Study of IL2 in Combination With Zoledronic Acid in Patients With Kidney Cancer
Primary Purpose
Kidney Cancer
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IL2
Zoledronic acid
Sponsored by
About this trial
This is an interventional treatment trial for Kidney Cancer focused on measuring Renal Cell Cancer, Metastatic
Eligibility 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.
Sites / Locations
- University of Wisconsin
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
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.
Outcomes
Primary Outcome Measures
Number of Subjects With Antitumor Response With Low-dose Interleukin-2 in Combination With Zoledronic Acid
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
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
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
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.
Full Information
NCT ID
NCT00582790
First Posted
December 19, 2007
Last Updated
November 13, 2019
Sponsor
University of Wisconsin, Madison
Collaborators
Novartis
1. Study Identification
Unique Protocol Identification Number
NCT00582790
Brief Title
Study of IL2 in Combination With Zoledronic Acid in Patients With Kidney Cancer
Official Title
Phase II Study of Interleukin-2 in Combination With Zoledronic Acid in Patients With Untreated Metastatic Renal Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2013
Overall Recruitment Status
Terminated
Why Stopped
slow accrual
Study Start Date
August 2003 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
September 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
Novartis
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Cancer
Keywords
Renal Cell Cancer, Metastatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
IL2
Other Intervention Name(s)
Interleukin-2
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Zoledronic acid
Other Intervention Name(s)
Zometa
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Subjects With Antitumor Response With Low-dose Interleukin-2 in Combination With Zoledronic Acid
Description
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.
Time Frame
CT scans obtained at baseline, then every 2 cycles
Secondary Outcome Measure Information:
Title
Number of Participants With Overall Survival and Progression-free Survival at 24 Weeks
Description
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
Time Frame
Time frame is from study entry until time to disease progression and time to death, up to 50 months
Title
Number of Participants With Toxicities
Description
Patients were observed for toxicities. The National Cancer Institute Common Terminology Criteria Version 2.0 was used to categorize and report adverse events.
Time Frame
Baseline to 30 days after last dose of study treatment
Title
Number of Participants With Immunologic Responses
Description
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.
Time Frame
baseline to cycle 2 day 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Glenn Liu, MD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
12. IPD Sharing Statement
Links:
URL
https://cancer.wisc.edu/
Description
University of Wisconsin Carbone Cancer Center
Learn more about this trial
Study of IL2 in Combination With Zoledronic Acid in Patients With Kidney Cancer
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