Trial Outcomes & Findings for Study of Safety and Functional Imaging of cG250 and Sunitinib in Patients With Advanced Renal Cell Carcinoma (NCT NCT00520533)

NCT ID: NCT00520533

Last Updated: 2022-10-12

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

8 participants

Primary outcome timeframe

up to 14 weeks

Results posted on

2022-10-12

Participant Flow

8 patients were recruited and signed informed consent; 2 patients were withdrawn prior to receiving study treatment. (One patient was withdrawn from the study because of requiring urgent radiotherapy and the other withdrew consent.)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.

Participant milestones

Participant milestones
Measure	cG250 + Sunitinib 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 Up to 2 cycles available on-study.
Overall Study STARTED	8
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	cG250 + Sunitinib 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 Up to 2 cycles available on-study.
Overall Study Death	1
Overall Study Suspension of the study for safety reasons	1
Overall Study Withdrawal by Subject	1
Overall Study Physician Decision	1

Baseline Characteristics

Study of Safety and Functional Imaging of cG250 and Sunitinib in Patients With Advanced Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	cG250 + Sunitinib n=6 Participants 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 Up to 2 cycles available on-study.
Age, Continuous	64.3 years STANDARD_DEVIATION 9.913 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Australia	6 participants n=5 Participants

PRIMARY outcome

Timeframe: up to 14 weeks

Population: All patients who received at least one dose of cG250.

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=6 Participants 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 Up to 2 cycles available on-study.
Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs), Dose Limiting Toxicities (DLTs) or Adverse Events Leading to Discontinuation. Number of Patients With at least 1 AE	6 Participants
Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs), Dose Limiting Toxicities (DLTs) or Adverse Events Leading to Discontinuation. Number of Patients With at Least 1 Serious AE	3 Participants
Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs), Dose Limiting Toxicities (DLTs) or Adverse Events Leading to Discontinuation. Number of Patients With a DLT	2 Participants
Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs), Dose Limiting Toxicities (DLTs) or Adverse Events Leading to Discontinuation. Number of Patients with an AE leading to treatment discontinuation	1 Participants

SECONDARY outcome

Timeframe: up to 14 weeks

Population: All patients who received at least one dose of cG250.and were evaluable for tumour response.

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).

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=4 Participants 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 Up to 2 cycles available on-study.
Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR)	0 Participants
Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Partial Response (PR)	1 Participants
Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Stable Disease (SD)	3 Participants
Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Progressive Disease (PD)	0 Participants

SECONDARY outcome

Timeframe: 7 weeks

Population: All patients who received at least one dose of cG250, completed cycle 1 and were evaluable for tumor metabolic response.

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.

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=4 Participants 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 Up to 2 cycles available on-study.
Number of Patients With Tumor Metabolic Response as Assessed by Serial 18F-FDG-PET Scans. CMR	1 Participants
Number of Patients With Tumor Metabolic Response as Assessed by Serial 18F-FDG-PET Scans. PMR	0 Participants
Number of Patients With Tumor Metabolic Response as Assessed by Serial 18F-FDG-PET Scans. SMD	3 Participants

SECONDARY outcome

Timeframe: 7 weeks

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.

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=6 Participants 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 Up to 2 cycles available on-study.
Whole Body Clearance as Measured by Mean Biological Half-life (T1/2) After the First and Fifth Infusions of 124I-cG250. Biological T1/2 Week 1	121.12 days Standard Deviation 20.68
Whole Body Clearance as Measured by Mean Biological Half-life (T1/2) After the First and Fifth Infusions of 124I-cG250. Biological T1/2 Week 5	149.12 days Standard Deviation 42.52

SECONDARY outcome

Timeframe: 7 weeks

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.

