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CompletedNCT00853021Updated Jun 5, 2019Results posted

Bevacizumab and Aldesleukin in Treating Patients With Metastatic Clear Cell Carcinoma of the Kidney

A Phase 2 interventional study of aldesleukin and bevacizumab in Kidney Cancer, sponsored by Jorge A. Garcia, MD. Completed at 1 site in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2019-06-05.

Sponsored by Jorge A. Garcia, MD · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
26
Allocation
Not applicable
Ages
18 Years to 120 Years
Sex
All
01

Study summary

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Biological therapies, such as aldesleukin, may stimulate the immune system in different ways and stop tumor cells from growing. Giving bevacizumab together with aldesleukin may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with aldesleukin works in treating patients with metastatic clear cell carcinoma of the kidney.

Read the detailed description

OBJECTIVES:

Primary

  • To evaluate the effect of the combination of bevacizumab and aldesleukin on progression-free survival of patients with good- or intermediate-risk metastatic clear cell renal cell carcinoma.

Secondary

  • To determine the objective response rate in patients receiving this regimen.
  • To determine the time to progression in patients receiving this regimen.
  • To evaluate immunomodulatory effects of this regimen in patients
  • To evaluate the toxicity of this regimen in these patients.

OUTLINE: Patients receive bevacizumab IV over 30-90 minutes on days -14, 1, 15, 29, and 42 and aldesleukin subcutaneously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Courses repeat every 8 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving complete response after completion of study therapy may receive 1 additional course of therapy.

After completion of study therapy, patients are followed periodically.

02

Conditions studied

  • Kidney Cancer

Keywords

  • clear cell renal cell carcinoma
  • recurrent renal cell cancer
  • stage IV renal cell cancer
03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 26 is below the median of 45 across 5,170 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

Jorge A. Garcia, MD is the lead sponsor of 2 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 120 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed renal cell carcinoma (RCC) of clear cell histology with or without sarcomatoid features

    • Metastatic disease
    • No non-clear cell RCC (i.e., papillary, collecting-duct, or chromophobe)

  • Good- or intermediate-risk category as defined by having ≤ 2 of the following factors:

    • No prior nephrectomy
    • Karnofsky performance status \< 80%
    • Hemoglobin \< 12 g/dL
    • Corrected calcium > 10.0 mg/dL
    • LDH > 1.5 times upper limit of normal (ULN)
  • Must have undergone a nephrectomy at least 28 days ago
  • Measurable or evaluable disease by RECIST
  • No significant effusions and/or ascites
  • No prior or concurrent brain or CNS metastasis

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy of ≥ 3 months
  • WBC ≥ 3,000/mm\^3
  • Platelet count ≥ 100,000/mm\^3
  • Hemoglobin ≥ 9.5 g/dL
  • Creatinine ≤ 2.0 mg/dL
  • Total bilirubin ≤ 1.5 mg/dL
  • AST ≤ 5.0 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN (≤ 10 times ULN with bone metastasis)
  • Calcium ≤ 12 mg/dL
  • Urine protein:creatinine ratio ≤ 1.0
  • INR ≤ 1.5 (unless receiving warfarin therapy)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled seizure disorder
  • No known HIV positivity
  • No local or systemic infections requiring IV antibiotics within the past 28 days
  • No significant traumatic injury in the past 28 days
  • No serious non-healing wound, ulcer, or acute bone fracture
  • No evidence of bleeding diathesis or coagulopathy
  • No other malignancy except basal cell or squamous cell carcinoma of the skin, carcinoma in-situ of the uterine cervix, or any malignancy treated with curative intent and in complete remission for > 3 years

  • No history of serious systemic or severe cardiovascular disease, including any of the following:

    • Arterial thromboembolic event (including transient ischemic attack)
    • Cerebrovascular accident
    • Unstable angina
    • Myocardial infarction within the past 6 months
    • Uncontrolled hypertension (BP > 160/110 mm Hg on medication)
    • Uncontrolled cardiac arrhythmia
    • Congestive heart failure
    • Angina pectoris
    • NYHA class III-IV cardiovascular disease
    • Peripheral vascular disease ≥ grade II
  • No history of abdominal fistula and/or bowel or gastric perforation within the past 6 months
  • No history of other diseases, metabolic dysfunction, or physical or laboratory examination findings giving reasonable suspicion of a disease or condition that contraindicate the use of investigational drugs, or that might affect the interpretation of study results, or that render patient at high-risk for treatment complications

