Colorectal CancerPhase 1NCT00496509
Phase I Efficacy On Vascular Permeability In Patients With Advanced Colorectal Cancer
A Phase 1 study testing ZD6474 (Zactima) 100mg, Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MR) and Biomarker Draws in people with Colorectal Cancer, run by Genzyme, a Sanofi Company at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- ZD6474 (Zactima) 100mg, Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MR) and Biomarker Draws
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2006to Oct 2007
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 25Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Colorectal Cancer
- Being tested
- ZD6474 (Zactima) 100mg, Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MR), Biomarker Draws, ZD6474 (Zactima) 300mg
- Keywords
- ZD6474, Colorectal Cancer, Liver Metastases, Biomarkers
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZD6474 (Zactima) 100mgDrug
Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MR)Procedure or surgery
Biomarker DrawsProcedure or surgery
ZD6474 (Zactima) 300mgDrug
| Study group | Role | What they receive |
|---|---|---|
| ZD6474 (vandetanib) 100mg | Experimental | Not described Receives: Drug: ZD6474 (Zactima) 100mg; Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MR); Procedure: Biomarker Draws |
| ZD6474 (vandetanib) 300mg | Experimental | Not described Receives: Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MR); Procedure: Biomarker Draws; Drug: ZD6474 (Zactima) 300mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 57 days.
Secondary outcomes (3)
Assessment of appropriate Pharmacokinetic parameters
The exposure to ZD6474 in patients with advanced colorectal cancer and liver metastases by assessment of: maximum plasma concentration after single and at steady state (C max and Css, max); time to reach C max and Css, max (tmax); minimum plasma concentration before and at steady state (Cmin and Css, min); area under plasma concentration-time curve from zero to 24 h and at steady state (AUC(0-24) and AUCss); total body clearance of drug from plasma after an oral dose (CL/F): accumulation ratio (Rac) and fraction of ZD6474 unbound (fu).
Measured: Predetermined timepoints after dose administration
Determine the population PK of ZD6474 and assess the relationship between both free and total plasma PK and measures of Pharmacological activity
Determination of the population PK of ZD6474 and the assessment of the relationship between both free and total plasma PK and measures of pharmacological activity by assessment of individual predicted plasma concentrations, individual predicted CL/F, AUCss, Css, max, and AUC to the point up to the scan.
Measured: Predetermined timepoints after dose administration
Assessment of the effectiveness of ZD6474 as measured by objective response rate and progression free survival based on RECIST.
Measured: Every 8 weeks during the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2007 (estimated)
- Study startAug 2006
- Primary completionOct 2007
- Study completionOct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Principal investigator, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00496509
- Sponsor's protocol ID
- D4200C00050
- Status last verified
- Aug 2016
- First submitted
- 3 Jul 2007
- Last updated
- 26 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19946413
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00496509
- Acronym / sponsor ID
- D4200C00050
- Conditions
- Colorectal Cancer
- Keywords
- ZD6474, Colorectal Cancer, Liver Metastases, Biomarkers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Aug 2006
- Primary completion
- Oct 2007 (actual)
- Study completion
- Oct 2007 (actual)
- First posted
- 4 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ZD6474 (vandetanib) 100mg | Experimental | Drug: ZD6474 (Zactima) 100mg, Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MR), Procedure: Biomarker Draws |
| ZD6474 (vandetanib) 300mg | Experimental | Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MR), Procedure: Biomarker Draws, Drug: ZD6474 (Zactima) 300mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZD6474 (Zactima) 100mg | Drug | ZD6474 (vandetanib) 100mg |
| Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MR) | Procedure or surgery | ZD6474 (vandetanib) 100mg, ZD6474 (vandetanib) 300mg |
| Biomarker Draws | Procedure or surgery | ZD6474 (vandetanib) 100mg, ZD6474 (vandetanib) 300mg |
| ZD6474 (Zactima) 300mg | Drug | ZD6474 (vandetanib) 300mg |
Primary outcome
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.
Time frame: Up to 57 days.
3 secondary outcomes
Assessment of appropriate Pharmacokinetic parameters
Time frame: Predetermined timepoints after dose administration
Determine the population PK of ZD6474 and assess the relationship between both free and total plasma PK and measures of Pharmacological activity
Time frame: Predetermined timepoints after dose administration
Assessment of the effectiveness of ZD6474 as measured by objective response rate and progression free survival based on RECIST.
Time frame: Every 8 weeks during the study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2016.
- Background: PubMed 19946413Mross 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.
Related trials for Colorectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations principal investigator
Sanofi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ZD6474 (Zactima) 100mg, Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MR) and Biomarker Draws in people with Colorectal Cancer, run by Genzyme, a Sanofi Company at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: Up to 57 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00496509, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2016.