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
18 Years
N/A
Both
Renal Cell Carcinoma
Trial Information
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
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 and 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.
Patients with advanced kidney cancer who have never previously received cG250, sunitinib (or
similar drugs) may be eligible to participate in the study. A total of 14 patients are
expected to be recruited.
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 CT scan 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 ([18]F-FDG and [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.
Inclusion Criteria:
- Metastatic or unresectable Renal Cell Cancer (with clear cell component).
- Measurable disease by RECIST on CT with at least one measurable lesion 2 cm or
greater in diameter, which is deemed to be assessable by PET imaging.
- At least 4 weeks after chemotherapy, radiotherapy or immunotherapy (6 weeks for
nitrosourea drugs).
- Expected survival at least 3 months.
- Karnofsky performance status (KPS) of 70% or greater.
- Age 18 years or older.
- Vital laboratory parameters within normal, or protocol specified ranges.
- Left ventricular ejection fraction greater than 55% on GCBP scan.
- Systolic blood pressure ≤150mmHg and diastolic blood pressure ≤90mmHg
- Able to give written informed consent.
Exclusion Criteria:
- Prior exposure to cG250 monoclonal antibody (exception: no circulating human
anti-chimeric antibody to cG250).
- Prior treatment with VEGF-targeting agents (e.g. bevacizumab) or multi-kinase
inhibitors (e.g. sorafenib) not including sunitinib. (Patients currently receiving
sunitinib may be eligible if tolerating a stable dose of sunitinib on a four week on
/ two week off regimen, with toxicity due to sunitinib ≤ CTCAE grade 2; and for whom
the investigator deems it clinically reasonable to withhold sunitinib for at least
four weeks prior to commencement of study treatment.)
- Active central nervous system (CNS) metastases (exception: CNS metastases adequately
treated (surgery or radiotherapy) with no progression for at least three months).
- Known HIV positivity.
- Clinically significant heart disease.
- History of hypertension requiring hospitalisation.
- Other serious illnesses, eg, serious infections requiring antibiotics, bleeding
disorders.
- Major surgery or radiation therapy within 4 weeks prior to, or planned within 6 weeks
of starting the study treatment. (Prior palliative radiotherapy to metastatic
lesion(s) permitted, provided at least one measurable lesion was not irradiated or
has progressed following radiotherapy)
- Severe haemorrhage within 4 weeks prior to starting the study treatment.
- Any of the following within the 12 months prior to study drug administration:
myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident or transient
ischemic attack, or pulmonary embolism.
- Pre-existing thyroid abnormality with unstable thyroid function despite medication.
- Ongoing moderate to severe cardiac dysrhythmias, any severity of atrial fibrillation,
or prolongation of the QTc interval to greater than 450 msec for males or 470 msec
for females.
- Participation in a clinical trial involving another investigational agent within 4
weeks.
- Pregnancy or breastfeeding.
- Women of childbearing potential not using a medically acceptable means of
contraception.
- Psychiatric or addictive disorders that may compromise the ability to give informed
consent.
- Not available for follow-up assessment.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety and Tolerability of cG250 and sunitinib in patients with advanced RCC: Adverse events of cG250 administered concurrently with sunitinib
Outcome Time Frame:
7 -13 weeks
Safety Issue:
Yes
Principal Investigator
A/Prof Ian D Davis, FRACP, FAChPM, MBBS, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Ludwig Institute for Cancer Research
Authority:
Australia: Department of Health and Ageing Therapeutic Goods Administration
Study ID:
LUD2007-004
NCT ID:
NCT00520533
Start Date:
February 2008
Completion Date:
September 2012
Related Keywords:
- Renal Cell Carcinoma
- Clinical trials
- cG250 mAb
- monoclonal antibody G250
- sunitinib
- angiogenesis inhibitors
- Positron-Emission Tomography
- Pharmacokinetics
- Pharmacodynamics
- Carcinoma
- Carcinoma, Renal Cell
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