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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT00520533
Registration number
NCT00520533
Ethics application status
Date submitted
22/08/2007
Date registered
24/08/2007
Date last updated
12/10/2022
Titles & IDs
Public title
Study of Safety and Functional Imaging of cG250 and Sunitinib in Patients With Advanced Renal Cell Carcinoma
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Scientific title
A Pilot Study of the Safety, Efficacy, and Effects on Functional Imaging of the Combination of cG250 and Sunitinib in Patients With Advanced Renal Cell Carcinoma
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Secondary ID [1]
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LUD2007-004
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma (RCC)
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Condition category
Condition code
Cancer
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Non melanoma skin cancer
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Cancer
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Kidney
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Chimeric monoclonal antibody cG250
Treatment: Drugs - Sunitinib malate
Experimental: On Study - Treatment (cycle 1):
cG250 10mg/m² IV weekly x 5 doses (1st & 5th doses trace-labelled with 124I)
Sunitinib 50 mg/day orally x 4 weeks commencing day 8
Followed by two-week break
Treatment (cycle 2 - investigator discretion):
cG250 10mg/m² IV weekly x4 doses
Sunitinib 50 mg/day orally x 4 weeks (commencing concurrently)
Followed by two-week break
Other interventions: Chimeric monoclonal antibody cG250
First Cycle: cG250 10 mg/m² intravenous infusion, weekly for five weeks, followed by a two-week break. 1st & 5th dose will be trace-labeled with a radioactive substance detectable on a PET scanner (124I-cG250).
Second cycle (investigator discretion): cG250 10 mg/m² intravenous infusion, weekly for four weeks followed by a two-week break. No 124I-cG250 will be used in the 2nd cycle.
Up to 2 cycles available.
Treatment: Drugs: Sunitinib malate
First Cycle: Sunitinib 50 mg orally daily for 4 weeks (starts 8th day of 1st treatment cycle), followed by a two-week period off sunitinib.
Second cycle (investigator discretion): Sunitinib 50 mg orally daily for 4 weeks (starts on 1st day of 2nd treatment cycle), followed by a two-week period off sunitinib.
Up to 2 cycles available on-study.
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Intervention code [1]
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Other interventions
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Intervention code [2]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs), Dose Limiting Toxicities (DLTs) or Adverse Events Leading to Discontinuation.
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Assessment method [1]
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Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were reported based on clinical laboratory tests, vital sign, weight measurements, physical examinations, and performance status evaluations. Pre-existing symptoms were collected from the signing of informed consent until the first dose of study drug. Adverse events were collected from the first dose of study drug through the end of study assessment.
Dose Limiting Toxicity (DLT): any of the following events occurring within 30 days of study drug administration related to cG250 or sunitinib.
Grade 2 or greater allergic reaction. Grade 3 toxicity. Exceptions are: fever; asymptomatic hyperglycemia; hypophosphatemia; nausea, vomiting, or diarrhoea that resolve with medical therapy; leukopenia or thrombocytopenia that revert to baseline within three weeks of occurrence, or lymphopenia only.
Any Grade 4 toxicity.
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Timepoint [1]
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up to 14 weeks
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Secondary outcome [1]
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Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST).
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Assessment method [1]
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Tumor responses were evaluated using appropriate imaging and categorized according to RECIST at Screening (within 4 weeks of the first dose of study treatment), and after cycles 1 and 2 of study treatment. Per RECIST, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): = 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD): = 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria (Therasse et al 2000).
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Timepoint [1]
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up to 14 weeks
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Secondary outcome [2]
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Number of Patients With Tumor Metabolic Response as Assessed by Serial 18F-FDG-PET Scans.
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Assessment method [2]
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18F-FDG-PET was performed at pre-study, between days 15-22 and at the end of cycle 1. At baseline, visual grading of the intensity of FDG uptake was scored. On follow-up PET scans, the greatest baseline maximum standard uptake value (SUVmax) of the reference lesion with the greatest baseline value and presence/absence of new sites of disease were recorded.
