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Closed prematurely due to toxicity
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| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
| Heidelberg Pharma AG | INDUSTRY |
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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.
This study explores the safety, efficacy and effects on functional imaging of the combination of cG250 and sunitinib in patients with advanced renal cell carcinoma (kidney cancer).
When kidney cancer has spread beyond the kidney, it is usually not possible to cure it with surgery. Other treatments such as radiotherapy or chemotherapy are also of limited value. Kidney cancers often rely on certain proteins for their growth, particularly proteins that affect the ways that blood vessels grow into the cancer. Ingrowth of blood vessels supplies cancer cells with oxygen and nutrition; without the blood vessels, cancer deposits can not grow in size. When growth of the blood vessels is blocked, established cancers may stop growing or may shrink. This has been shown to work for some drugs that target this process in kidney cancers. One of these drugs is called sunitinib.
A protein, called G250, is also thought to be important in helping kidney cancers to grow. G250 is found on the cell surface of many kidney cancers. One possible method of interfering with the function of G250 is to target G250 with an antibody known as cG250. Clinical trials with cG250 have shown it to be safe, to home in on kidney cancer cells, and to persist in the blood and the cancer tissue for a long period of time.
The main purpose of this study is to explore whether the combination of sunitinib and cG250 is safe in patients with advanced kidney cancer. The study will also assess whether this combination is able to cause kidney cancer to shrink; will determine where cG250 travels within the body, whether the immune system reacts to the cG250 and whether sunitinib affects that; and whether the combination affects how kidney cancers grow or how blood flows within the tumour.
Eligible patients will receive cG250 10 mg/m² by weekly intravenous infusion for five weeks, followed by a two-week break (one cycle). The first and fifth dose will be trace-labeled with a radioactive substance (124I-cG250) detectable by a special scan called a Positron Emission Tomography (PET scan) to allow studies of the distribution of cG250. Sunitinib 50 mg by daily oral dose will also be given for 4 weeks (commencing on day 8 of the first treatment cycle), followed by a two-week break. Up to two cycles of treatment will be given. If a second cycle is given, cG250 will be given as four weekly doses and daily sunitinib will start on the same day. No 124I-cG250 will be administered after the first treatment cycle.
The extent of the kidney cancer will be assessed by Computed tomography (CT) at baseline and at the end of each treatment cycle. Safety assessments (physical examination, blood tests, gated cardiac blood pool scan, ECG-heart trace) will be performed at the beginning of each treatment cycle, repeated throughout the cycle and end of study. A number of blood tests and PET scans will be done in the first cycle to show how and in what amounts the 124I-cG250 distributes in the body. Other PET scans (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose {[18]F-FDG}) and 15O-water {[15]O-H2O}) will be performed to allow assessment of tumour growth and blood flow. Blood tests will also show whether the immune system recognises the infused cG250 by making an antibody against it.
A total of 14 patients were expected to be recruited; 8 were consented and 6 received study treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| On Study | Experimental | Treatment (cycle 1):
Treatment (cycle 2 - investigator discretion):
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Chimeric monoclonal antibody cG250 | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs), Dose Limiting Toxicities (DLTs) or Adverse Events Leading to Discontinuation. | 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. | up to 14 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). | 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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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| A/Prof Ian D Davis, FRACP, FAChPM, MBBS, PhD | Ludwig Institute for Cancer Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Austin Health (Ludwig Institute Oncology Unit) | Heidelberg | Victoria | 3084 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10673991 | Background | 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. | |
| 10655437 |
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8 patients were recruited and signed informed consent; 2 patients were withdrawn prior to receiving study treatment. (One patient was withdrawn from the study because of requiring urgent radiotherapy and the other withdrew consent.) Six patients were enrolled and received study treatment.
The study was terminated for safety reasons.
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| ID | Title | Description |
|---|---|---|
| FG000 | cG250 + Sunitinib | Treatment (cycle 1):
Treatment (cycle 2 - investigator discretion):
Up to 2 cycles available on-study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All patients who received at least one dose of cG250.
