Back to resultsA Study of CNTO 328 in Subjects With Metastatic Renal Cell Carcinoma
Primary Purpose
Carcinoma, Renal Cell
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CNTO 328
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Renal Cell focused on measuring Renal cell carcinoma, CNTO 328, Infusions, Renal cell cancer
Eligibility Criteria
Inclusion Criteria: Clinical diagnosis (histologically confirmed, preferably) of metastatic renal cell carcinoma with documented metastases beyond the level of the regional lymphatics (ie, any T, any N, M1 disease) Measurable or evaluable disease (Part 1); measurable disease (Part 2 and Part 3) Documented disease progression based on objective tumor assessment (Part 2 and Part 3), proven by tumor measurements on 2 computerized tomography scans within 6 months prior to enrollment Life expectancy greater than or equal to 6 months at screening Serum C-reactive protein (CRP): detectable ( 4 mg/L or more) according to the standard assay of the core laboratory (Part 1 and Part 2); serum CRP detectable to 30 mg/L or more (Part 3) Exclusion Criteria: Received any investigational drug within 30 days, whichever is longer History of receiving murine or chimeric proteins or human/murine recombination products (such as BE8 and other anti-IL-6 monoclonal antibodies) Serious concurrent illness or significant cardiac disease characterized by significant ischemic coronary disease or congestive heart failure Chronic infection, prior history of recurrent infection, or clinically important active infection Presence of a transplanted solid organ (with the exception of a corneal transplant more than 3 months prior to screening) or having received an allogeneic bone marrow transplant or peripheral blood stem cell transplant
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Part 1 (CNTO 328)
Part 2 (CNTO 328)
Part 3 (CNTO 328)
Arm Description
In Part 1 of the study, 4 intravenous infusions (IV) [injection of a substance into a vein] of CNTO 328 will be administered to patients in 4 dose levels ranging from 1, 3, 6, and 12 mg/kg on days 1, 29, 43, and 57 to determine the maximum tolerated dose for Part 2 of the study.
In Part 2 of the study, 2 well tolerated dose levels of CNTO 328 from Part 1 of the study will be administered every 3 weeks as 4 IV infusions to patients.
In Part 3 of the study, CNTO 328 at a dose level of 6 mg/kg will be administered as IV infusion every 2 weeks for at least 6 doses.
Outcomes
Primary Outcome Measures
Number of Patients With Dose-limiting Toxicity as a Measure of Safety (Parts 1 and 3)
Number of Patients With Tumor Response (Parts 2 and 3)
Tumor response will be evaluated as sum of complete response (CR) and partial response (PR). CR is disappearance of all measurable and evaluable disease. No new lesions. No evidence of non evaluable disease. PR is 50% or more decrease from baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.
Serum Concentration of CNTO 328 (Parts 1, 2, and 3)
Number of Participants With Adverse Events (Parts 1, 2, and 3)
Change From Baseline in C-reactive Protein (Part 1)
Change From Baseline in Interleukin-6 levels (Part 1)
Secondary Outcome Measures
Serum Antibodies to CNTO 328 (Parts 1, 2, and 3)
Serum levels of antibodies to CNTO 328 will be used to evaluate potential immunogenicity.
Number of Patients With Clinical Benefit (Parts 1, 2, and 3)
Clinical benefit will include assessment of pain (measured using Brief Pain Inventory which includes 4 items assessing pain intensity (pain intensity subscales) and 7 items assessing how much pain has interfered with daily activities (pain interference subscales). The pain intensity score is assessed with 4 questions rated on 11-point numerical rating scale (NRS) ranging from "0 = no pain" to "10 = higher severity of pain". The pain interference score is assessed with 7 questions rated on 11-point numerical rating scale (NRS) ranging from "0 = does not interfere" to "10 = completely interferes". Higher scores indicate worsening), functional impairment (assessed using Karnofsky performance status which quantifies patient's well-being and activities of daily life), weight change (assessed by change in body weight).
Time to disease progression (Parts 2 and 3)
Disease progression is defines as greater than or equal to 25% increase in the sum of products of measurable lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or reappearance of any lesion which had disappeared, or appearance of any new lesion, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Duration of Tumor Response (Parts 2 and 3)
Duration of tumor response is defined as sum of complete response which is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of nonevaluable disease and partial response which is 50% or more decrease from baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.
Number of Patients With an Overall Tumor Response (Parts 2 and 3)
Overall tumor response is defined as sum of overall CR which is 2 or more objective responses of CR (complete disappearance of all measurable and evaluable disease.) documented for a minimum of 4 weeks apart, overall PR which is 2 or more objective responses of PR (50% or more decrease from baseline in the sum of products of perpendicular diameters of all measurable lesions.) or better documented for a minimum of 4 weeks apart, and overall stable disease which is at least 1 objective response of SD (radiologic assessments have been evaluated and does not qualify for CR, PR, or progressive disease) at least 3 weeks after baseline.
