Study of Safety and Functional Imaging of cG250 and Sunitinib in Patients With Advanced Renal Cell Carcinoma
Condition: Renal Cell Carcinoma (RCC)
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Chimeric monoclonal antibody cG250; Sunitinib malate
Intervention description: 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.; 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.
Intervention MeSH terms: Sunitinib; Antibodies; Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Clinical trials; cG250 mAb; monoclonal antibody (mAb) G250; sunitinib; angiogenesis inhibitors; Positron-Emission Tomography; Pharmacokinetics; Pharmacodynamics

Summary:

      This clinical trial explores the safety, efficacy, and effects on functional imaging of cG250
      monoclonal antibody (mAb) administered intravenously weekly in combination with daily oral
      sunitinib, in patients with advanced renal cell carcinoma.
    

Eligibility criteria:

        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 vascular endothelial growth factor (VEGF)-targeting agents (e.g.
             bevacizumab) or multi-kinase inhibitors (e.g. sorafenib) not including sunitinib.
             (Patients currently receiving sunitinib may be eligible if tolerating a stable dose of
             sunitinib on a four week on / two week off regimen, with toxicity due to sunitinib ≤
             CTCAE grade 2; and for whom the investigator deems it clinically reasonable to
             withhold sunitinib for at least four weeks prior to commencement of study treatment.)

          -  Active central nervous system (CNS) metastases (exception: CNS metastases adequately
             treated (surgery or radiotherapy) with no progression for at least three months).

          -  Known HIV positivity.

          -  Clinically significant heart disease.

          -  History of hypertension requiring hospitalisation.

          -  Other serious illnesses, eg, serious infections requiring antibiotics, bleeding
             disorders.

          -  Major surgery or radiation therapy within 4 weeks prior to, or planned within 6 weeks
             of starting the study treatment. (Prior palliative radiotherapy to metastatic
             lesion(s) permitted, provided at least one measurable lesion was not irradiated or has
             progressed following radiotherapy.)

          -  Severe haemorrhage within 4 weeks prior to starting the study treatment.

          -  Any of the following within the 12 months prior to study drug administration:
             myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
             graft, symptomatic congestive heart failure, cerebrovascular accident or transient
             ischemic attack, or pulmonary embolism.

          -  Pre-existing thyroid abnormality with unstable thyroid function despite medication.

          -  Ongoing moderate to severe cardiac dysrhythmias, any severity of atrial fibrillation,
             or prolongation of the corrected QT interval (QTc) to greater than 450 millisecond for
             males or 470 millisecond for females.

          -  Participation in a clinical trial involving another investigational agent within 4
             weeks.

          -  Pregnancy or breastfeeding.

          -  Women of childbearing potential not using a medically acceptable means of
             contraception.

          -  Psychiatric or addictive disorders that may compromise the ability to give informed
             consent.

          -  Not available for follow-up assessment.