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| ID | Title | Description |
|---|---|---|
| BG000 | cG250 + Sunitinib | Treatment (cycle 1):
Treatment (cycle 2 - investigator discretion):
Up to 2 cycles available on-study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs), Dose Limiting Toxicities (DLTs) or Adverse Events Leading to Discontinuation. | 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. | All patients who received at least one dose of cG250. | Posted | Count of Participants | Participants | up to 14 weeks |
up to 14 weeks
Toxicity will be evaluated according to the National Cancer Institute CTCAE Scale (Version 3.0).
All events, which occurred after signed informed consent, but before first administration of study drug, were documented on the Pre-existing Signs and Symptom page. Thereafter, they were documented on the Adverse Event page.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | cG250 + Sunitinib | Treatment (cycle 1):
Treatment (cycle 2 - investigator discretion):
Up to 2 cycles available on-study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jonathan Skipper PhD | Ludwig Institute for Cancer Research | 12124501539 | jskipper@lcr.org |
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| ID | Term |
|---|---|
| D002292 | Carcinoma, Renal Cell |
| D009165 | Mycobacterium Infections, Nontuberculous |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C106533 | G250 monoclonal antibody |
| D000077210 | Sunitinib |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Sunitinib malate | Drug | 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. |
|
|
| up to 14 weeks |
| Number of Patients With Tumor Metabolic Response as Assessed by Serial 18F-FDG-PET Scans. | 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. | 7 weeks |
| Whole Body Clearance as Measured by Mean Biological Half-life (T1/2) After the First and Fifth Infusions of 124I-cG250. | 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. | 7 weeks |
| Whole Body Clearance as Measured by Mean Effective Half-life (T1/2) After the First and Fifth Infusions of 124I-cG250. | 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. | 7 weeks |
| Number of Patients With 124I-cG250 Tumor Uptake After the First and Fifth Infusions of 124I-cG250. | 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. | 7 weeks |
| Serum Pharmacokinetics as Measured by Mean Initial Half-life (T½ α) and Mean Terminal Half-life (T½ β) After the First and Fifth Infusions of 124I-cG250 as Measured by Blood 124I Radioactivity and After the First Dose as Measured by ELISA. | 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). | 7 weeks |
| 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. | 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). | 7 weeks |
| 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. | 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). | 7 weeks |
| 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. | 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). | 7 weeks |
| 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. | 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). | 7 weeks |
| Number of Patients With Decreases in Tumour Blood Flow on Week 3 Versus Baseline. | 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. | 7 weeks |
| Number of Patients With Human Anti-chimeric Antibodies (HACA) | 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. | 7 - 14 weeks |
| Background |
| 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. |
| Physician Decision |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | cG250 and Sunitinib | Treatment (cycle 1):
Treatment (cycle 2 - investigator discretion):
Up to 2 cycles available on-study. |
|
|
| Secondary | Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). | 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). | All patients who received at least one dose of cG250.and were evaluable for tumour response. | Posted | Count of Participants | Participants | up to 14 weeks |
|
|
|
| Secondary | Number of Patients With Tumor Metabolic Response as Assessed by Serial 18F-FDG-PET Scans. | 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. | All patients who received at least one dose of cG250, completed cycle 1 and were evaluable for tumor metabolic response. | Posted | Count of Participants | Participants | 7 weeks |
|
|
|
| Secondary | Whole Body Clearance as Measured by Mean Biological Half-life (T1/2) After the First and Fifth Infusions of 124I-cG250. | 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. | All patients who received the first and fifth infusion of 124I-cG250. Two patients received the first infusion but not the fifth infusion and as a result were not included in the Week 5 results. | Posted | Mean | Standard Deviation | days | 7 weeks |
|
|
|
|
| Secondary | Whole Body Clearance as Measured by Mean Effective Half-life (T1/2) After the First and Fifth Infusions of 124I-cG250. | 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. | All patients who received the first and fifth infusion of 124I-cG250. Two patients received the first infusion but not the fifth infusion and as a result were not included in the Week 5 results. | Posted | Mean | Standard Deviation | hours | 7 weeks |
|
|
|
|
| Secondary | Number of Patients With 124I-cG250 Tumor Uptake After the First and Fifth Infusions of 124I-cG250. | 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. | All patients who received the first and fifth infusion of 124I-cG250. Two patients received the first infusion but not the fifth infusion and as a result were not included in the tumour uptake after the fifth infusion of 124I-cG250. | Posted | Count of Participants | Participants | 7 weeks |
