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Study of IL2 in Combination With Zoledronic Acid in Patients With Kidney Cancer

This study has been terminated.
(slow accrual)
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT00582790
First received: December 19, 2007
Last updated: March 18, 2013
Last verified: March 2013
History of Changes
  Purpose

This study is being done to see if we can improve the response of Interleukin-2 by adding Zoledronic acid. The effectiveness of the combination of drugs in kidney cancer is unknown and will be investigated in this study. In particular, this study will evaluate the effect of this combination on kidney cancer and will also examine the safety and side effects of IL-2 with Zoledronic acid.


Condition Intervention Phase
Kidney Cancer
 Drug: IL2
Drug: Zoledronic acid
 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: Phase II Study of Interleukin-2 in Combination With Zoledronic Acid in Patients With Untreated Metastatic Renal Cell Carcinoma

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Number of Subjects With Antitumor Response With Low-dose Interleukin-2 in Combination With Zoledronic Acid [ Time Frame: CT scans obtained at baseline, then every 2 cycles ] [ Designated as safety issue: No ]
    Anti-tumor response was measured per RECIST criteria (V1.0) and assessed by chest/abdomen/pelvis CT: Complete Response (CR), disappearance of all target lessions; Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Response (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started.


Secondary Outcome Measures:
  • Number of Participants With Overall Survival and Progression-free Survival at 24 Weeks [ Time Frame: Time frame is from study entry until time to disease progression and time to death, up to 50 months ] [ Designated as safety issue: No ]
    All 12 patients were followed for survival until death. 8 participants who received more than one cycle of treatment and who were considered evaluable for response were followed until time to progression. Disease progression was determined by CT scans of the chest/abdomen/pelvis obtained every 2 cycles and based on RECIST version 1.0. Progression is defined using RECIST (V1.0) at least a 20% increase in the sum of the longest diameter (LD)of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions

  • Number of Participants With Toxicities [ Time Frame: Baseline to 30 days after last dose of study treatment ] [ Designated as safety issue: Yes ]
    Patients were observed for toxicities. The National Cancer Institute Common Terminology Criteria Version 2.0 was used to categorize and report adverse events.

  • Number of Participants With Immunologic Responses [ Time Frame: baseline to cycle 2 day 8 ] [ Designated as safety issue: No ]
    Blood was collected to analyze T-cell populations from all patients prior to treatment on day 1 of cycles 1 and 2, and days 4 and 8 of cycles 1 and 2. Changes in gamma delta T-cell population and CD3 T-cell populations were reported.


Enrollment: 12
Study Start Date: August 2003
Study Completion Date: September 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Interleukin-2 subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles in combination with Zoledronic acid IV on day 1 of every 4 week (28 days) cycle.
 Drug: IL2
Interleukin-2 will be given at a starting dose of 7 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles.
Other Name: Interleukin-2
Drug: Zoledronic acid
Zoledronic acid will be given on day 1 intravenously over 15 or 30 minutes starting at 400mcg. If no significant increase in gamma delta-T cell augmentation is seen, the dose of zoledronic acid will be increased in the subsequent cycle up to a maximum dose of 3mg.
Other Name: Zometa

Detailed Description:

The purpose of this research is to evaluate the antitumor response of low-dose Interleukin-2 in combination with Zoledronic acid on subjects with previously untreated, unresectable metastatic renal cell carcinoma. Also, the study will assess the tolerability, safety, pharmacodynamic effects, and immunologic effects of low-dose Interleukin-2 in combination with Zoledronic acid on angiogenesis inhibition and anti-metastatic potential by measuring serum/plasma angiogenic/metastatic factor levels and by quantitating changes in cytokine expression, antigen-specific T-cell immune responses, and peripheral gd T-cell frequency and function.

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed renal cell carcinoma with metastasis.
  • Must have measurable disease.
  • No prior cytokine, chemotherapy, hormonal, or other immuno-based therapies (including vaccine or cellular based) for their renal cancer is allowed. No prior use of bisphosphonates will be allowed. One prior experimental therapy will be permitted as long as > 4 weeks have passed since last drug administration.
  • ECOG performance status 0 or 1
  • Adequate cardiac function by history.
  • Pulse-oximetry > 92% on room air.

Exclusion Criteria:

  • Radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Known brain metastases
  • Any history of an autoimmune disease (ie. psoriasis, inflammatory bowel disease, etc) must receive clearance by the investigator before being permitted on study due to the potential worsening of those disorders from IL-
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.
  • History of myocardial infarction or hospitalization for congestive heart failure within 12 months of enrollment.
  • History of prior malignancy (except basal cell carcinoma resected with curative intent) unless resected or treated with curative intent and disease free for > 5 years.
  • Any history of seizures given increased seizure risk with IL-2.
  • Organ allograft (transplant) recipients will be excluded given absolute contraindication with IL-2 therapy.
  • Pregnant women are excluded
  • Patients on systemic steroids (oral or IV) will not be eligible for the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00582790

Locations
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
University of Wisconsin, Madison
Novartis
Investigators
Principal Investigator: Glenn Liu, MD University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00582790     History of Changes
Other Study ID Numbers: HSC 2003-170, CO03805
Study First Received: December 19, 2007
Results First Received: September 30, 2011
Last Updated: March 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Wisconsin, Madison:
Renal Cell Cancer
Metastatic

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Interleukin-2
 Zoledronic acid
Diphosphonates
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on May 23, 2013