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

This study has been terminated.
(Closed prematurely due to toxicity)
Sponsor:
Collaborators:
Pfizer
Wilex
Information provided by:
Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:
NCT00520533
First received: August 22, 2007
Last updated: February 27, 2013
Last verified: February 2013
  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

Resource links provided by NLM:


Further study details as provided by Ludwig Institute for Cancer Research:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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):

  • cG250 10mg/m² IV weekly x5 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
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.

Drug: Sunitinib malate

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
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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00520533

Locations
Australia, Victoria
Austin Health (Ludwig Institute Oncology Unit)
Heidelberg (Melbourne), Victoria, Australia, 3084
Sponsors and Collaborators
Ludwig Institute for Cancer Research
Pfizer
Wilex
Investigators
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
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Antibodies
Antibodies, Monoclonal
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014