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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

Primary Purpose

Kidney Cancer

Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
bevacizumab
recombinant interferon alpha-2a
Sponsored by
Mount Vernon Cancer Centre at Mount Vernon Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Kidney Cancer focused on measuring stage III renal cell cancer, stage IV renal cell cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Addenbrooke's HospitalRecruiting
  • Royal Marsden - LondonRecruiting
  • Mount Vernon Cancer Centre at Mount Vernon HospitalRecruiting
  • Churchill HospitalRecruiting
  • Royal Marsden - SurreyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm I

Arm II

Arm III

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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 Outcome Measures

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

Full Information

First Posted
March 31, 2009
Last Updated
August 9, 2013
Sponsor
Mount Vernon Cancer Centre at Mount Vernon Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00873236
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2009
Overall Recruitment Status
Unknown status
Study Start Date
April 2008 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Mount Vernon Cancer Centre at Mount Vernon Hospital

4. Oversight

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Cancer
Keywords
stage III renal cell cancer, stage IV renal cell cancer

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks.
Arm Title
Arm II
Arm Type
Experimental
Arm Description
Patients receive bevacizumab as in arm I and low-dose recombinant interferon alpha-2a subcutaneously (SC) 3 times weekly beginning on day 0.
Arm Title
Arm III
Arm Type
Experimental
Arm Description
Patients receive bevacizumab as in arm I and standard-dose recombinant interferon alpha-2a SC 3 times weekly beginning on day 0.
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
recombinant interferon alpha-2a
Intervention Description
Given SC
Primary Outcome Measure Information:
Title
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 Outcome Measure Information:
Title
Change in vascular permeability (K-trans) and tumor hypoxia at 2 and 6 weeks post-commencement of treatment
Title
Best overall response
Title
Progression-free survival
Title
Time to progression
Title
Treatment duration of bevacizumab and recombinant interferon alpha-2a
Title
Treatment withdrawal
Title
Dose modification
Title
Incidence of adverse events
Title
Number of circulating endothelial cells, circulating endothelial progenitors, and proangiogenic monocytic cells
Title
Angiogenic factors (e.g., VEGF) and hypoxia-regulated markers
Title
Correlation of DCE-MRI defined changes in K-trans with clinical response
Title
Correlation of DCE-MRI defined changes in K-trans with surrogate biomarkers
Title
Analysis of diffusion MRI and blood oxygen-level dependent MRI changes and comparison with other pharmacodynamic markers

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Nathan, MD
Organizational Affiliation
Mount Vernon Cancer Centre at Mount Vernon Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Addenbrooke's Hospital
City
Cambridge
State/Province
England
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-1223-245-151
Facility Name
Royal Marsden - London
City
London
State/Province
England
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-20-7352-8171
Facility Name
Mount Vernon Cancer Centre at Mount Vernon Hospital
City
Northwood
State/Province
England
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul Nathan, MD
Phone
44-192-384-4966
Facility Name
Churchill Hospital
City
Oxford
State/Province
England
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-186-574-1841
Facility Name
Royal Marsden - Surrey
City
Sutton
State/Province
England
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
44-20-8642-6011

12. IPD Sharing Statement

Learn more about this trial

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

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