Kidney CancerPhase 2NCT00873236
MRI Scans of Blood Vessel Changes Caused by Bevacizumab Alone or Given Together With Interferon Alpha-2a in Treating Patients With Stage III or Stage IV Kidney Cancer
A Phase 2 study testing bevacizumab and recombinant interferon alpha-2a in people with Kidney Cancer, run by Mount Vernon Cancer Centre at Mount Vernon Hospital at 5 sites in United Kingdom.
Trial summary
RATIONALE: Comparing results of MRI scans done after bevacizumab may help doctors predict a patient's response to treatment and help plan the best treatment. It is not yet known whether giving bevacizumab alone is more effective than giving bevacizumab together with interferon alpha-2a in detecting kidney cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Cancer
- What is being tested?
- bevacizumab and recombinant interferon alpha-2a
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- Apr 2008to not given
- Phase
- Phase 2
- 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
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed advanced renal cell carcinoma
- Metastatic (stage IV) disease
- Locally advanced (unresectable stage III) disease
- Previously untreated disease
- Majority component of conventional clear-cell type is mandatory (tumors of mixed histology should be categorized by the predominant cell type)
- Good- or intermediate-prognosis disease as defined by Motzer score
- Lesions measurable by RECIST criteria and amenable to dynamic contrast-enhanced MRI scanning
- No brain metastasis
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy ≥ 12 weeks
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 8 g/dL (may be transfused to maintain or exceed this level)
- Total bilirubin < 1.5 times upper limit of normal (ULN)
- AST and ALT < 2.5 times ULN (< 5 times ULN in patients with liver metastases)
- Serum creatinine ≤ 1.5 times ULN
- Urine dipstick for proteinuria < 2+ OR < 1 g of protein in 24-hour urine collection
- INR ≤ 1.5
- Not pregnant or nursing
- Negative pregnancy test
- Fertile women must use effective contraception during and for 9 months after completion of study treatment
- No significant cardiovascular disease, defined as any of the following, within the past 6 months:
- NYHA class II-IV congestive heart failure
- Unstable angina pectoris
- Myocardial infarction
- No significant vascular disease (e.g., aortic aneurysm, aortic dissection) or symptomatic peripheral vacular disease
- No evidence or history of recurrent thromboembolism (> 1 episode of deep venous thrombosis/pulmonary embolism) within the past 6 months, bleeding diathesis, or coagulopathy
- No inadequately controlled hypertension (defined as a BP of > 150 mm Hg systolic and/or > 100 mm Hg diastolic on medication)
- No history of hypertensive crisis or hypertensive encephalopathy
- No stroke or transient ischemic attack within the past 6 months
- No abdominal or tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
- No HIV or hepatitis B or C infection
- No active clinically serious bacterial or fungal infections (> CTCAE grade 2)
- No other infection > CTCAE grade 2
- No concurrent active second malignancy within the past 3 years other than nonmelanoma skin cancers or post-treatment for localized prostate cancer
- No gross ascites
- No seizure disorder requiring medication
- No serious non-healing wound, ulcer, or bone fracture
- No contraindications to MRI scanning (e.g., history of claustrophobia or metal fragment implantation)
- No history of allergic reactions to contrast agents
- No other significant medical illness or medically significant abnormal laboratory finding that would, in the investigator's opinion, make the patient inappropriate for this study, or would increase the risk associated with the patient's participation in the study
PRIOR CONCURRENT THERAPY:
- More than 28 days since prior major surgery (including open biopsy) or radiotherapy and recovered
- More than 14 days since prior palliative radiotherapy to painful bone lesions and recovered
- Concurrent palliative radiotherapy for local pain control allowed
- More than 7 days since prior core biopsy or other minor surgical procedure, excluding placement of a vascular access device
- More than 30 days since prior and no other concurrent investigational agents
- No concurrent chronic daily intake of aspirin ≥ 325 mg/day or clopidogrel > 75 mg/day, or steroids (prednisone > 12.5 mg/day or dexamethasone > 2 mg/day), excluding inhaled steroids
- No concurrent bone marrow transplantation or stem cell rescue
- Concurrent anticoagulation allowed provided INR < 3 and INR is therapeutic on a stable dose of coumarin-type anticoagulation or if patient is on a stable dose of low molecular weight heparin for > 2 weeks at the time of enrollment
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites, 5 recruiting
- Recruiting
Addenbrooke's Hospital
Cambridge, England, CB2 2QQ
Contact Person, 44-1223-245-151
- Recruiting
Royal Marsden - London
London, England, SW3 6JJ
Contact Person, 44-20-7352-8171
- Recruiting
Mount Vernon Cancer Centre at Mount Vernon Hospital
Northwood, England, HA6 2RN
Paul Nathan, MD, 44-192-384-4966
- Recruiting
Churchill Hospital
Oxford, England, OX3 7LJ
Contact Person, 44-186-574-1841
- Recruiting
Royal Marsden - Surrey
Sutton, England, SM2 5PT
Contact Person, 44-20-8642-6011
About this study
Official title: Dynamic Contrast Enhanced MRI (DCE-MRI) Assessment of the Vascular Changes Induced With Bevacizumab Alone and in Combination With Interferon-α in Patients With Advanced Renal Cell Carcinoma
RATIONALE: Comparing results of MRI scans done after bevacizumab may help doctors predict a patient's response to treatment and help plan the best treatment. It is not yet known whether giving bevacizumab alone is more effective than giving bevacizumab together with interferon alpha-2a in detecting kidney cancer.