Change From Baseline in Quality of Life Measured Using Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue questionnaire (Parts 1, 2, and 3)
FACIT - Fatigue scale is a questionnaire to assess fatigue. It is a 13-item questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. Responded to each area are scored from 0 (not at all) to 4 (very much). Higher scores indicate worsening.
Change From Baseline in C-reactive Protein (Parts 2 and 3)
Change From Baseline in Interleukin-6 levels (Parts 2 and 3)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00265135
Brief Title
A Study of CNTO 328 in Subjects With Metastatic Renal Cell Carcinoma
Official Title
A Phase I/II Study of a Chimeric Antibody Against Interleukin-6 (CNTO 328) in Subjects With Metastatic Renal Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
August 2003 (undefined)
Primary Completion Date
February 2006 (Actual)
Study Completion Date
February 2006 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centocor, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to better understand the safety, tolerability and distribution of CNTO 328 in the bloodstream.
Detailed Description
This research study uses a type of drug called anti-IL-6 monoclonal antibody, also known as CNTO 328. CNTO 328 is a new experimental drug. This study is trying to better understand the safety, the tolerability (side effects), and the distribution of the drug in the blood stream. The effects of CNTO 328 in patients with renal cell carcinoma are currently unknown. However, recent data has shown that treatment with another anti-IL-6 monoclonal antibody reduces the symptoms of renal cell carcinoma.
The study is divided in 3 parts. Part 1 is the phase I portion of the study and evaluated the safety of CNTO 328 in subjects with metastatic renal cell carcinoma. Part 2 and 3 will evaluate efficacy and safety of the drug in this patient population.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Renal Cell
Keywords
Renal cell carcinoma, CNTO 328, Infusions, Renal cell cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
68 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1 (CNTO 328)
Arm Type
Experimental
Arm Description
In Part 1 of the study, 4 intravenous infusions (IV) [injection of a substance into a vein] of CNTO 328 will be administered to patients in 4 dose levels ranging from 1, 3, 6, and 12 mg/kg on days 1, 29, 43, and 57 to determine the maximum tolerated dose for Part 2 of the study.
Arm Title
Part 2 (CNTO 328)
Arm Type
Experimental
Arm Description
In Part 2 of the study, 2 well tolerated dose levels of CNTO 328 from Part 1 of the study will be administered every 3 weeks as 4 IV infusions to patients.
Arm Title
Part 3 (CNTO 328)
Arm Type
Experimental
Arm Description
In Part 3 of the study, CNTO 328 at a dose level of 6 mg/kg will be administered as IV infusion every 2 weeks for at least 6 doses.
Intervention Type
Drug
Intervention Name(s)
CNTO 328
Intervention Description
Patients will receive CNTO 328 at dose levels ranging from 1, 3, 6, and 12 mg/kg in Part 1 of the study to determine the maximum tolerated dose for Part 2 of the study. Patients will receive 2 well tolerated dose levels of CNTO 328 from Part 1 of the study every 3 weeks in Part 2 of the study. Patients will receive 6 mg/kg of CNTO 328 every 2 weeks in Part 3 of the study.
Primary Outcome Measure Information:
Title
Number of Patients With Dose-limiting Toxicity as a Measure of Safety (Parts 1 and 3)
Time Frame
Up to 6 weeks after the last dose
Title
Number of Patients With Tumor Response (Parts 2 and 3)
Description
Tumor response will be evaluated as sum of complete response (CR) and partial response (PR). CR is disappearance of all measurable and evaluable disease. No new lesions. No evidence of non evaluable disease. PR is 50% or more decrease from baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.
Time Frame
Up to Week 11
Title
Serum Concentration of CNTO 328 (Parts 1, 2, and 3)
Time Frame
Pre dose, up to 6 weeks after the last dose
Title
Number of Participants With Adverse Events (Parts 1, 2, and 3)
Time Frame
Up to 6 weeks after the last dose
Title
Change From Baseline in C-reactive Protein (Part 1)
Time Frame
Within 2 weeks before first dose, pre dose, post dose (6 weeks after the last dose)
Title
Change From Baseline in Interleukin-6 levels (Part 1)
Time Frame
Within 2 weeks before first dose, pre dose, post dose (6 weeks after the last dose)
Secondary Outcome Measure Information:
Title
Serum Antibodies to CNTO 328 (Parts 1, 2, and 3)
Description
Serum levels of antibodies to CNTO 328 will be used to evaluate potential immunogenicity.