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior organ allografts
  • No prior systemic therapy for metastatic clear cell renal cell carcinoma

  • At least 4 weeks since prior radiotherapy and recovered

    • Radiotherapy for control of pain from skeletal lesions allowed within the past 28 days
  • More than 12 months since prior adjuvant therapy
  • More than 7 days since prior fine-needle aspirations or core biopsies
  • More than 28 days since prior and no concurrent major surgery requiring general anesthesia or open biopsy
  • No concurrent aspirin, corticosteroids (except at replacement doses), barbiturates, or other investigational agents
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
26 participants (actual)

Study arms

  • Experimental
    Bevacizumab and Aldesleukin

    Biological: aldesleukin · Biological: bevacizumab

Interventions

  • Biologicalaldesleukin

    SQ Aldesleukin (Days 1-5) Monday through Friday for six weeks followed by a two-week break.

    Also known as: rIL-2 (NSC3773364), Proleukin®, Chiron

  • Biologicalbevacizumab

    Bevacizumab will be administered on day -14, then on day 1 and every 2 weeks thereafter (days 1, 15, 29, and 42) in a continuous manner.

06

What researchers measure

Primary outcomes

  1. Progression Free Survival

    Progression free survival is defined as the time between registration and progression of disease as defined by the RECIST criteria where there is a 20% increase in the diameter of the tumor and at least a 5mm absolute increase in diameter.

    Time frame: From baseline (day -14) to disease progression (reported at 2 years)

Secondary outcomes

  1. Objective Response Rate (Complete and Partial Response)

    Objective response rate to be assigned a status of PR or CR per RECIST criteria, with Complete Response (CR) referring to the disappearance of all target lesions, Partial Response (PR) referring to at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met.

    Time frame: 4 weeks after end of treatment

  2. Percentage of Patients With Constitutional Adverse Events

    Toxicity Criteria: The NCI graded common clinical toxicity scale (NCI Version 2.0) will be employed to grade observed toxicity of fatigue and fever/chills

    Time frame: From start of treatment to 30 days after treatment

  3. Percentage of Patients With Neutropenia

    Toxicity Criteria: The NCI graded common clinical toxicity scale (NCI Version 2.0) will be employed to grade observed toxicity of neutropenia

    Time frame: From start of treatment to 30 days after treatment

Other outcomes

  1. Peripheral Blood CD1c+ Myeloid Dendritic Cells

    Peripheral blood mononuclear cells (PBMC) and plasma were separated by centrifugation. Targeted cells were isolated by a magnetic labeling system. Total RNA was isolated and then amplified by (Polymerase Chain Reactions) PCR to measure levels of the immune parameter.

    Time frame: Baseline (day -14), Beginning and end of cycle 1 (day 1, 57)

  2. CD303+ Plasmacytoid Dendritic Cells

    Peripheral blood mononuclear cells (PBMC) and plasma were separated by centrifugation. Targeted cells were isolated by a magnetic labeling system. Total RNA was isolated and then amplified by (Polymerase Chain Reactions) PCR to measure levels of the immune parameter.

    Time frame: Baseline (day -14), beginning and end of cycle 1 (day 1, 57)

  3. IL-8 Levels

    Peripheral blood mononuclear cells (PBMC) and plasma were separated by centrifugation. Targeted cells were isolated by a magnetic labeling system. Total RNA was isolated and then amplified by (Polymerase Chain Reactions) PCR to measure levels of the immune parameter.

    Time frame: Baseline (day -14), beginning and end of cycle 1 (day 1, 57)

  4. CD4+ Treg Cells

    Peripheral blood mononuclear cells (PBMC) and plasma were separated by centrifugation. Targeted cells were isolated by a magnetic labeling system. Total RNA was isolated and then amplified by (Polymerase Chain Reactions) PCR to measure levels of the immune parameter.