PURPOSE: This randomized phase II trial is studying MRI scans of blood vessel changes caused by bevacizumab to see how well it works compared with bevacizumab given together with interferon alpha-2a in treating patients with stage III or stage IV kidney cancer.
Read the detailed description
OBJECTIVES:
Primary
- To establish whether bevacizumab-induced changes in dynamic contrast-enhanced (DCE)-MRI vascular parameters are significantly enhanced by recombinant interferon alpha-2a.
- To establish whether there is an interferon alpha-2a dose response in potentiating bevacizumab-induced changes in DCE-MRI vascular parameters.
Secondary
- To correlate changes in DCE-MRI vascular parameters for each treatment group with progression-free survival.
- To correlate changes in DCE-MRI vascular parameters for each treatment group with tumor response and changes in tumor size.
- To correlate changes in DCE-MRI vascular parameters for each treatment group with other surrogate biomarkers.
- To assess the degree of change in baseline K^trans within each arm of treatment.
- To investigate changes in diffusion and blood oxygen-level dependent MRI and their correlation with other pharmacodynamic endpoints.
- To assess the efficacy and safety profile of bevacizumab monotherapy or in combination with low or standard doses of recombinant interferon alpha-2a.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 3 treatment arms.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks.
- Arm II: Patients receive bevacizumab as in arm I and low-dose recombinant interferon alpha-2a subcutaneously (SC) 3 times weekly beginning on day 0.
- Arm III: Patients receive bevacizumab as in arm I and standard-dose recombinant interferon alpha-2a SC 3 times weekly beginning on day 0.
After 8 weeks of treatment, recombinant interferon alpha-2a dosage may be modified or discontinued at the discretion of the investigator. Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients undergo dynamic contrast-enhanced (gadopentetate dimeglumine) MRI scans at baseline and weeks 2 and 6. Peripheral blood and serum samples are collected at baseline and weeks 2, 6, and 8 for analysis of surrogate biomarkers by flow cytometry and mRNA analysis by PCR. Archival histopathological specimens are analyzed by IHC, fluorescence resonance-energy transfer, and fluorescence lifetime-imaging. Urine samples are also collected at baseline for proteomic profiling by MALDI-TOF.
After completion of study treatment, patients are followed at 30 days.
- Conditions
- Kidney Cancer
- Being tested
- bevacizumab, recombinant interferon alpha-2a
- Keywords
- stage III renal cell cancer, stage IV renal cell cancer
- Medical subject headings
- Kidney Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabBiological
Given IV
recombinant interferon alpha-2aBiological
Given SC
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks. Receives: Biological: bevacizumab |
| Arm II | Experimental | Patients receive bevacizumab as in arm I and low-dose recombinant interferon alpha-2a subcutaneously (SC) 3 times weekly beginning on day 0. Receives: Biological: bevacizumab; Biological: recombinant interferon alpha-2a |
| Arm III | Experimental | Patients receive bevacizumab as in arm I and standard-dose recombinant interferon alpha-2a SC 3 times weekly beginning on day 0. Receives: Biological: bevacizumab; Biological: recombinant interferon alpha-2a |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dynamic contrast-enhanced MRI defined changes in K-trans after 6 weeks of bevacizumab monotherapy or bevacizumab and low- or standard-dose recombinant interferon alpha-2a
Secondary outcomes (13)
Change in vascular permeability (K-trans) and tumor hypoxia at 2 and 6 weeks post-commencement of treatment
Best overall response
Progression-free survival
Time to progression
Treatment duration of bevacizumab and recombinant interferon alpha-2a
Treatment withdrawal
Dose modification
Incidence of adverse events
Number of circulating endothelial cells, circulating endothelial progenitors, and proangiogenic monocytic cells
Angiogenic factors (e.g., VEGF) and hypoxia-regulated markers
Correlation of DCE-MRI defined changes in K-trans with clinical response
Correlation of DCE-MRI defined changes in K-trans with surrogate biomarkers
Analysis of diffusion MRI and blood oxygen-level dependent MRI changes and comparison with other pharmacodynamic markers
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2009 (estimated)
- Study startApr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney 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 2
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mount Vernon Cancer Centre at Mount Vernon Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Paul Nathan, MD, Principal investigator, Mount Vernon Cancer Centre at Mount Vernon Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00873236
- Sponsor's protocol ID
- MTVERNHOSP-RD2007-114
- Other IDs
- CDR0000637812, ENH-RD2007-114, EUDRACT-2008-006414-19, EU-20917
- Status last verified
- Mar 2009
- First submitted
- 31 Mar 2009
- Last updated
- 12 Aug 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dynamic Contrast Enhanced MRI (DCE-MRI) Assessment of the Vascular Changes Induced With Bevacizumab Alone and in Combination With Interferon-α in Patients With Advanced Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT00873236
- Acronym / sponsor ID
- MTVERNHOSP-RD2007-114
- Conditions
- Kidney Cancer
- Keywords
- stage III renal cell cancer, stage IV renal cell cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Mount Vernon Cancer Centre at Mount Vernon HospitalUniversity, hospital or other
- Study start
- Apr 2008
- First posted
- 1 Apr 2009 (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.
