groningen
country: Netherlands
facility: Academisch Ziekenhuis Groningen
city: Nijmegen
country: Netherlands
facility: St. Radboud University Hospital
city: Rotterdam
country: Netherlands
facility: Rotterdam Cancer Institute
city: Oslo
country: Norway
facility: Norwegian Radium Hospital
city: Lisbon
country: Portugal
facility: Instituto Portugues de Oncologia de Francisco Gentil
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Basel
country: Switzerland
facility: University Hospital
city: Bellinzona
country: Switzerland
facility: Ospedale San Giovanni
city: Bern
country: Switzerland
facility: Inselspital, Bern
city: Genolier
country: Switzerland
facility: Clinique De Genolier
city: Saint Gallen
country: Switzerland
facility: Kantonsspital - Saint Gallen
city: London
country: United Kingdom
facility: Royal Marsden NHS Trust
state: England
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle General Hospital
state: England
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson Oncology Centre
state: Scotland
Study officials:
affiliation: University of Glasgow
name: Chris Twelves, MD, BMedSci, FRCP
role: STUDY_CHAIR
References: