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

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00582790
• Collaborator: Novartis (Industry)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 61
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer	Drug: IL2; Drug: Zoledronic acid	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Aug 1, 2003
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

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 Names: 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 Names: Zometa

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Antitumor Response With Low-dose Interleukin-2 in Combination With Zoledronic Acid [CT scans obtained at baseline, then every 2 cycles]

   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

1. Number of Participants With Overall Survival and Progression-free Survival at 24 Weeks [Time frame is from study entry until time to disease progression and time to death, up to 50 months]

   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

2. Number of Participants With Toxicities [Baseline to 30 days after last dose of study treatment]

   Patients were observed for toxicities. The National Cancer Institute Common Terminology Criteria Version 2.0 was used to categorize and report adverse events.

3. Number of Participants With Immunologic Responses [baseline to cycle 2 day 8]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Wisconsin Carbone Cancer Center

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT00582790
• Other Study ID Numbers: HSC 2003-170; CO03805; A534260; SMPH/MEDICINE/MEDICINE*H
• First Posted: Dec 28, 2007
• Last Update Posted: Nov 25, 2019
• Last Verified: Mar 1, 2013

• Keywords provided by University of Wisconsin, Madison: Renal Cell Cancer; Metastatic
• Additional relevant MeSH terms: Kidney Neoplasms; Carcinoma, Renal Cell; Zoledronic Acid; Interleukin-2

Study Results

Participant Flow

Recruitment Details	The study opened to accrual on 09/30/2003 and closed to accrual on 08/05/2008. Recruitment occured in a medical clinic.

Arm/Group Title	Zoledronic Acid and Interleukin-2
Arm/Group Description	Patients 1-6: Zometa at 4mg intravenously on day 1 of each 28-day cycle and IL-2 at a starting dose of 7 MU/m2/day by subcutaneous injection days 1-5, weekly in weeks 1 through 3 of each cycle. patients 7, 8 and 9: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles. The last patients: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles and dose escalation of zometa.
Period Title: Overall Study
STARTED	12
COMPLETED	11
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Zoledronic Acid and Interleukin-2
Arm/Group Description	Patients 1-6: Zometa at 4mg intravenously on day 1 of each 28-day cycle and IL-2 at a starting dose of 7 MU/m2/day by subcutaneous injection days 1-5, weekly in weeks 1 through 3 of each cycle. patients 7, 8 and 9: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles. The last patients: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles and dose escalation of zometa.
Overall Participants	12
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.2 (10.6)
Sex: Female, Male (Count of Participants)
Female	3 25%
Male	9 75%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Anti tumor response was measured in those patients who completed at least 1 cycle of study treatment 4 subjects did not complete 1 cycle of treatment.

Arm/Group Title	IL2 and Zoledronic Acid
Arm/Group Description	Patients 1-6: Zometa at 4mg intravenously on day 1 of each 28-day cycle and IL-2 at a starting dose of 7 MU/m2/day by subcutaneous injection days 1-5, weekly in weeks 1 through 3 of each cycle. patients 7, 8 and 9: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles. The last patients: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles and dose escalation of zometa.
Measure Participants	8
Number [participants]	5 41.7%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

8 of the 12 participants who received more than 1 cycle of therapy and were considered evaluable for time to progression. All 12 were evaluated for survival

Arm/Group Title	IL2 and Zoledronic Acid
Arm/Group Description	Patients 1-6: Zometa at 4mg intravenously on day 1 of each 28-day cycle and IL-2 at a starting dose of 7 MU/m2/day by subcutaneous injection days 1-5, weekly in weeks 1 through 3 of each cycle. patients 7, 8 and 9: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles. The last patients: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles and dose escalation of zometa.
Measure Participants	12
Number [participants]	5 41.7%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Patients who received at least one dose of study medication. One of the 12 patients never received study medication so only 11 were evaluable for toxicity

Arm/Group Title	IL2 and Zoledronic Acid
Arm/Group Description	Patients 1-6: Zometa at 4mg intravenously on day 1 of each 28-day cycle and IL-2 at a starting dose of 7 MU/m2/day by subcutaneous injection days 1-5, weekly in weeks 1 through 3 of each cycle. patients 7, 8 and 9: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles. The last patients: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles and dose escalation of zometa.
Measure Participants	11
Number [participants]	11 91.7%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

One patient did not receive study treatment and so was not included in the analysis.

