Recurrent Renal Cell Carcinoma, Stage II Renal Cell Cancer, Stage I Renal Cell Cancer
Conditions
Brief summary
This pilot clinical trial studies vaccine therapy before surgery in treating patients with kidney cancer that has not spread to nearby lymph nodes or to other parts of the body. Vaccines made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells when they are infused back into the body.
Detailed description
PRIMARY OBJECTIVES: I. To assess the immune-modulatory systemic and intratumoral effects of AGS-003 (renal cell carcinoma/cluster of differentiation \[CD\]40L ribonucleic acid \[RNA\]-transfected autologous dendritic cell vaccine AGS-003) as neoadjuvant treatment in patients with localized renal cell carcinoma. SECONDARY OBJECTIVES: I. To assess the feasibility that total tumor RNA processing-related activities meet specifications for AGS-003 manufacturing utilizing a core needle biopsy procedure for tumor harvesting prior to nephrectomy. OUTLINE: Patients receive 3 injections of renal cell carcinoma/cluster of CD40L RNA-transfected autologous dendritic cell vaccine AGS-003 intradermally (ID) once every 7 days during weeks 6-8 in the absence of disease progression or unacceptable toxicity. Patients then undergo partial or radical nephrectomy on week 10. After completion of study treatment, patients are followed up at 1 month.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
PROCEDURENephrectomy
Undergo partial or radical nephrectomy
BIOLOGICALRenal Cell Carcinoma/CD40L RNA-Transfected Autologous Dendritic Cell Vaccine AGS-003
Given ID
Sponsors
National Cancer Institute (NCI)
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have localized non-metastatic renal cell carcinoma (RCC) (\< pT2, NO, MO), as per the American Joint Committee on Cancer (AJCC) seventh (7th) edition criteria * Must be surgical candidates as deemed fit by surgeon * Patients of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately * Willingness to undergo leukapheresis and biopsy procedures for the autologous components (peripheral blood mononuclear cells, plasma and fresh tumor specimen) required for manufacture of AGS-003 * Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
Exclusion criteria
* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (e.g., shortness of breath, fatigue, orthopnea, paroxysmal nocturnal dyspnea), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Radiation to primary tumor prior to enrollment in this study * Pregnant or nursing female patients * Unwilling or unable to follow protocol requirements * Active autoimmune disease or condition requiring chronic immunosuppressive therapy (e.g., rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, organ transplant recipient, etc.) * NOTE: abnormal laboratory values for autoimmunity markers in the absence of other signs/symptoms of autoimmune disease are not exclusionary * Known clinically significant infections, including human immunodeficiency virus (HIV) and active hepatitis B or C * Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive treatment (i.e., any significant medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the subject's risk by participating in this study) * Chronic use of systemic corticosteroids (i.e., \>= 10 mg/day prednisone or equivalent) * Received an investigational agent within 30 days prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Immune Marker Expression Levels | Baseline to up to 30 days post-nephrectomy | The time component will be modeled as a three-level classification factor. The full model for the effects of time will be fit using linear mixed model methods. The model will include a random patient effect and 5 fixed effects for time and the interactions. The presence of any time effect will be assessed with full-reduced model type 3 test. If the omnibus test is statistically significant at the p \< 0.05 level, then three pairwise time-point comparisons will be conducted. Expression measurements may be transformed to satisfy modeling assumptions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event Rates as Graded by the Common Terminology Criteria for Adverse Events Version 4.0 | Up to 30 days | Summarized in all patients who received AGS-003. These rates will be described as the proportion of patients with the event, by grade, and supported with exact 95% confidence intervals. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (AGS-003 Immunotherapy, Nephrectomy) Patients receive 3 injections of renal cell carcinoma/cluster of CD40L RNA-transfected autologous dendritic cell vaccine AGS-003 ID once every 7 days during weeks 6-8 in the absence of disease progression or unacceptable toxicity. Patients then undergo partial or radical nephrectomy on week 10.
Laboratory Biomarker Analysis: Correlative studies
Nephrectomy: Undergo partial or radical nephrectomy
Renal Cell Carcinoma/CD40L RNA-Transfected Autologous Dendritic Cell Vaccine AGS-003: Given ID | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study terminated prior to start of treat | 1 |
Baseline characteristics
| Characteristic | Treatment (AGS-003 Immunotherapy, Nephrectomy) | — |
|---|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 19.4 | — |
| Immune Marker Expression | — | — units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | — |
| Race (NIH/OMB) Asian | 0 Participants | — |
| Race (NIH/OMB) Black or African American | 0 Participants | — |
| Race (NIH/OMB) More than one race | 0 Participants | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | — |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | — |
| Race (NIH/OMB) White | 5 Participants | — |
| Sex: Female, Male Female | 1 Participants | — |
| Sex: Female, Male Male | 4 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Change in Immune Marker Expression Levels
The time component will be modeled as a three-level classification factor. The full model for the effects of time will be fit using linear mixed model methods. The model will include a random patient effect and 5 fixed effects for time and the interactions. The presence of any time effect will be assessed with full-reduced model type 3 test. If the omnibus test is statistically significant at the p \< 0.05 level, then three pairwise time-point comparisons will be conducted. Expression measurements may be transformed to satisfy modeling assumptions.
Time frame: Baseline to up to 30 days post-nephrectomy
Population: The clinical trial was terminated due to lack of funding before data were collected.
Secondary
Adverse Event Rates as Graded by the Common Terminology Criteria for Adverse Events Version 4.0
Summarized in all patients who received AGS-003. These rates will be described as the proportion of patients with the event, by grade, and supported with exact 95% confidence intervals.
Time frame: Up to 30 days
Population: Only patients who received any injections were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (AGS-003 Immunotherapy, Nephrectomy) | Adverse Event Rates as Graded by the Common Terminology Criteria for Adverse Events Version 4.0 | Any Grade AE | 100 percentage of subjects |
| Treatment (AGS-003 Immunotherapy, Nephrectomy) | Adverse Event Rates as Graded by the Common Terminology Criteria for Adverse Events Version 4.0 | Any Grade 1 | 100 percentage of subjects |
| Treatment (AGS-003 Immunotherapy, Nephrectomy) | Adverse Event Rates as Graded by the Common Terminology Criteria for Adverse Events Version 4.0 | Any Grade 2 | 50 percentage of subjects |
| Treatment (AGS-003 Immunotherapy, Nephrectomy) | Adverse Event Rates as Graded by the Common Terminology Criteria for Adverse Events Version 4.0 | Any Grade 3 | 25 percentage of subjects |
| Treatment (AGS-003 Immunotherapy, Nephrectomy) | Adverse Event Rates as Graded by the Common Terminology Criteria for Adverse Events Version 4.0 | Any Grade 4 | 0 percentage of subjects |
| Treatment (AGS-003 Immunotherapy, Nephrectomy) | Adverse Event Rates as Graded by the Common Terminology Criteria for Adverse Events Version 4.0 | Any Grade 5 | 0 percentage of subjects |