A Study of CNTO 328 in Subjects With Metastatic Renal Cell Carcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Centocor, Inc.
ClinicalTrials.gov Identifier:
NCT00265135
First received: December 13, 2005
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to better understand the safety, tolerability and distribution of CNTO 328 in the bloodstream.


Condition Intervention Phase
Carcinoma, Renal Cell
Drug: CNTO 328
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of a Chimeric Antibody Against Interleukin-6 (CNTO 328) in Subjects With Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Centocor, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Number of Patients With Tumor Response (Parts 2 and 3) [ Time Frame: Up to Week 11 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Pre dose, up to 6 weeks after the last dose ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events (Parts 1, 2, and 3) [ Time Frame: Up to 6 weeks after the last dose ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serum Antibodies to CNTO 328 (Parts 1, 2, and 3) [ Time Frame: Up to 6 weeks after the last dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 6 weeks after the last dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 6 weeks after the last dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Screening (3 weeks prior to first dose), Week 7, Week 11, and 6 weeks after the last dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Screening (3 weeks prior to first dose), Week 7, Week 11, and 6 weeks after the last dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Within 2 weeks before dose, prior to first dose, Days 29, 43, 57, and 71, and 6 weeks after the last dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Within 2 weeks before first dose, pre dose, post dose (6 weeks after the last dose) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Enrollment: 68
Study Start Date: August 2003
Study Completion Date: February 2006
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 (CNTO 328)
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.
Drug: CNTO 328
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.
Experimental: Part 2 (CNTO 328)
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.
Drug: CNTO 328
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.
Experimental: Part 3 (CNTO 328)
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.
Drug: CNTO 328
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00265135

Locations
Czech Republic
Brno, Czech Republic
Hradec Nad Svitavou, Czech Republic
France
Caen, France
Lyon Cedex 08, France
Montpellier, France
Montpellier Cedex 5 N/A, France
Villejuif N/A, France
Netherlands
Groningen, Netherlands
Nijmegen, Netherlands
Rotterdam, Netherlands
United Kingdom
Birmingham, United Kingdom
Leeds, United Kingdom
Manchester, United Kingdom
Plymouth, United Kingdom
Sponsors and Collaborators
Centocor, Inc.
Investigators
Study Director: Centocor, Inc. Clinical Trial Centocor, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Centocor, Inc.
ClinicalTrials.gov Identifier: NCT00265135     History of Changes
Other Study ID Numbers: CR005278, C0328T01
Study First Received: December 13, 2005
Last Updated: July 1, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Centocor, Inc.:
Renal cell carcinoma
CNTO 328
Infusions
Renal cell cancer

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

ClinicalTrials.gov processed this record on July 28, 2014