Tumour metabolic response was calculated using the SUVmax and was categorized according to the EORTC guidelines (Young et al 1999).
Complete metabolic remission (CMR) is the disappearance of tracer uptake in the target lesion and no new lesions; Partial metabolic remission (PMR) is a 20% or more decrease in the tracer uptake in the target lesion and no new lesions; Tumor progression was defined as a greater than 20% increase in FDG uptake or the appearance of new tumour lesions. Stable metabolic disease (SMD) was classified as no significant change in uptake.
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Timepoint [2]
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7 weeks
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Secondary outcome [3]
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Whole Body Clearance as Measured by Mean Biological Half-life (T1/2) After the First and Fifth Infusions of 124I-cG250.
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Assessment method [3]
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Biological half-life is the clearance of the 124I from the whole body. Positron emission tomography (PET) imaging was performed at 1 - 4 hours post infusion, and at two other time points over the ensuing one-week period.
Quantitative uptakes of 124I-cG250 were assessed in one selected reference tumour lesion identified by 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (18F-FDG) PET imaging. Tumour volume of Interest (VOI) was delineated around the whole tumour mass on the consecutive transverse slices of FDG-PET/CT images at which the tumours were most clearly identified.
Whole body clearance of 124I-cG250 was calculated from the whole body PET volumetric images, obtained at the multiple imaging time points after infusion. VOIs were delineated to encompass the whole body regions in the images, and for the whole-body VOI at each time point, the total counts per minute was normalized to the first imaging time point on Day 1.
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Timepoint [3]
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7 weeks
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Secondary outcome [4]
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Whole Body Clearance as Measured by Mean Effective Half-life (T1/2) After the First and Fifth Infusions of 124I-cG250.
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Assessment method [4]
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Effective half-life is the time it takes the radiolabel to be reduced by 50%. This takes into account the biological elimination and the radioactive decay of the 124I.
PET imaging studies were performed at 1 - 4 hours post infusion, and at two other time points over the ensuing one-week period.
Quantitative uptakes of 124I-cG250 were assessed in one selected reference tumour lesion identified by 18F-FDG-PET imaging. Tumour volume of Interest (VOI) was delineated around the whole tumour mass on the consecutive transverse slices of FDG-PET/CT images at which the tumours were most clearly identified.
Whole body clearance of 124I-cG250 was calculated from the whole body PET volumetric images, obtained at the multiple imaging time points after infusion. VOIs were delineated to encompass the whole body regions in the images, and for the whole-body VOI at each time point, the total counts per minute was normalized to the first imaging time point on Day 1.
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Timepoint [4]
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7 weeks
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Secondary outcome [5]
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Number of Patients With 124I-cG250 Tumor Uptake After the First and Fifth Infusions of 124I-cG250.
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Assessment method [5]
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PET imaging studies were performed at 1 - 4 hours post infusion, and at two other time points over the ensuing one-week period.
Quantitative uptakes of 124I-cG250 were assessed in one selected reference tumour lesion identified by 18F-FDG-PET imaging. Tumour volume of Interest (VOI) was delineated around the whole tumour mass on the consecutive transverse slices of FDG-PET/CT images at which the tumours were most clearly identified.
Uptakes of 124I-cG250 were assessed in one selected reference tumour lesion identified by 18F-FDG-PET imaging.
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Timepoint [5]
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7 weeks
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Secondary outcome [6]
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Serum Pharmacokinetics as Measured by Mean Initial Half-life (T½ a) and Mean Terminal Half-life (T½ ß) After the First and Fifth Infusions of 124I-cG250 as Measured by Blood 124I Radioactivity and After the First Dose as Measured by ELISA.
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Assessment method [6]
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Blood samples were taken prior to 124I-cG250 infusion and 5 minutes, 1, 2, 4 and 24 hours post 124I-cG250 infusion. The pharmacokinetics of 124I-cG250 were calculated using gamma scintillation counting and by enzyme-linked immunosorbent assay (ELISA).
