Kidney Cancer
Conditions
Keywords
Renal Cell Cancer, Metastatic
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.
Interventions
DRUGIL2
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.
DRUGZoledronic 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.
Sponsors
Novartis
University of Wisconsin, Madison
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Zoledronic Acid and Interleukin-2 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. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Rapid progression of disease | 1 |
Baseline characteristics
| Characteristic | Zoledronic Acid and Interleukin-2 |
|---|---|
| Age, Continuous | 56.2 Years STANDARD_DEVIATION 10.6 |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 2 / 11 |
Outcome results
Primary
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.
Time frame: CT scans obtained at baseline, then every 2 cycles
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| IL2 and Zoledronic Acid | Number of Subjects With Antitumor Response With Low-dose Interleukin-2 in Combination With Zoledronic Acid | 5 participants |
Secondary
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.
Time frame: baseline to cycle 2 day 8
Population: One patient did not receive study treatment and so was not included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IL2 and Zoledronic Acid | Number of Participants With Immunologic Responses | 0 participants |
Secondary
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
Time frame: Time frame is from study entry until time to disease progression and time to death, up to 50 months
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| IL2 and Zoledronic Acid | Number of Participants With Overall Survival and Progression-free Survival at 24 Weeks | 5 participants |
Secondary
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.
Time frame: Baseline to 30 days after last dose of study treatment
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| IL2 and Zoledronic Acid | Number of Participants With Toxicities | 11 participants |