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

NCT00520533 | Terminated Phase 1 Results

• 1 other identifier: LUD2007-004
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Renal Cell Carcinoma (RCC)

Keywords

Clinical trials; cG250 mAb; monoclonal antibody (mAb) G250; sunitinib; angiogenesis inhibitors; Positron-Emission Tomography; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (1)

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

  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.

  up to 14 weeks

Secondary Outcomes (12)

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

  up to 14 weeks

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

  7 weeks

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

  7 weeks

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

  7 weeks

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

  7 weeks

Study Arms (1)

On Study

EXPERIMENTAL

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

Biological: Chimeric monoclonal antibody cG250; Drug: Sunitinib malate

Interventions

Chimeric monoclonal antibody cG250 BIOLOGICAL

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.

On Study

Sunitinib malate DRUG

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.

Also known as: Sutent

On Study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead
• Pfizer: collaborator
• Heidelberg Pharma AG: collaborator

Study Sites (1)

Austin Health (Ludwig Institute Oncology Unit)

Heidelberg, Victoria, 3084, Australia

Location

Related Publications (2)

• Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, Pruim J, Price P. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999 Dec;35(13):1773-82. doi: 10.1016/s0959-8049(99)00229-4.

  PMID: 10673991 BACKGROUND

• Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.

  PMID: 10655437 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell; Mycobacterium Infections, Nontuberculous

Interventions

G250 monoclonal antibody; Sunitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Jonathan Skipper PhD
• Organization: Ludwig Institute for Cancer Research

jskipper@lcr.org

12124501539

Study Officials

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

  Ludwig Institute for Cancer Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2007
• First Posted: August 24, 2007
• Study Start: February 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: September 1, 2012
• Last Updated: October 12, 2022
• Results First Posted: June 16, 2021

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)