Clinical trial NCT00496509: Phase I Efficacy On Vascular Permeability In Patients With Advanced Colorectal Cancer
Official title: A Phase I, Open-Label Study To Assess The Effect of ZD6474 (ZACTIMA) On Vascular Permeability In Patients With Advanced Colorectal Cancer and Liver Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Cancer
Keywords: ZD6474
Colorectal Cancer
Liver Metastases
Biomarkers
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2007-07-04
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Phase I, Open-Label Study To Assess The Effect of ZD6474 (ZACTIMA) On Vascular Permeability In Patients with Advanced Colorectal Cancer and Liver Metastases.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed metastatic colorectal adenocarcinoma (stage IV) with at least 1 measurable hepatic lesion of 20 mm or more on MRI and for whom no standard therapy is available.
* WHO Performance status 0 - 2.
* Life expectancy of at least 12 weeks

Exclusion Criteria:

* Brain metastases or spinal cord compression, unless treated at least 4 weeks before entry and stable without steroid treatment for 10 days or greater.
* Last dose of prior chemotherapy must be discontinued at least 4 weeks before the start of study treatment.
* Last dose of radiotherapy received within 4 weeks before the start of study treatment excluding palliative radiotherapy.
* Prior treatment with VEGFR TKIs
* Serum bilirubin . 1.5 x the upper limit of reference range.
* Serum creatinine \>1.5 x ULRR or Creatinine clearance (as determined by the Cockcroft - Gault method) less than or equal to 50 mL/min.
* ALT or AST \>5 x ULRR
* ALP \>5 x ULRR
* Evidence of severe or uncontrolled systemic disease or any concurrent conditions which in the investigators opinion make it undesirable for the patient to participate in the study or would jeopardize compliance with the protocol.
* Any unresolved toxicity greater than CTCAE Grade 2 for previous anti-cancer therapy.
* Significant cardiovascular event within 3 months before entry, or presence of cardiac disease that in the opinion of the investigator increases the risk of ventricular arrhythmia.
* History of arrhythmia which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled by medication is not excluded.
* Congenital long QT syndrome or 1st degree relative with sudden unexplained death under of 40 years of age.
* Presence of Left Bundle Branch Block.
* QTc with Bazett's correction unmeasurable or greater than or equal to 480 msec or greater of screening ECG.
* Potassium \<4.0 mmol/L despite supplementation, serum calcium (ionized or adjusted for albumin), or magnesium out of normal range despite supplementation.
* Women who are pregnant or breast feeding.
* Any concomitant medications that may cause QTc prolongation or induce or induce Torsades de Pointes or induce CTP3A4 function.
* Hypotension not controlled by medical therapy.
* Participation in a clinical study of any investigational pharmaceutical agent within 30 days prior to commencing study treatment.
* Major surgery within 4 weeks or incompletely healed surgical incision.
* Previous or current malignancies of other histologies within the last 5 years, with the exception of in situ carcinoma of the cervix and adequately treated basal cell or Squamous cell carcinoma of the skin.
* Any contraindications to MRI scans.
* Involvement in the planning or conduct of the study.
* Previous enrollment or randomization of treatment in the present study.

Primary outcomes:
measure: Assess by dynamic contrast-enhanced magnetic resonance imaging the effect of once daily dosing with ZD6474 on tumour perfusion and vascular permeability in patients with advanced colorectal cancer and liver metastases.
timeFrame: Up to 57 days.
Secondary outcomes:
measure: Assessment of appropriate Pharmacokinetic parameters
timeFrame: Predetermined timepoints after dose administration
measure: Determine the population PK of ZD6474 and assess the relationship between both free and total plasma PK and measures of Pharmacological activity
timeFrame: Predetermined timepoints after dose administration
measure: Assessment of the effectiveness of ZD6474 as measured by objective response rate and progression free survival based on RECIST.
timeFrame: Every 8 weeks during the study
Other outcomes:
Locations:
city: Freiberg
country: Germany
facility: Research Site
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mross K, Fasol U, Frost A, Benkelmann R, Kuhlmann J, Buchert M, Unger C, Blum H, Hennig J, Milenkova TP, Tessier J, Krebs AD, Ryan AJ, Fischer R. DCE-MRI assessment of the effect of vandetanib on tumor vasculature in patients with advanced colorectal cancer and liver metastases: a randomized phase I study. J Angiogenes Res. 2009 Sep 21;1:5. doi: 10.1186/2040-2384-1-5.