Vaccine Therapy Before Surgery in Treating Patients With Localized Kidney Cancer

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02170389
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 5
• Location: 1
• Arm: 1
• Actual Duration (Months): 29.1
• Patients Per Site Per Month: 0.2

Study Details

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	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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
• 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: Oct 14, 2014
• Actual Primary Completion Date: Mar 17, 2017
• Actual Study Completion Date: Mar 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 Names: AGS-003

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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)

• Study Protocol and Statistical Analysis Plan - Mar 13, 2017

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT02170389
• Other Study ID Numbers: I 250113; NCI-2014-01254; AGS-003-012; I 250113; P30CA016056
• First Posted: Jun 23, 2014
• Last Update Posted: Jul 7, 2020
• Last Verified: Jul 1, 2020

• Additional relevant MeSH terms: Carcinoma, Renal Cell; Kidney Neoplasms

Study Results

Participant Flow

Arm/Group Title	Treatment (AGS-003 Immunotherapy, Nephrectomy)
Arm/Group Description	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
Period Title: Overall Study
STARTED	5
COMPLETED	4
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (AGS-003 Immunotherapy, Nephrectomy)
Arm/Group Description	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
Overall Participants	5
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.4 (19.4)
Sex: Female, Male (Count of Participants)
Female	1 20%
Male	4 80%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	5 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Immune Marker Expression (units on a scale) [Mean (Standard Deviation) ]

Outcome Measures

1. Primary Outcome

Title	Change in Immune Marker Expression Levels
Description	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

Outcome Measure Data

Analysis Population Description

The clinical trial was terminated due to lack of funding before data were collected.

Arm/Group Title	Treatment (AGS-003 Immunotherapy, Nephrectomy)
Arm/Group Description	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
Measure Participants	0

2. Secondary Outcome

Title	Adverse Event Rates as Graded by the Common Terminology Criteria for Adverse Events Version 4.0
Description	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

Outcome Measure Data

Analysis Population Description

Only patients who received any injections were included.

Arm/Group Title	Treatment (AGS-003 Immunotherapy, Nephrectomy)
Arm/Group Description	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
Measure Participants	4
Any Grade AE	100
Any Grade 1	100
Any Grade 2	50
Any Grade 3	25
Any Grade 4	0
Any Grade 5	0

Adverse Events

Time Frame	All deaths and new AEs occurring from the date of signed consent until 30-days after the administration of the last study treatment or a new treatment is started, are reported.
Arm/Group Title	Treatment (AGS-003 Immunotherapy, Nephrectomy)
Arm/Group Description	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
All Cause Mortality
	Treatment (AGS-003 Immunotherapy, Nephrectomy)
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Serious Adverse Events
	Treatment (AGS-003 Immunotherapy, Nephrectomy)
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (AGS-003 Immunotherapy, Nephrectomy)
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Cardiac disorders
Bundle branch block	1/4 (25%)	1
General disorders
Fatigue	1/4 (25%)	1
Inflammation	1/4 (25%)	2
Influenza like illness	1/4 (25%)	1
Injection site inflammation	1/4 (25%)	1
Injection site pain	1/4 (25%)	1
Injection site pruritus	1/4 (25%)	1
Injection site reaction	2/4 (50%)	2
Injection site swelling	1/4 (25%)	1
Infections and infestations
Nasopharyngitis	1/4 (25%)	2
Injury, poisoning and procedural complications
Procedural pain	1/4 (25%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/4 (25%)	1
Pain in extremity	1/4 (25%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/4 (25%)	1
Skin and subcutaneous tissue disorders
Rash	1/4 (25%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.