Study of Safety and Effects of cG250 and Sunitinib in Patients With Advanced Renal Cell Carcinoma
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Purpose
This clinical trial explores the safety, efficacy, and effects on functional imaging of the combination of cG250 monoclonal antibody administered intravenously weekly in combination with daily oral sunitinib, in patients with advanced renal cell carcinoma.
| Condition | Intervention |
|---|---|
|
Renal Cell Carcinoma |
Biological: Chimeric monoclonal antibody cG250 Drug: Sunitinib malate |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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 |
- Safety and Tolerability of cG250 and sunitinib in patients with advanced RCC: Adverse events of cG250 administered concurrently with sunitinib [ Time Frame: 7 -13 weeks ] [ Designated as safety issue: Yes ]
- Tumour response assessed according to standard clinical criteria (RECIST) [ Time Frame: 7 - 13 weeks ] [ Designated as safety issue: No ]
- Presence of radioactivity in tumour and whole body, assessed by ¹²⁴I-cG250 PET imaging, serum levels of monoclonal antibody cG250 pharmacokinetics (¹²⁴I activity and ELISA) [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]
- Serum HACA assayed by ELISA [ Time Frame: 7 - 13 weeks ] [ Designated as safety issue: Yes ]
- Tumour glycolytic metabolism and tumour blood flow assessment by serial [18]F-FDG and [15]O-H₂O PET scans [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]
| Enrollment: | 6 |
| Study Start Date: | February 2008 |
| Study Completion Date: | September 2012 |
| Primary Completion Date: | July 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: On Study
Treatment (cycle 1):
Treatment (cycle 2 - investigator discretion):
|
Biological: Chimeric monoclonal antibody cG250
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. Other Name: Sutent
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| Australia, Victoria | |
| Austin Health (Ludwig Institute Oncology Unit) | |
| Heidelberg (Melbourne), Victoria, Australia, 3084 | |
| Principal Investigator: | A/Prof Ian D Davis, FRACP, FAChPM, MBBS, PhD | Ludwig Institute for Cancer Research |
More Information
No publications provided
| Responsible Party: | Linda Pan, Pharm.D. Assistant Director, Clinical Trials Management, Ludwig Institute for Cancer Research |
| ClinicalTrials.gov Identifier: | NCT00520533 History of Changes |
| Other Study ID Numbers: | LUD2007-004 |
| Study First Received: | August 22, 2007 |
| Last Updated: | February 27, 2013 |
| Health Authority: | Australia: Department of Health and Ageing Therapeutic Goods Administration |
Keywords provided by Ludwig Institute for Cancer Research:
|
Clinical trials cG250 mAb monoclonal antibody G250 sunitinib |
angiogenesis inhibitors Positron-Emission Tomography Pharmacokinetics Pharmacodynamics |
Additional relevant MeSH terms:
|
Carcinoma Carcinoma, Renal Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Kidney Diseases Urologic Diseases |
Antibodies Antibodies, Monoclonal Angiogenesis Inhibitors Sunitinib Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Angiogenesis Modulating Agents Growth Substances Growth Inhibitors Antineoplastic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 16, 2013