Vaccine Therapy Before Surgery in Treating Patients With Localized Kidney Cancer

• ClinicalTrials.gov Identifier: NCT02170389
• Recruitment Status: Terminated
• First Posted: June 23, 2014
• Results First Posted: January 6, 2020
• Last Update Posted: July 7, 2020
• Sponsor: Roswell Park Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Roswell Park Cancer Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Recurrent Renal Cell Carcinoma; Stage I Renal Cell Cancer; Stage II Renal Cell Cancer	Other: Laboratory Biomarker Analysis; Procedure: Nephrectomy; Biological: Renal Cell Carcinoma/CD40L RNA-Transfected Autologous Dendritic Cell Vaccine AGS-003	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Neoadjuvant AGS-003 Immunotherapy in Patients With Localized Kidney Cancer <pT2
• Actual Study Start Date: October 14, 2014
• Actual Primary Completion Date: March 17, 2017
• Actual Study Completion Date: March 17, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Nephrectomy; Undergo partial or radical nephrectomy; Biological: Renal Cell Carcinoma/CD40L RNA-Transfected Autologous Dendritic Cell Vaccine AGS-003; Given ID; Other Name: AGS-003

Outcome Measures

Primary Outcome Measures :

1. Change in Immune Marker Expression Levels [ Time Frame: 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 Outcome Measures :

1. Adverse Event Rates as Graded by the Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

Sponsors and Collaborators

Roswell Park Cancer Institute

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Dr. med.Thomas Schwaab, MD; Roswell Park Cancer Institute

  Study Documents (Full-Text)

Documents provided by Roswell Park Cancer Institute:

Study Protocol and Statistical Analysis Plan  [PDF] March 13, 2017

More Information

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT02170389
• Other Study ID Numbers: I 250113; NCI-2014-01254 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); AGS-003-012; I 250113 ( Other Identifier: Roswell Park Cancer Institute ); P30CA016056 ( U.S. NIH Grant/Contract )
• First Posted: June 23, 2014
• Results First Posted: January 6, 2020
• Last Update Posted: July 7, 2020
• Last Verified: July 2020

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