RATIONALE: Comparing results of MRI scans done after bevacizumab may help doctors predict a patient's response to treatment and help plan the best treatment. It is not yet known whether giving bevacizumab alone is more effective than giving bevacizumab together with interferon alpha-2a in detecting kidney cancer.
PURPOSE: This randomized phase II trial is studying MRI scans of blood vessel changes caused by bevacizumab to see how well it works compared with bevacizumab given together with interferon alpha-2a in treating patients with stage III or stage IV kidney cancer.
Detailed description
OBJECTIVES:
Primary
- To establish whether bevacizumab-induced changes in dynamic contrast-enhanced (DCE)-MRI vascular parameters are significantly enhanced by recombinant interferon alpha-2a.
- To establish whether there is an interferon alpha-2a dose response in potentiating bevacizumab-induced changes in DCE-MRI vascular parameters.
Secondary
- To correlate changes in DCE-MRI vascular parameters for each treatment group with progression-free survival.
- To correlate changes in DCE-MRI vascular parameters for each treatment group with tumor response and changes in tumor size.
- To correlate changes in DCE-MRI vascular parameters for each treatment group with other surrogate biomarkers.
- To assess the degree of change in baseline K^trans within each arm of treatment.
- To investigate changes in diffusion and blood oxygen-level dependent MRI and their correlation with other pharmacodynamic endpoints.
- To assess the efficacy and safety profile of bevacizumab monotherapy or in combination with low or standard doses of recombinant interferon alpha-2a.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 3 treatment arms.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks.
- Arm II: Patients receive bevacizumab as in arm I and low-dose recombinant interferon alpha-2a subcutaneously (SC) 3 times weekly beginning on day 0.
- Arm III: Patients receive bevacizumab as in arm I and standard-dose recombinant interferon alpha-2a SC 3 times weekly beginning on day 0.
After 8 weeks of treatment, recombinant interferon alpha-2a dosage may be modified or discontinued at the discretion of the investigator. Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients undergo dynamic contrast-enhanced (gadopentetate dimeglumine) MRI scans at baseline and weeks 2 and 6. Peripheral blood and serum samples are collected at baseline and weeks 2, 6, and 8 for analysis of surrogate biomarkers by flow cytometry and mRNA analysis by PCR. Archival histopathological specimens are analyzed by IHC, fluorescence resonance-energy transfer, and fluorescence lifetime-imaging. Urine samples are also collected at baseline for proteomic profiling by MALDI-TOF.
After completion of study treatment, patients are followed at 30 days.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Biological: bevacizumabPatients receive bevacizumab IV over 30-90 minutes once every 2 weeks. |
| Arm II | Experimental | Biological: bevacizumab, Biological: recombinant interferon alpha-2aPatients receive bevacizumab as in arm I and low-dose recombinant interferon alpha-2a subcutaneously (SC) 3 times weekly beginning on day 0. |
| Arm III | Experimental | Biological: bevacizumab, Biological: recombinant interferon alpha-2aPatients receive bevacizumab as in arm I and standard-dose recombinant interferon alpha-2a SC 3 times weekly beginning on day 0. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| bevacizumabGiven IV | Biological | Arm I, Arm II, Arm III |
| recombinant interferon alpha-2aGiven SC | Biological | Arm II, Arm III |
Primary outcome
Dynamic contrast-enhanced MRI defined changes in K-trans after 6 weeks of bevacizumab monotherapy or bevacizumab and low- or standard-dose recombinant interferon alpha-2a
13 secondary outcomes
Change in vascular permeability (K-trans) and tumor hypoxia at 2 and 6 weeks post-commencement of treatment
Best overall response
Progression-free survival
Time to progression
Treatment duration of bevacizumab and recombinant interferon alpha-2a
Treatment withdrawal
Dose modification
Incidence of adverse events
Number of circulating endothelial cells, circulating endothelial progenitors, and proangiogenic monocytic cells
Angiogenic factors (e.g., VEGF) and hypoxia-regulated markers
Correlation of DCE-MRI defined changes in K-trans with clinical response
Correlation of DCE-MRI defined changes in K-trans with surrogate biomarkers
Analysis of diffusion MRI and blood oxygen-level dependent MRI changes and comparison with other pharmacodynamic markers
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2013.
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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.
Paul Nathan, MD principal investigator
Mount Vernon Cancer Centre at Mount Vernon Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bevacizumab and recombinant interferon alpha-2a in people with Kidney Cancer, run by Mount Vernon Cancer Centre at Mount Vernon Hospital at 5 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 12 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dynamic contrast-enhanced MRI defined changes in K-trans after 6 weeks of bevacizumab monotherapy or bevacizumab and low- or standard-dose recombinant interferon alpha-2a. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Aug 2013.