Clinical trial NCT01582672: Phase 3 Trial of Autologous Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma
Official title: An International Phase 3 Randomized Trial of Autologous Dendritic Cell Immunotherapy (AGS-003) Plus Standard Treatment of Advanced Renal Cell Carcinoma (ADAPT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Advanced Renal Cell Carcinoma
Renal Cell Carcinoma
Metastatic Renal Cell Carcinoma
Keywords: RCC
Kidney Cancer
Lead sponsor: Argos Therapeutics
Sponsor class: INDUSTRY
First posted: 2012-04-23
Enrollment: 462
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a trial of AGS-003, which is being studied as a possible treatment for Advanced Renal Cell Carcinoma. The purpose of this study is to determine whether there is an overall survival (OS) benefit between subjects treated with AGS-003 in combination with standard treatment versus subjects treated with standard treatment alone.

Detailed description: This study will investigate the combination of an autologous ribonucleic acid (RNA) electroporated dendritic cell (DC) based immunotherapy, AGS-003, plus standard treatment (initiating with sunitinib). The primary objective in this study is to determine the median OS achieved by this combination compared to the OS resulting from use of active control (standard treatment), in a population of adults with advanced renal cell carcinoma (RCC), with nephrectomy indicated, and with remaining metastatic disease.

Eligibility criteria: Key Inclusion Criteria for Tumor Collection:

1. Diagnosis or clinical signs of advanced RCC
2. Scheduled for cytoreductive or partial nephrectomy

Key Exclusion Criteria for Tumor Collection:

1. Known inability to undergo sunitinib treatment as currently labeled, due to pre-existing medical conditions
2. Requirement for systemic chronic immunosuppressive drugs or corticosteroids
3. Evidence of brain metastases prior to nephrectomy

Key Inclusion Criteria for Treatment Study:

1. Advanced disease, histologically assessed as RCC, with predominantly clear cell histology
2. Metastatic disease (measurable or non-measurable) that can be monitored throughout the course of the study participation per RECIST 1.1
3. Subjects who are candidates for standard first-line therapy initiating with sunitinib
4. Time from diagnosis to treatment \< 1 year
5. Karnofsky performance status (KPS) ≥ 70%
6. Life expectancy of 6 months or greater
7. Resolution of all acute toxic effects of prior radiotherapy or surgical procedures to Grade ≤ 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
8. Adequate hematologic, renal, hepatic, and coagulation function
9. Negative serum pregnancy test for female subjects with reproductive potential, and agreement of all male and female subjects of reproductive potential to use a reliable form of contraception during the study and for 12 weeks after the last dose of study drug
10. Normal ECG or clinically non-significant finding(s) at Screening
11. Able to abstain from taking prohibited drugs, either prescription or non-prescription, during the treatment phase of the study
12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Key Exclusion Criteria for Treatment Study:

1. Prior systemic therapy (including adjuvant or neoadjuvant) of any kind for RCC, including immunotherapy, chemotherapy, hormonal, or investigational therapy
2. Prior history of malignancy within the preceding 3 years, except for adequately treated in situ carcinomas or non-melanoma skin cancer, adequately treated early stage breast cancer, superficial bladder cancer, and non-metastatic prostate cancer with a normal PSA
3. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of brain or leptomeningeal disease
4. Patients with 4 or more of the following risk factors:

   1. Hgb \< LLN
   2. Corrected calcium \> 10.0 mg/dL
   3. KPS \< 80%
   4. Neutrophils \> ULN
   5. Platelets \> ULN
5. Planned or elective surgical treatment post-nephrectomy for the direct management of RCC, within 28 days before Visit 1 (Week 0)
6. NCI CTCAE Grade 3 hemorrhage \< 28 days before Visit 1 (Day 0)
7. Clinically significant cardiovascular conditions within 3 months prior to Randomization
8. Significant gastrointestinal abnormalities
9. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
10. Active autoimmune disease or condition requiring chronic immunosuppressive therapy
11. Clinically significant infections, including human immunodeficiency virus, syphilis, and active hepatitis B or C
12. Current treatment with an investigational therapy on another clinical trial
13. Pregnancy or breastfeeding
14. Any serious medical condition or illness considered by the investigator to constitute an unwarranted high risk for investigational treatment