    Time frame: Baseline (day -14), beginning and end of cycle 1 (day 1, 57)

  5. CD25+ Treg Cells

    Peripheral blood mononuclear cells (PBMC) and plasma were separated by centrifugation. Targeted cells were isolated by a magnetic labeling system. Total RNA was isolated and then amplified by (Polymerase Chain Reactions) PCR to measure levels of the immune parameter.

    Time frame: Baseline (day -14), beginning and end of cycle 1 (day 1, 57)

  6. T-helper Cells (Type 1,2)

    Peripheral blood mononuclear cells (PBMC) and plasma were separated by centrifugation. Targeted cells were isolated by a magnetic labeling system. Total RNA was isolated and then amplified by (Polymerase Chain Reactions) PCR to measure levels of the immune parameter.

    Time frame: Baseline (day -14), beginning and end of cycle 1 (day 1, 57)

07

Results

Posted Aug 24, 2015

Participant flow

Participant flow — Overall Study
MilestoneBevacizumab and Aldesleukin
Started26
Completed21
Not completed5
Withdrew: Adverse event2
Withdrew: Withdrawal by subject2
Withdrew: Death1

Outcome measures

PrimaryProgression Free Survival

Progression free survival is defined as the time between registration and progression of disease as defined by the RECIST criteria where there is a 20% increase in the diameter of the tumor and at least a 5mm absolute increase in diameter.

Time frame:
From baseline (day -14) to disease progression (reported at 2 years)
Reported as:
Median · months
Progression Free Survival
monthsBevacizumab and Aldesleukin
Progression Free Survival9.6 (4.1 to 16.9)
SecondaryObjective Response Rate (Complete and Partial Response)

Objective response rate to be assigned a status of PR or CR per RECIST criteria, with Complete Response (CR) referring to the disappearance of all target lesions, Partial Response (PR) referring to at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met.

Time frame:
4 weeks after end of treatment
Reported as:
Number · percentage of participants
Objective Response Rate (Complete and Partial Response)
percentage of participantsBevacizumab and Aldesleukin
Objective Response Rate (Complete and Partial Response)15
SecondaryPercentage of Patients With Constitutional Adverse Events

Toxicity Criteria: The NCI graded common clinical toxicity scale (NCI Version 2.0) will be employed to grade observed toxicity of fatigue and fever/chills

Time frame:
From start of treatment to 30 days after treatment
Reported as:
Number · percentage of patients
Percentage of Patients With Constitutional Adverse Events
percentage of patientsBevacizumab and Aldesleukin
Percentage of Patients With Constitutional Adverse Events42
SecondaryPercentage of Patients With Neutropenia

Toxicity Criteria: The NCI graded common clinical toxicity scale (NCI Version 2.0) will be employed to grade observed toxicity of neutropenia

Time frame:
From start of treatment to 30 days after treatment
Reported as:
Number · percentage of participants
Percentage of Patients With Neutropenia
percentage of participantsBevacizumab and Aldesleukin
Percentage of Patients With Neutropenia12
Other pre-specifiedPeripheral Blood CD1c+ Myeloid Dendritic Cells

Peripheral blood mononuclear cells (PBMC) and plasma were separated by centrifugation. Targeted cells were isolated by a magnetic labeling system. Total RNA was isolated and then amplified by (Polymerase Chain Reactions) PCR to measure levels of the immune parameter.

Time frame:
Baseline (day -14), Beginning and end of cycle 1 (day 1, 57)

Results for this outcome have not been posted.

Other pre-specifiedCD303+ Plasmacytoid Dendritic Cells

Peripheral blood mononuclear cells (PBMC) and plasma were separated by centrifugation. Targeted cells were isolated by a magnetic labeling system. Total RNA was isolated and then amplified by (Polymerase Chain Reactions) PCR to measure levels of the immune parameter.

Time frame:
Baseline (day -14), beginning and end of cycle 1 (day 1, 57)

Results for this outcome have not been posted.

