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A Safety and Feasibility Study of AGS-003-LNG for the Treatment of Stage 3 Non Small Cell Lung Cancer

Primary Purpose

Non-small Cell Lung Cancer (NSCLC)

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AGS-003-LNG
Carboplatin
Abraxane
Alimta
Cisplatin
Taxol
Radiation Therapy
Sponsored by
GU Research Network, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer (NSCLC) focused on measuring NSCLC, resectable, non-small cell lung cancer, immunotherapy, autologous, dendritic cell

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥ 19 years.
  2. Newly diagnosed non-small cell lung cancer indicated for routine lobectomy, mediastinoscopy, wedge resection, thoracotomy or Video-assisted thoracoscopic surgery (VATS) procedures with tumor collection.
  3. Stage III (T1-3, N1-2, M0) of any histology.
  4. Scheduled for routine lobectomy, mediastinoscopy, wedge resection, thoracotomy or VATS procedures.
  5. Signed and dated informed consent document for study participation.

After tumor collection, potential subjects must meet all the following criteria to be enrolled in study treatment:

  1. Successful RNA isolation and amplification from tumor sample (as determined by Argos).
  2. Karnofsky performance status (KPS) score of 80-100.
  3. Life expectancy of six months or greater.
  4. NSCLC of any histology.
  5. Resolution of all acute toxic effects of prior radiotherapy or surgical procedures to Grade ≤ 1 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
  6. 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.
  7. Able to abstain from taking prohibited drugs, either prescription or non-prescription, during the treatment phase of the study.
  8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  9. Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.

Exclusion Criteria:

  1. Active autoimmune disease or condition requiring chronic immunosuppressive therapy
  2. Any clinically significant condition that prohibits the initiation of standard of care.

  3. Malignancies within the prior three years, except for:

    • treated in situ carcinomas or non-melanoma skin cancer.
    • adequately treated early stage breast cancer.
    • superficial bladder cancer.
    • non-metastatic prostate cancer with a normal prostate-specific antigen (PSA) level.
  4. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of brain or leptomeningeal disease.

  5. Clinically significant disorders or conditions including

    • cardiovascular system.
    • renal system.
    • hepatic organ system.
    • coagulation disorders.
  6. Clinically significant infections, including human immunodeficiency virus (HIV), syphilis, and active hepatitis B or C.
  7. Pregnant or breastfeeding.
  8. Any serious medical condition or illness considered by the investigator to constitute an unwarranted high risk for investigational treatment.

Sites / Locations

  • Cancer Research Network of Nebraska / Oncology Associates

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Sequential, no radiation

Concurrent, no radiation

Sequential, radiation

Concurrent, radiation

Arm Description

AGS-003-LNG initiated after completion of platinum doublet chemotherapy. AGS-003-LNG induction = 1 dose administered every 3 weeks for 5 doses. Booster doses will then be administered every 12 weeks. A dose of AGS-003-LNG consists of (1.2 x 10-7 Dendritic cells.) Platinum-doublet chemotherapy can be any of the following determined by PI Carboplatin/Abraxane: ABRAXANE is 100 mg/m2 i.v. over 30 minutes on Days 1, 8, & 15 of each 21-day cycle; carboplatin Area Under Curve (AUC) 6 (C&G) on Day 1 of each 21-day cycle immediately after ABRAXANE. Carboplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with carboplatin AUC 6 (C&G) i.v. 30 minutes after ALIMTA. Cisplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day with cisplatin 75 mg/m2 i.v., 30 minutes after ALIMTA. Carboplatin/Taxol TAXOL administered i.v. over 24 hrs at a dose of 135 mg/m2 followed by carboplatin, AUC 6 (C&G).

AGS-003-LNG dosing initiated concurrently or subsequent to 3rd cycle of platinum doublet chemotherapy & radiation therapy. AGS-003-LNG induction = 1 dose administered every 3 wks for 5 doses. Booster doses will then be administered every 12 wks. A dose of AGS-003-LNG =1.2 x 10-7 Dendritic cells. Platinum-doublet chemotherapy can be any of the following determined by PI Carboplatin/Abraxane: ABRAXANE is 100 mg/m2 i.v. over 30 minutes on Days 1, 8, & 15 of each 21-day cycle; carboplatin AUC 6 (C&G) on Day 1 of each 21-day cycle immediately after ABRAXANE. Carboplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with carboplatin AUC 6 (C&G) i.v. 30 minutes after ALIMTA. Cisplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day with cisplatin 75 mg/m2 i.v., 30 minutes after ALIMTA. Carboplatin/Taxol TAXOL administered i.v. over 24 hrs at a dose of 135 mg/m2 followed by carboplatin, AUC 6 (C&G).

