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

Renal Cell Carcinoma Clinical Trial

— ADAPT  

Official title:

An International Phase 3 Randomized Trial of Autologous Dendritic Cell Immunotherapy (AGS-003) Plus Standard Treatment of Advanced Renal Cell Carcinoma (ADAPT)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01582672
• Other study ID #: AGS-003-007
• Secondary ID: 2012-000871-17
• Status: Terminated
• Phase: Phase 3
• Start date: November 2012
• Est. completion date: April 2018

Study information

• Verified date: June 2017
• Source: Argos Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 462
• Est. completion date: April 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Renal Cell Carcinoma
• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma
• Renal Cell Carcinoma

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Argos Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Hungary,  Israel,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Duration from randomization to death	From date of subject randomization to date of death; assessed up to 42 months or until 290 deaths have been accrued on study
Secondary	Progression Free Survival		From date of subject randomization to date of progression; assessed up to 42 months
Secondary	Tumor Response	Monitor for evidence of the following tumor responses: Objective response rate, Duration of overall response, and Disease control rate.	From date of subject randomization to date of progression; assessed up to 42 months
Secondary	Monitor treatment emergent adverse events between both arms	Compare adverse events between both arms.	From safety baseline until either meeting a discontinuation criterion or death; assessed up to 42 months