Phase 3 Trial of Autologous Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma

Overview

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.

Full Title of Study: “An International Phase 3 Randomized Trial of Autologous Dendritic Cell Immunotherapy (AGS-003) Plus Standard Treatment of Advanced Renal Cell Carcinoma (ADAPT)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2018

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.

Interventions

  • Drug: Standard Treatment
    • Standard treatment for Renal Cell Carcinoma
  • Biological: AGS-003
    • Autologous Dendritic Cell product. Intradermal injections; 8 injections in the 1st year followed by quarterly boosters.

Arms, Groups and Cohorts

  • Experimental: AGS-003 + Standard Treatment
    • Subjects on this arm will receive standard treatment for Renal Cell Carcinoma. In addition, subjects will receive AGS-003.
  • Active Comparator: Standard Treatment
    • Subjects on this arm will receive standard treatment for Renal Cell Carcinoma.

Clinical Trial Outcome Measures

Primary Measures

  • Overall Survival
    • Time Frame: From date of subject randomization to date of death; assessed up to 42 months or until 290 deaths have been accrued on study
    • Duration from randomization to death

Secondary Measures

  • Progression Free Survival
    • Time Frame: From date of subject randomization to date of progression; assessed up to 42 months
  • Tumor Response
    • Time Frame: From date of subject randomization to date of progression; assessed up to 42 months
    • Monitor for evidence of the following tumor responses: Objective response rate, Duration of overall response, and Disease control rate.
  • Monitor treatment emergent adverse events between both arms
    • Time Frame: From safety baseline until either meeting a discontinuation criterion or death; assessed up to 42 months
    • Compare adverse events between both arms.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Argos Therapeutics
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Robert Figlin, MD, FACP, Principal Investigator, Cedars-Sinai Medical Center
    • Christopher G Wood, MD, FACP, Principal Investigator, M.D. Anderson Cancer Center

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