Primary outcomes:
measure: Overall Survival
timeFrame: From date of subject randomization to date of death; assessed up to 42 months or until 290 deaths have been accrued on study
Secondary outcomes:
measure: Progression Free Survival
timeFrame: From date of subject randomization to date of progression; assessed up to 42 months
measure: Tumor Response
timeFrame: From date of subject randomization to date of progression; assessed up to 42 months
measure: Monitor treatment emergent adverse events between both arms
timeFrame: From safety baseline until either meeting a discontinuation criterion or death; assessed up to 42 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Colorado Springs
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state: Colorado
city: Denver
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state: Colorado
city: Miami
country: United States
state: Florida
city: Tampa
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state: Florida
city: Atlanta
country: United States
state: Georgia
city: Augusta
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Meridian
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state: Idaho
city: Chicago
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state: Illinois
city: Maywood
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state: Illinois
city: Springfield
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state: Illinois
city: Greenwood
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state: Indiana
city: Indianapolis
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state: Indiana
city: Indianapolis
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state: Indiana
city: Iowa City
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state: Iowa
city: Kansas City
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state: Kansas
city: Wichita
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state: Kansas
city: Metairie
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state: Louisiana
city: New Orleans
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state: Louisiana
city: New Orleans
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state: Louisiana
city: Baltimore
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state: Maryland
city: Baltimore
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state: Massachusetts
city: Burlington
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state: Massachusetts
city: Detroit
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state: Michigan
city: Detroit
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state: Michigan
city: Grand Rapids
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state: Michigan
city: Lansing
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city: Minneapolis
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city: Rochester
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state: Minnesota
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state: Missouri
city: Omaha
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state: Nebraska
city: Omaha
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city: Omaha
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city: Lebanon
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state: New Hampshire
city: Hackensack
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state: New Jersey
city: Albuquerque
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state: New Mexico
city: Albany
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state: New York
city: East Syracuse
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city: New Hyde Park
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state: New York
city: New York
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city: New York
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state: New York
city: Stony Brook
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city: Syracuse
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state: New York
city: Charlotte
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state: North Carolina
city: Durham
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state: North Carolina
city: Raleigh
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state: North Carolina
city: Winston-Salem
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state: North Carolina
city: Cincinnati
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state: Ohio
city: Middletown
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city: Toledo
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city: Oklahoma City
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city: Portland
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state: Oregon
city: Portland
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state: Oregon
city: Springfield
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state: Oregon
city: Allentown
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state: Pennsylvania
city: Danville
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state: Pennsylvania
city: Easton
country: United States
state: Pennsylvania
city: Hershey
country: United States
state: Pennsylvania
city: Philadelphia
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state: Pennsylvania
city: Philadelphia
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state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: Charleston
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Myrtle Beach
country: United States
state: South Carolina
city: Sioux Falls
country: United States
state: South Dakota
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
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state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Charlottesville
country: United States
state: Virginia
city: Virginia Beach
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state: Virginia
city: Seattle
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state: Washington
city: Seattle
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state: Washington
city: Milwaukee
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state: Wisconsin
city: Milwaukee
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state: Wisconsin
city: Winnipeg
country: Canada
state: Manitoba
city: Hamilton
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Oshawa
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Greenfield Park
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Hradec Kralove
country: Czechia
city: Liberec
country: Czechia
city: Olomouc
country: Czechia
city: Prague
country: Czechia
city: Praha 8
country: Czechia
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Rehovot
country: Israel
city: Tel Hashomer
country: Israel
city: Zerifin
country: Israel
city: Roma
country: Italy
city: Rome
country: Italy
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Vigo
country: Spain
city: Cambridge
country: United Kingdom
city: Norwich
country: United Kingdom
city: Preston
country: United Kingdom
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Robert Figlin, MD, FACP
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Christopher G Wood, MD, FACP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Figlin RA, Tannir NM, Uzzo RG, Tykodi SS, Chen DYT, Master V, Kapoor A, Vaena D, Lowrance W, Bratslavsky G, DeBenedette M, Gamble A, Plachco A, Norris MS, Horvatinovich J, Tcherepanova IY, Nicolette CA, Wood CG; ADAPT study group. Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma. Clin Cancer Res. 2020 May 15;26(10):2327-2336. doi: 10.1158/1078-0432.CCR-19-2427. Epub 2020 Feb 7.