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Timepoint [6]
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7 weeks
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Secondary outcome [7]
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Serum Pharmacokinetics as Measured by Mean Volume of Central Compartment (V1) After the First and Fifth Infusions of 124I-cG250 as Measured by Blood 124I Radioactivity and After the First Dose as Measured by ELISA.
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Assessment method [7]
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Blood samples were taken prior to 124I-cG250 infusion and 5 minutes, 1, 2, 4 and 24 hours post 124I-cG250 infusion. The pharmacokinetics of 124I-cG250 were calculated using gamma scintillation counting and by enzyme-linked immunosorbent assay (ELISA).
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Timepoint [7]
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7 weeks
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Secondary outcome [8]
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Serum Pharmacokinetics as Measured by Mean Area Under the Concentration Curve Extrapolated to Infinite Time (AUC) After the First and Fifth Infusions of 124I-cG250 as Measured by Blood 124I Radioactivity and After the First Dose as Measured by ELISA.
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Assessment method [8]
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Blood samples were taken prior to 124I-cG250 infusion and 5 minutes, 1, 2, 4 and 24 hours post 124I-cG250 infusion. The pharmacokinetics of 124I-cG250 were calculated using gamma scintillation counting and by enzyme-linked immunosorbent assay (ELISA).
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Timepoint [8]
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7 weeks
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Secondary outcome [9]
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Serum Pharmacokinetics as Measured by Mean Total Serum Clearance (CL) After the First and Fifth Infusions of 124I-cG250 as Measured by Blood 124I Radioactivity and After the First Dose as Measured by ELISA.
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Assessment method [9]
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Blood samples were taken prior to 124I-cG250 infusion and 5 minutes, 1, 2, 4 and 24 hours post 124I-cG250 infusion. The pharmacokinetics of 124I-cG250 were calculated using gamma scintillation counting and by enzyme-linked immunosorbent assay (ELISA).
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Timepoint [9]
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7 weeks
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Secondary outcome [10]
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Serum Pharmacokinetics as Measured by Mean Maximum Serum Concentration (Cmax) After the First and Fifth Infusions of 124I-cG250 as Measured by Blood 124I Radioactivity and After the First Dose as Measured by ELISA.
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Assessment method [10]
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Blood samples were taken prior to 124I-cG250 infusion and 5 minutes, 1, 2, 4 and 24 hours post 124I-cG250 infusion. The pharmacokinetics of 124I-cG250 were calculated using gamma scintillation counting and by enzyme-linked immunosorbent assay (ELISA).
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Timepoint [10]
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7 weeks
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Secondary outcome [11]
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Number of Patients With Decreases in Tumour Blood Flow on Week 3 Versus Baseline.
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Assessment method [11]
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15O-H2O PET scans were performed up to 14 days prior to treatment and between days 15-22 in the first treatment cycle only. Approximately 750 megabecquerel (MBq) of 15O-H2O were administered intravenously and data was acquired dynamically over 5-10 minutes. The PET scan field of view was of an anatomical region containing a least one reference tumour lesion. Quantitation of blood flow within tumour was performed, and expressed in mL/mg/min. Follow-up 15O-H2O PET scan quantitated blood flow within the same reference lesion(s), allowing direct comparison of any change in quantitative tumour blood flow in response to treatment to be measured.
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Timepoint [11]
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7 weeks
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Secondary outcome [12]
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Number of Patients With Human Anti-chimeric Antibodies (HACA)
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Assessment method [12]
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Blood samples (5 mL/sample) were drawn prior to each cG250 or 124I-cG250 infusion during cycle 1 and also at the End of Study visit. If a second cycle of treatment was administered, HACA was performed at the End of Study visit.
The immunochemical measurement of anti-cG250 antibodies in human serum was performed by an enzyme-linked immunosorbent assay (ELISA).
Samples with values greater than the limit of quantitation (16 ng/mL) were considered HACA positive. Samples at or below that level were reported as negative.
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Timepoint [12]
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7 - 14 weeks
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Eligibility
Key inclusion criteria
- Metastatic or unresectable Renal Cell Cancer (with clear cell component).