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=6 Participants 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 Up to 2 cycles available on-study.
Whole Body Clearance as Measured by Mean Effective Half-life (T1/2) After the First and Fifth Infusions of 124I-cG250. Effective T1/2 Week 1	54.46 hours Standard Deviation 5.00
Whole Body Clearance as Measured by Mean Effective Half-life (T1/2) After the First and Fifth Infusions of 124I-cG250. Effective T1/2 Week 5	59.15 hours Standard Deviation 6.40

SECONDARY outcome

Timeframe: 7 weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=6 Participants 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 Up to 2 cycles available on-study.
Number of Patients With 124I-cG250 Tumor Uptake After the First and Fifth Infusions of 124I-cG250. First Infusion · Tumor uptake	6 Participants
Number of Patients With 124I-cG250 Tumor Uptake After the First and Fifth Infusions of 124I-cG250. First Infusion · No Tumor uptake	0 Participants
Number of Patients With 124I-cG250 Tumor Uptake After the First and Fifth Infusions of 124I-cG250. Fifth Infusion · Tumor uptake	4 Participants
Number of Patients With 124I-cG250 Tumor Uptake After the First and Fifth Infusions of 124I-cG250. Fifth Infusion · No Tumor uptake	0 Participants

SECONDARY outcome

Timeframe: 7 weeks

Population: 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.

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).

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=6 Participants 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 Up to 2 cycles available on-study.
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. T½ α as measured by blood 124I radioactivity after the first infusion	9.83 hours Standard Deviation 8.63
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. T½ β as measured by blood 124I radioactivity after the first infusion	104.1 hours Standard Deviation 52.2
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. T½α as measured by ELISA after the first infusion	27.7 hours Standard Deviation 34.4
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. T½ β as measured by ELISA after the first infusion	105.2 hours Standard Deviation 52.2
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. T½ α as measured by blood 124I radioactivity after the fifth infusion	18.54 hours Standard Deviation 14.04
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. T½ β as measured by blood 124I radioactivity after the fifth infusion	146.9 hours Standard Deviation 69.2

SECONDARY outcome

Timeframe: 7 weeks

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=6 Participants 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 Up to 2 cycles available on-study.
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. V1 as measured by blood 124I radioactivity after the first infusion	3067 mL Standard Deviation 705
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. V1 as measured by blood 124I radioactivity after the fifith infusion	2542 mL Standard Deviation 267
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. V1 as measured by ELISA after the first infusion	2286 mL Standard Deviation 678

SECONDARY outcome

Timeframe: 7 weeks

Population: 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.

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=6 Participants 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 Up to 2 cycles available on-study.
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. AUC as measured by blood 124I radioactivity after the first infusion	520 hours*mcg/mL Standard Deviation 153
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. AUC as measured by blood 124I radioactivity after the fifth infusion	682 hours*mcg/mL Standard Deviation 240
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. AUC as measured by ELISA after the first infusion	759 hours*mcg/mL Standard Deviation 335

SECONDARY outcome

Timeframe: 7 weeks

Population: 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.

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=6 Participants 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 Up to 2 cycles available on-study.
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. CL as measured by blood 124I radioactivity after the first infusion	38.7 mL/hour Standard Deviation 19.7
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. CL as measured by blood 124I radioactivity after the fifth infusion	28.7 mL/hour Standard Deviation 15.7
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. CL as measured by ELISA after the first infusion	25.7 mL/hour Standard Deviation 17.5

SECONDARY outcome

Timeframe: 7 weeks

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=6 Participants 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 Up to 2 cycles available on-study.
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. Cmax as measured by blood 124I radioactivity after the first infusion	5.93 mcg/mL Standard Deviation 1.06
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. Cmax as measured by blood 124I radioactivity after the fifth infusion	6.661 mcg/mL Standard Deviation 0.678
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. Cmax as measured by ELISA after the first infusion	7.57 mcg/mL Standard Deviation 1.88

SECONDARY outcome

Timeframe: 7 weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=5 Participants 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 Up to 2 cycles available on-study.
Number of Patients With Decreases in Tumour Blood Flow on Week 3 Versus Baseline.	5 Participants

SECONDARY outcome

Timeframe: 7 - 14 weeks

Population: All patients who had one cG250 pre-treatment and at least one post-treatment sample taken.

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.

Outcome measures

Outcome measures
Measure	cG250 and Sunitinib n=6 Participants 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 Up to 2 cycles available on-study.
Number of Patients With Human Anti-chimeric Antibodies (HACA) Number of patients with positive HACA	0 Participants
Number of Patients With Human Anti-chimeric Antibodies (HACA) Number of patients with negative HACA	6 Participants

Adverse Events

cG250 + Sunitinib

Serious events: 3 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	cG250 + Sunitinib n=6 participants at risk 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 Up to 2 cycles available on-study.
Gastrointestinal disorders Vomiting	16.7% 1/6 • 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.
Cardiac disorders Cardiogenic shock	16.7% 1/6 • 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.
Respiratory, thoracic and mediastinal disorders Left pleural effusion	16.7% 1/6 • 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.

