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

NCT ID: NCT00873236

Last Updated: 2013-08-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Kidney Cancer

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

stage III renal cell cancer stage IV renal cell cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm I

Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks.

Group Type EXPERIMENTAL

bevacizumab

Intervention Type BIOLOGICAL

Given IV

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.

Group Type EXPERIMENTAL

bevacizumab

Intervention Type BIOLOGICAL

Given IV

recombinant interferon alpha-2a

Intervention Type BIOLOGICAL

Given SC

Arm III

Patients receive bevacizumab as in arm I and standard-dose recombinant interferon alpha-2a SC 3 times weekly beginning on day 0.

Group Type EXPERIMENTAL

bevacizumab

Intervention Type BIOLOGICAL

Given IV

recombinant interferon alpha-2a

Intervention Type BIOLOGICAL

Given SC

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

bevacizumab

Given IV

Intervention Type BIOLOGICAL

recombinant interferon alpha-2a

Given SC

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Mount Vernon Cancer Centre at Mount Vernon Hospital

OTHER

Sponsor Role lead

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Paul Nathan, MD

Role: PRINCIPAL_INVESTIGATOR

Mount Vernon Cancer Centre at Mount Vernon Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Site Status RECRUITING

Royal Marsden - London

London, England, United Kingdom

Site Status RECRUITING

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood, England, United Kingdom

Site Status RECRUITING

Churchill Hospital

Oxford, England, United Kingdom

Site Status RECRUITING

Royal Marsden - Surrey

Sutton, England, United Kingdom

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United Kingdom

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Contact Person

Role: primary

Contact Person

Role: primary

Paul Nathan, MD

Role: primary

Contact Person

Role: primary

Contact Person

Role: primary

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CDR0000637812

Identifier Type: REGISTRY

Identifier Source: secondary_id

ENH-RD2007-114

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2008-006414-19

Identifier Type: -

Identifier Source: secondary_id

EU-20917

Identifier Type: -

Identifier Source: secondary_id

MTVERNHOSP-RD2007-114

Identifier Type: -

Identifier Source: org_study_id