Time Frame
Up to 6 weeks after the last dose
Title
Number of Patients With Clinical Benefit (Parts 1, 2, and 3)
Description
Clinical benefit will include assessment of pain (measured using Brief Pain Inventory which includes 4 items assessing pain intensity (pain intensity subscales) and 7 items assessing how much pain has interfered with daily activities (pain interference subscales). The pain intensity score is assessed with 4 questions rated on 11-point numerical rating scale (NRS) ranging from "0 = no pain" to "10 = higher severity of pain". The pain interference score is assessed with 7 questions rated on 11-point numerical rating scale (NRS) ranging from "0 = does not interfere" to "10 = completely interferes". Higher scores indicate worsening), functional impairment (assessed using Karnofsky performance status which quantifies patient's well-being and activities of daily life), weight change (assessed by change in body weight).
Time Frame
Up to 6 weeks after the last dose
Title
Time to disease progression (Parts 2 and 3)
Description
Disease progression is defines as greater than or equal to 25% increase in the sum of products of measurable lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or reappearance of any lesion which had disappeared, or appearance of any new lesion, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Time Frame
Up to 6 weeks after the last dose
Title
Duration of Tumor Response (Parts 2 and 3)
Description
Duration of tumor response is defined as sum of complete response which is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of nonevaluable disease and partial response which is 50% or more decrease from baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.
Time Frame
Screening (3 weeks prior to first dose), Week 7, Week 11, and 6 weeks after the last dose
Title
Number of Patients With an Overall Tumor Response (Parts 2 and 3)
Description
Overall tumor response is defined as sum of overall CR which is 2 or more objective responses of CR (complete disappearance of all measurable and evaluable disease.) documented for a minimum of 4 weeks apart, overall PR which is 2 or more objective responses of PR (50% or more decrease from baseline in the sum of products of perpendicular diameters of all measurable lesions.) or better documented for a minimum of 4 weeks apart, and overall stable disease which is at least 1 objective response of SD (radiologic assessments have been evaluated and does not qualify for CR, PR, or progressive disease) at least 3 weeks after baseline.
Time Frame
Screening (3 weeks prior to first dose), Week 7, Week 11, and 6 weeks after the last dose
Title
Change From Baseline in Quality of Life Measured Using Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue questionnaire (Parts 1, 2, and 3)
Description
FACIT - Fatigue scale is a questionnaire to assess fatigue. It is a 13-item questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. Responded to each area are scored from 0 (not at all) to 4 (very much). Higher scores indicate worsening.
Time Frame
Within 2 weeks before dose, prior to first dose, Days 29, 43, 57, and 71, and 6 weeks after the last dose
Title
Change From Baseline in C-reactive Protein (Parts 2 and 3)
Time Frame
Within 2 weeks before first dose, pre dose, post dose (6 weeks after the last dose)
Title
Change From Baseline in Interleukin-6 levels (Parts 2 and 3)
Time Frame
Within 2 weeks before first dose, pre dose, post dose (6 weeks after the last dose)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis (histologically confirmed, preferably) of metastatic renal cell carcinoma with documented metastases beyond the level of the regional lymphatics (ie, any T, any N, M1 disease)
Measurable or evaluable disease (Part 1); measurable disease (Part 2 and Part 3)
Documented disease progression based on objective tumor assessment (Part 2 and Part 3), proven by tumor measurements on 2 computerized tomography scans within 6 months prior to enrollment
Life expectancy greater than or equal to 6 months at screening
Serum C-reactive protein (CRP): detectable ( 4 mg/L or more) according to the standard assay of the core laboratory (Part 1 and Part 2); serum CRP detectable to 30 mg/L or more (Part 3)
Exclusion Criteria:
Received any investigational drug within 30 days, whichever is longer
History of receiving murine or chimeric proteins or human/murine recombination products (such as BE8 and other anti-IL-6 monoclonal antibodies)
Serious concurrent illness or significant cardiac disease characterized by significant ischemic coronary disease or congestive heart failure
Chronic infection, prior history of recurrent infection, or clinically important active infection
Presence of a transplanted solid organ (with the exception of a corneal transplant more than 3 months prior to screening) or having received an allogeneic bone marrow transplant or peripheral blood stem cell transplant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Centocor, Inc. Clinical Trial
Organizational Affiliation
Centocor, Inc.
Official's Role
Study Director
Facility Information:
City
Brno
Country
Czech Republic
City
Hradec Nad Svitavou
Country
Czech Republic
City
Caen
Country
France
City
Lyon Cedex 08
Country
France
City
Montpellier Cedex 5 N/A
Country
France
City
Montpellier
Country
France
City
Villejuif N/A
Country
France
City
Groningen
Country
Netherlands
City
Nijmegen
Country
Netherlands
City
Rotterdam
Country
Netherlands
City
Birmingham
Country
United Kingdom
City
Leeds
Country
United Kingdom
City
Manchester
Country
United Kingdom
City
Plymouth
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=159&filename=CR005278_CSR.pdf
Description
A Phase 1/2 Study of a Chimeric Antibody Against Interleukin-6 (CNTO 328) in Subjects with Metastatic Renal Cell Carcinoma
Learn more about this trial
A Study of CNTO 328 in Subjects With Metastatic Renal Cell Carcinoma
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