- Measurable disease by RECIST on CT with at least one measurable lesion 2 cm or greater
in diameter, which is deemed to be assessable by PET imaging.
- At least 4 weeks after chemotherapy, radiotherapy or immunotherapy (6 weeks for
nitrosourea drugs).
- Expected survival at least 3 months.
- Karnofsky performance status (KPS) of 70% or greater.
- Age 18 years or older.
- Vital laboratory parameters within normal, or protocol specified ranges.
- Left ventricular ejection fraction greater than 55% on GCBP scan.
- Systolic blood pressure =150mmHg and diastolic blood pressure =90mmHg.
- Able to give written informed consent.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Prior exposure to cG250 monoclonal antibody (exception: no circulating human
anti-chimeric antibody to cG250).
- Prior treatment with vascular endothelial growth factor (VEGF)-targeting agents (e.g.
bevacizumab) or multi-kinase inhibitors (e.g. sorafenib) not including sunitinib.
(Patients currently receiving sunitinib may be eligible if tolerating a stable dose of
sunitinib on a four week on / two week off regimen, with toxicity due to sunitinib =
CTCAE grade 2; and for whom the investigator deems it clinically reasonable to
withhold sunitinib for at least four weeks prior to commencement of study treatment.)
- Active central nervous system (CNS) metastases (exception: CNS metastases adequately
treated (surgery or radiotherapy) with no progression for at least three months).
- Known HIV positivity.
- Clinically significant heart disease.
- History of hypertension requiring hospitalisation.
- Other serious illnesses, eg, serious infections requiring antibiotics, bleeding
disorders.
- Major surgery or radiation therapy within 4 weeks prior to, or planned within 6 weeks
of starting the study treatment. (Prior palliative radiotherapy to metastatic
lesion(s) permitted, provided at least one measurable lesion was not irradiated or has
progressed following radiotherapy.)
- Severe haemorrhage within 4 weeks prior to starting the study treatment.
- Any of the following within the 12 months prior to study drug administration:
myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident or transient
ischemic attack, or pulmonary embolism.
- Pre-existing thyroid abnormality with unstable thyroid function despite medication.
- Ongoing moderate to severe cardiac dysrhythmias, any severity of atrial fibrillation,
or prolongation of the corrected QT interval (QTc) to greater than 450 millisecond for
males or 470 millisecond for females.
- Participation in a clinical trial involving another investigational agent within 4
weeks.
- Pregnancy or breastfeeding.
- Women of childbearing potential not using a medically acceptable means of
contraception.
- Psychiatric or addictive disorders that may compromise the ability to give informed
consent.
- Not available for follow-up assessment.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/02/2008
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/09/2012
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Sample size
Target
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Accrual to date
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Final
8
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Austin Health (Ludwig Institute Oncology Unit) - Heidelberg
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Recruitment postcode(s) [1]
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3084 - Heidelberg
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Funding & Sponsors
Primary sponsor type
Other
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Name
Ludwig Institute for Cancer Research
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Address
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Country
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Other collaborator category [1]
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Commercial sector/Industry
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Name [1]
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Pfizer
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Address [1]
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Country [1]
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Other collaborator category [2]
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Commercial sector/Industry
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Name [2]
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Heidelberg Pharma AG
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Address [2]
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Ethics approval
Ethics application status
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Summary
Brief summary
This clinical trial explores the safety, efficacy, and effects on functional imaging of cG250
monoclonal antibody (mAb) administered intravenously weekly in combination with daily oral
sunitinib, in patients with advanced renal cell carcinoma.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT00520533
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Trial related presentations / publications
Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, Pruim J, Price P. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999 Dec;35(13):1773-82. doi: 10.1016/s0959-8049(99)00229-4.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.
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Public notes
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Contacts
Principal investigator
Name
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A/Prof Ian D Davis, FRACP, FAChPM, MBBS, PhD
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Address
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Ludwig Institute for Cancer Research
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT00520533
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