Arm/Group Title	Low-dose IL2 and Zoledronic Acid
Arm/Group Description	Patients 1-6: Zometa at 4mg intravenously on day 1 of each 28-day cycle and IL-2 at a starting dose of 7 MU/m2/day by subcutaneous injection days 1-5, weekly in weeks 1 through 3 of each cycle. patients 7, 8 and 9: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles. The last patients: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles and dose escalation of zometa.
Measure Participants	11
Number [participants]	0 0%

Adverse Events

Time Frame	Study period: 2003 to 2006. Adverse events were collected from time of study treatment to 30 days post treatment.
Adverse Event Reporting Description	Adverse events listed are those with at least possibly related. All SAE's are reported regardless of whether or not they were felt related to study procedures.
Arm/Group Title	Zoledronic Acid and Interleukin-2
Arm/Group Description	Patients 1-6: Zometa at 4mg intravenously on day 1 of each 28-day cycle and IL-2 at a starting dose of 7 MU/m2/day by subcutaneous injection days 1-5, weekly in weeks 1 through 3 of each cycle. patients 7, 8 and 9: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles. The last patients: IL-2 at a dose of 1 MU/m2/day by subcutaneous injection days 1-5, on weeks 1 through 3, in four week (28 days) cycles and dose escalation of zometa.
All Cause Mortality
	Zoledronic Acid and Interleukin-2
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Zoledronic Acid and Interleukin-2
	Affected / at Risk (%)	# Events
Total	2/11 (18.2%)
Cardiac disorders
Myocardial Infarction	1/11 (9.1%)	1
Gastrointestinal disorders
Gastritis	1/11 (9.1%)	1
Renal and urinary disorders
Creatinine	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Zoledronic Acid and Interleukin-2
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Blood and lymphatic system disorders
Anemia	1/11 (9.1%)	1
Cardiac disorders
Hypotension	4/11 (36.4%)	5
Eye disorders
Dry Eye	1/11 (9.1%)	2
Gastrointestinal disorders
Nausea	9/11 (81.8%)	9
Vomitting	8/11 (72.7%)	8
Diarrhea	7/11 (63.6%)	7
Constipation	1/11 (9.1%)	1
Gastritis	1/11 (9.1%)	1
General disorders
Fatigue	6/11 (54.5%)	9
Chills	9/11 (81.8%)	9
Fever	7/11 (63.6%)	7
Non-Cardiac Chest	1/11 (9.1%)	4
Myalgias/Arthralgias	5/11 (45.5%)	8
Musculocskeletal	7/11 (63.6%)	7
injection site reaction	7/11 (63.6%)	7
Taste changes	2/11 (18.2%)	2
Thyroiditis	1/11 (9.1%)	1
Hepatobiliary disorders
SGPT (ALT)	4/11 (36.4%)	4
SGOT (AST)	4/11 (36.4%)	4
GGT	1/11 (9.1%)	1
Infections and infestations
Urinary Tract Infection	1/11 (9.1%)	1
Infection NOS	2/11 (18.2%)	2
Metabolism and nutrition disorders
Weight Loss	1/11 (9.1%)	1
Anorexia	5/11 (45.5%)	5
Hyponatremia	1/11 (9.1%)	1
Hyperglycemia	2/11 (18.2%)	2
Hypocalcemia	2/11 (18.2%)	4
Lipase	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Myalgias	5/11 (45.5%)	5
Arthralgias	4/11 (36.4%)	5
Bone pains	5/11 (45.5%)	5
Hand edema	2/11 (18.2%)	2
Nervous system disorders
Dizziness	1/11 (9.1%)	3
Headache	4/11 (36.4%)	4
Psychiatric disorders
Anxiety/Depression	2/11 (18.2%)	2
Renal and urinary disorders
Creatinine	2/11 (18.2%)	2
Urinary Frequency	2/11 (18.2%)	2
Respiratory, thoracic and mediastinal disorders
Cough	4/11 (36.4%)	4
Congestion	2/11 (18.2%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.