|
|
|
| Secondary | Serum Pharmacokinetics as Measured by Mean Initial Half-life (T½ α) and Mean Terminal Half-life (T½ β) After the First and Fifth Infusions of 124I-cG250 as Measured by Blood 124I Radioactivity and After the First Dose as Measured by ELISA. | 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). | All patients who received the first and fifth infusion of 124I-cG250. Two patients received the first infusion but not the fifth infusion and as a result were not included in the fifth infusion results. Two patients were not included in the T½ β ELISA analysis due to a disproportionate effect on the estimated parameter. | Posted | Mean | Standard Deviation | hours | 7 weeks |
|
|
|
| Secondary | 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. | 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). | All patients who received the first and fifth infusion of 124I-cG250. Two patients received the first infusion but not the fifth infusion and as a result were not included in the fifth infusion results. | Posted | Mean | Standard Deviation | mL | 7 weeks |
|
|
|
| Secondary | 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. | 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). | All patients who received the first and fifth infusion of 124I-cG250. Two patients received the first infusion but not the fifth infusion and as a result were not included the fifth infusion results. Two patients were not included in the ELISA analysis due to a disproportionate effect on the estimated parameter. | Posted | Mean | Standard Deviation | hours*mcg/mL | 7 weeks |
|
|
|
| Secondary | 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. | 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). | All patients who received the first and fifth infusion of 124I-cG250. Two patients received the first infusion but not the fifth infusion and as a result were not included in the fifth infusion results. Two patients were not included in the ELISA analysis due to a disproportionate effect on the estimated parameter. | Posted | Mean | Standard Deviation | mL/hour | 7 weeks |
|
|
|
| Secondary | 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. | 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). | All patients who received the first and fifth infusion of 124I-cG250. Two patients received the first infusion but not the fifth infusion and as a result were not included in the fifth infusion results. | Posted | Mean | Standard Deviation | mcg/mL | 7 weeks |
|
|
|
| Secondary | Number of Patients With Decreases in Tumour Blood Flow on Week 3 Versus Baseline. | 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. | Number of patients who received 15O-H2O PET scans at baseline and between days 15-22. One patient did not receive the 15O-H2O PET scans due to technical problems. | Posted | Count of Participants | Participants | 7 weeks |
|
|
|
| Secondary | Number of Patients With Human Anti-chimeric Antibodies (HACA) | 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. | All patients who had one cG250 pre-treatment and at least one post-treatment sample taken. | Posted | Count of Participants | Participants | 7 - 14 weeks |
|
|
|
| 1 |
| 6 |
| 3 |
| 6 |
| 6 |
| 6 |
| Cardiogenic shock | Cardiac disorders | MedDRA (12.0) | Systematic Assessment |
|
| Left pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Yellow skin | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Skin discoloration | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (12.0) | Systematic Assessment |
|
| Ventricular ectopics | Cardiac disorders | MedDRA (12.0) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hazy vision | Eye disorders | MedDRA (12.0) | Systematic Assessment |
|
| Visual disturbance | Eye disorders | MedDRA (12.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Facial swelling | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Loose Tooth | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Urosepsis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Tenth rib fracture | Injury, poisoning and procedural complications | MedDRA (12.0) | Systematic Assessment |
|
| GFR decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Leg pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dysphasia | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Heartburn | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
| Balanitis | Reproductive system and breast disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dry cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Shortness of breath | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Lightheadedness | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Tremor of hands | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
Not provided
Not provided
| D009369 | Neoplasms |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D007211 |
| Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Progressive Disease (PD) |
|
|
|
| Fifth Infusion |
|
|
|
| T½α as measured by ELISA after the first infusion |
|
|
| T½ β as measured by ELISA after the first infusion |
|
|
| T½ α as measured by blood 124I radioactivity after the fifth infusion |
|
|
| T½ β as measured by blood 124I radioactivity after the fifth infusion |
|
|
|
| V1 as measured by ELISA after the first infusion |
|
|
|
| AUC as measured by ELISA after the first infusion |
|
|
|
| CL as measured by ELISA after the first infusion |
|
|
|
| Cmax as measured by ELISA after the first infusion |
|
|