Other pre-specifiedIL-8 Levels

Peripheral blood mononuclear cells (PBMC) and plasma were separated by centrifugation. Targeted cells were isolated by a magnetic labeling system. Total RNA was isolated and then amplified by (Polymerase Chain Reactions) PCR to measure levels of the immune parameter.

Time frame:
Baseline (day -14), beginning and end of cycle 1 (day 1, 57)

Results for this outcome have not been posted.

Other pre-specifiedCD4+ Treg Cells

Peripheral blood mononuclear cells (PBMC) and plasma were separated by centrifugation. Targeted cells were isolated by a magnetic labeling system. Total RNA was isolated and then amplified by (Polymerase Chain Reactions) PCR to measure levels of the immune parameter.

Time frame:
Baseline (day -14), beginning and end of cycle 1 (day 1, 57)

Results for this outcome have not been posted.

Other pre-specifiedCD25+ Treg Cells

Peripheral blood mononuclear cells (PBMC) and plasma were separated by centrifugation. Targeted cells were isolated by a magnetic labeling system. Total RNA was isolated and then amplified by (Polymerase Chain Reactions) PCR to measure levels of the immune parameter.

Time frame:
Baseline (day -14), beginning and end of cycle 1 (day 1, 57)

Results for this outcome have not been posted.

Other pre-specifiedT-helper Cells (Type 1,2)

Peripheral blood mononuclear cells (PBMC) and plasma were separated by centrifugation. Targeted cells were isolated by a magnetic labeling system. Total RNA was isolated and then amplified by (Polymerase Chain Reactions) PCR to measure levels of the immune parameter.

Time frame:
Baseline (day -14), beginning and end of cycle 1 (day 1, 57)

Results for this outcome have not been posted.

Adverse events

Collected over 18 Months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Bevacizumab and Aldesleukin—9/26 (34.6%)26/26 (100%)
Most frequent serious events
Showing 10 of 13
Most frequent serious events
EventBevacizumab and Aldesleukin
Heart failureCardiac disorders2/26
Infection without neutropeniaInfections and infestations2/26
HypercalcemiaMetabolism and nutrition disorders1/26
Abdominal pain or crampingGastrointestinal disorders1/26
AscitesGastrointestinal disorders1/26
ConfusionPsychiatric disorders1/26
DiarrheaGastrointestinal disorders1/26
DyspneaRespiratory, thoracic and mediastinal disorders1/26
Hepatic failureHepatobiliary disorders1/26
HyperkalemiaMetabolism and nutrition disorders1/26
Most frequent other events
Showing 10 of 55
Most frequent other events
EventBevacizumab and Aldesleukin
Fatigue (lethargy, malaise, asthenia)General disorders26/26
Rigors, chillsGeneral disorders26/26
NauseaGastrointestinal disorders22/26
AnorexiaGastrointestinal disorders21/26
Injection site reactionGeneral disorders20/26
DiarrheaGastrointestinal disorders18/26
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 10e9/L)General disorders18/26
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)Respiratory, thoracic and mediastinal disorders13/26
Weight lossInvestigations13/26
vomitingGastrointestinal disorders12/26

Baseline characteristics

Age, Continuous
Age, Continuous(years)Bevacizumab and Aldesleukin
Mean59.4 ± 6.7
Sex: Female, Male
Sex: Female, Male(Participants)Bevacizumab and Aldesleukin
Female4
Male22
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Bevacizumab and Aldesleukin
Hispanic or Latino0
Not Hispanic or Latino25
Unknown or Not Reported1
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Bevacizumab and Aldesleukin
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White25
More than one race0
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(participants)Bevacizumab and Aldesleukin
United States26
08

Study locations

1 site
  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
    Cleveland, Ohio 44195, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 5, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00853021
Lead sponsor
Jorge A. Garcia, MD
Collaborators
National Cancer Institute (NCI)
Responsible party
Jorge A. Garcia, MD (Principal Investigator, Case Comprehensive Cancer Center) — Sponsor-investigator
First posted
Feb 27, 2009
Start date
Dec 2005
Primary completion
Oct 2009
Completion
Oct 2009
Results posted
Aug 24, 2015
Last update
Jun 5, 2019

Study contacts

Jorge A. Garcia, MD
principal investigator · Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

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