Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Angiogenesis Inhibitors

Immunoglobulins

Sunitinib

Immunologic Factors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

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

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.

Chimeric monoclonal antibody cG250

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.

Sunitinib malate

A/Prof Ian D Davis, FRACP, FAChPM, MBBS, PhD

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.

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

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

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.

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).

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.

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.

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.

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.

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).

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.

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.

Pfizer

Heidelberg Pharma AG

Ludwig Institute for Cancer Research

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.

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.

cG250 + Sunitinib

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Australia

Region of Enrollment

All patients who received at least one dose of cG250.

Jonathan Skipper PhD

Number of Patients With at least 1 AE

Number of Patients With at Least 1 Serious AE

Number of Patients With a DLT

Number of Patients with an AE leading to treatment discontinuation

cG250 and Sunitinib

Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs), Dose Limiting Toxicities (DLTs) or Adverse Events Leading to Discontinuation.

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

Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST).

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

Number of Patients With Tumor Metabolic Response as Assessed by Serial 18F-FDG-PET Scans.

Comparison of Biological T1/2 at Week 1 and Week 5.

Biological T1/2 Week 1

Biological T1/2 Week 5

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.

Whole Body Clearance as Measured by Mean Biological Half-life (T1/2) After the First and Fifth Infusions of 124I-cG250.

Comparison of Effective T1/2 at Week 1 and Week 5.

Effective T1/2 Week 1

Effective T1/2 Week 5

Whole Body Clearance as Measured by Mean Effective Half-life (T1/2) After the First and Fifth Infusions of 124I-cG250.

First Infusion

Fifth Infusion

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.

Number of Patients With 124I-cG250 Tumor Uptake After the First and Fifth Infusions of 124I-cG250.

T½ α as measured by blood 124I radioactivity after the first infusion

T½ β as measured by blood 124I radioactivity after the first 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

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.

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.

V1 as measured by blood 124I radioactivity after the first infusion

V1 as measured by blood 124I radioactivity after the fifith infusion

V1 as measured by ELISA after the first infusion

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.

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.

AUC as measured by blood 124I radioactivity after the first infusion

AUC as measured by blood 124I radioactivity after the fifth infusion

AUC as measured by ELISA after the first infusion

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.

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.

CL as measured by blood 124I radioactivity after the first infusion

CL as measured by blood 124I radioactivity after the fifth infusion

CL as measured by ELISA after the first infusion

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.

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.

Cmax as measured by blood 124I radioactivity after the first infusion

Cmax as measured by blood 124I radioactivity after the fifth infusion

Cmax as measured by ELISA after the first infusion

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.

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.

Number of Patients With Decreases in Tumour Blood Flow on Week 3 Versus Baseline.

Number of patients with positive HACA

Number of patients with negative HACA

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

Spots Global Cancer Trial Database for cg250 mab

Every month we try and update this database with for cg250 mab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cg250 mab

Every month we try and update this database with for cg250 mab cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cg250 mab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.