Other adverse events

Other adverse events
Measure	cG250 + Sunitinib n=6 participants at risk 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 Up to 2 cycles available on-study.
Blood and lymphatic system disorders Thrombocytopenia	33.3% 2/6 • 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.
Blood and lymphatic system disorders Anemia	16.7% 1/6 • 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.
Blood and lymphatic system disorders Neutropenia	16.7% 1/6 • 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.
Gastrointestinal disorders Nausea	66.7% 4/6 • 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.
Gastrointestinal disorders Stomatitis	50.0% 3/6 • 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.
Gastrointestinal disorders Diarrhea	33.3% 2/6 • 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.
Gastrointestinal disorders Dyspepsia	16.7% 1/6 • 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.
General disorders Fatigue	100.0% 6/6 • 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.
Infections and infestations Pharyngitis	16.7% 1/6 • 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.
Investigations Blood creatinine increased	16.7% 1/6 • 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.
Metabolism and nutrition disorders Anorexia	33.3% 2/6 • 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.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 1/6 • 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.
Musculoskeletal and connective tissue disorders Muscular weakness	16.7% 1/6 • 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.
Nervous system disorders Dysgeusia	16.7% 1/6 • 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.
Skin and subcutaneous tissue disorders Yellow skin	50.0% 3/6 • 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.
Skin and subcutaneous tissue disorders Skin discoloration	16.7% 1/6 • 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.
Skin and subcutaneous tissue disorders Dry skin	33.3% 2/6 • 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.
Skin and subcutaneous tissue disorders Erythema	16.7% 1/6 • 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.
Vascular disorders Hypertension	16.7% 1/6 • 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.
Cardiac disorders Ventricular ectopics	16.7% 1/6 • 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.
Ear and labyrinth disorders Vertigo	16.7% 1/6 • 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.
Eye disorders Hazy vision	16.7% 1/6 • 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.
Eye disorders Visual disturbance	16.7% 1/6 • 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.
Gastrointestinal disorders Vomiting	33.3% 2/6 • 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.
Skin and subcutaneous tissue disorders Facial swelling	16.7% 1/6 • 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.
Gastrointestinal disorders Loose Tooth	16.7% 1/6 • 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.
Gastrointestinal disorders Constipation	16.7% 1/6 • 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.
Infections and infestations Tooth abscess	16.7% 1/6 • 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.
Infections and infestations Urosepsis	16.7% 1/6 • 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.
Infections and infestations Oral candidiasis	16.7% 1/6 • 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.
Injury, poisoning and procedural complications Tenth rib fracture	16.7% 1/6 • 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.
Investigations GFR decreased	16.7% 1/6 • 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.
Musculoskeletal and connective tissue disorders Back pain	33.3% 2/6 • 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.
Musculoskeletal and connective tissue disorders Leg pain	16.7% 1/6 • 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.
Musculoskeletal and connective tissue disorders Flank pain	16.7% 1/6 • 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.
Musculoskeletal and connective tissue disorders Neck pain	16.7% 1/6 • 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.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	16.7% 1/6 • 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.
Nervous system disorders Dysphasia	16.7% 1/6 • 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.
Gastrointestinal disorders Heartburn	16.7% 1/6 • 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.
Psychiatric disorders Insomnia	33.3% 2/6 • 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.
Reproductive system and breast disorders Balanitis	16.7% 1/6 • 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.
Respiratory, thoracic and mediastinal disorders Dry cough	16.7% 1/6 • 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.
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 1/6 • 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.
Respiratory, thoracic and mediastinal disorders Hiccups	16.7% 1/6 • 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.
Respiratory, thoracic and mediastinal disorders Shortness of breath	16.7% 1/6 • 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.
Nervous system disorders Dizziness	16.7% 1/6 • 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.
Nervous system disorders Headache	16.7% 1/6 • 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.
Nervous system disorders Lightheadedness	16.7% 1/6 • 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.
Nervous system disorders Migraine	16.7% 1/6 • 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.
Nervous system disorders Tremor of hands	16.7% 1/6 • 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.

Additional Information

Jonathan Skipper PhD

Ludwig Institute for Cancer Research

Phone: 12124501539

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place