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

Phase II Open Label Trial of rIL-2 and Bevacizumab Combination in Patients With Metastatic Clear Cell Renal Carcinoma

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00853021
Enrollment
26
Registered
2009-02-27
Start date
2005-12-31
Completion date
2009-10-31
Last updated
2019-06-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Kidney Cancer

Keywords

clear cell renal cell carcinoma, recurrent renal cell cancer, stage IV renal cell cancer

Brief 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.

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.

Interventions

BIOLOGICALaldesleukin

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

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.

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Jorge A. Garcia, MD
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No

Inclusion 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

Design outcomes

Primary

MeasureTime frameDescription
Progression Free SurvivalFrom baseline (day -14) to disease progression (reported at 2 years)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.

Secondary

MeasureTime frameDescription
Objective Response Rate (Complete and Partial Response)4 weeks after end of treatmentObjective 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.
Percentage of Patients With Constitutional Adverse EventsFrom start of treatment to 30 days after treatmentToxicity Criteria: The NCI graded common clinical toxicity scale (NCI Version 2.0) will be employed to grade observed toxicity of fatigue and fever/chills
Percentage of Patients With NeutropeniaFrom start of treatment to 30 days after treatmentToxicity Criteria: The NCI graded common clinical toxicity scale (NCI Version 2.0) will be employed to grade observed toxicity of neutropenia

Other

MeasureTime frameDescription
CD25+ Treg CellsBaseline (day -14), beginning and end of cycle 1 (day 1, 57)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.
Peripheral Blood CD1c+ Myeloid Dendritic CellsBaseline (day -14), Beginning and end of cycle 1 (day 1, 57)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.
T-helper Cells (Type 1,2)Baseline (day -14), beginning and end of cycle 1 (day 1, 57)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.
CD303+ Plasmacytoid Dendritic CellsBaseline (day -14), beginning and end of cycle 1 (day 1, 57)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.
IL-8 LevelsBaseline (day -14), beginning and end of cycle 1 (day 1, 57)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.
CD4+ Treg CellsBaseline (day -14), beginning and end of cycle 1 (day 1, 57)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.

Countries

United States

Participant flow

Participants by arm

ArmCount
Bevacizumab and Aldesleukin
aldesleukin: SQ Aldesleukin (Days 1-5) Monday through Friday for six weeks followed by a two-week break. bevacizumab: 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.
26
Total26

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyAdverse Event2
Overall StudyDeath1
Overall StudyWithdrawal by Subject2

Baseline characteristics

CharacteristicBevacizumab and Aldesleukin
Age, Continuous59.4 years
STANDARD_DEVIATION 6.7
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
25 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
0 Participants
Race (NIH/OMB)
Black or African American
0 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants
Race (NIH/OMB)
White
25 Participants
Region of Enrollment
United States
26 participants
Sex: Female, Male
Female
4 Participants
Sex: Female, Male
Male
22 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
26 / 26
serious
Total, serious adverse events
9 / 26

Outcome results

Primary

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)

ArmMeasureValue (MEDIAN)
Bevacizumab and AldesleukinProgression Free Survival9.6 months
Secondary

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

ArmMeasureValue (NUMBER)
Bevacizumab and AldesleukinObjective Response Rate (Complete and Partial Response)15 percentage of participants
Secondary

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

ArmMeasureValue (NUMBER)
Bevacizumab and AldesleukinPercentage of Patients With Constitutional Adverse Events42 percentage of patients
Secondary

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

ArmMeasureValue (NUMBER)
Bevacizumab and AldesleukinPercentage of Patients With Neutropenia12 percentage of participants
Other Pre-specified

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)

Other Pre-specified

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)

Other Pre-specified

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)

Other Pre-specified

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)

Other Pre-specified

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)

Other Pre-specified

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)

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026