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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

Phase 2
18 Years
Open (Enrolling)
Kidney Cancer

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Trial Information

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



- 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.


- 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.

Inclusion Criteria


- 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

- No brain metastasis


- 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

- 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


- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Diagnostic

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

Safety Issue:


Principal Investigator

Paul Nathan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mount Vernon Cancer Centre at Mount Vernon Hospital



Study ID:




Start Date:

April 2008

Completion Date:

Related Keywords:

  • Kidney Cancer
  • stage III renal cell cancer
  • stage IV renal cell cancer
  • Carcinoma, Renal Cell
  • Kidney Neoplasms