AGS-003-LNG initiated after completion of platinum doublet chemotherapy. AGS-003-LNG induction = 1 dose administered every 3 weeks for 5 doses. Booster doses will then be administered every 12 weeks. A dose of AGS-003-LNG consists of (1.2 x 10-7 Dendritic cells.) Platinum-doublet chemotherapy can be any of the following determined by PI Carboplatin/Abraxane: ABRAXANE is 100 mg/m2 i.v. over 30 minutes on Days 1, 8, & 15 of each 21-day cycle; carboplatin AUC 6 (C&G) on Day 1 of each 21-day cycle immediately after ABRAXANE. Carboplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with carboplatin AUC 6 (C&G) i.v. 30 minutes after ALIMTA. Cisplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day with cisplatin 75 mg/m2 i.v., 30 minutes after ALIMTA. Carboplatin/Taxol TAXOL administered i.v. over 24 hrs at a dose of 135 mg/m2 followed by carboplatin, AUC 6 (C&G). Radiation therapy per PI

AGS-003-LNG dosing initiated concurrently during or subsequent to the 3rd cycle (3-week cycle) of platinum doublet chemotherapy & radiation therapy. AGS-003-LNG induction = 1 dose administered every 3 wks for 5 doses. Booster doses administered every 12 wks. A dose of AGS-003-LNG =1.2 x 10-7 Dendritic cells. Platinum-doublet chemotherapy choice of the following determined by PI Carboplatin/Abraxane: ABRAXANE is 100 mg/m2 i.v. over 30 minutes on Days 1, 8, & 15 of each 21-day cycle; carboplatin AUC 6 (C&G) on Day 1 of each 21-day cycle immediately after ABRAXANE. Carboplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with carboplatin AUC 6 (C&G) i.v. 30 minutes after ALIMTA. Cisplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day with cisplatin 75 mg/m2 i.v., 30 minutes after ALIMTA. Carboplatin/Taxol TAXOL administered i.v. over 24 hrs at a dose of 135 mg/m2 followed by carboplatin, AUC 6 (C&G). Radiation therapy per PI.

Outcomes

Primary Outcome Measures

Safety - Adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V4.03
Safety of AGS-003-LNG for subjects who receive 1 or more doses of AGS-003-LNG in combination with standard platinum-doublet chemotherapy with or without radiation. Adverse events will be collected per CTCAE V4.03.
Immunogenicity - Generation of Cluster of Differentiation-8 (CD8)+ Cluster of Differentiation (CD28)+ memory T-cells
Generation of CD8+CD28+ memory T-cells against tumor associated antigens in subject receiving 5 or more doses of AGS-003-LNG.

Secondary Outcome Measures

Efficacy - Overall survival
While the study is not powered for efficacy Overall Survival (including median and one year survival) be analyzed as an exploratory endpoints.
Efficacy - Progression-free survival as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
While the study is not powered for efficacy, Progression Free Survival will be analyzed as an exploratory endpoint.
Efficacy - Objective response rate. The number of patients with a Complete Response or Partial Response.
While the study is not powered for efficacy Objective Response Rate will be analyzed as an exploratory endpoint.
Feasibility - Number of patients with a success in the manufacture of AGS-003-LNG.
AGS-003-LNG manufacturing success rate for non small cell lung cancer tumor RNA isolation from surgical resection.

Full Information

First Posted
January 12, 2016
Last Updated
March 3, 2022
Sponsor
GU Research Network, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02662634
Brief Title
A Safety and Feasibility Study of AGS-003-LNG for the Treatment of Stage 3 Non Small Cell Lung Cancer
Official Title
A Safety and Feasibility Study of AGS-003-LNG for the Treatment of Stage 3 Non Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Withdrawn
Study Start Date
March 2016 (undefined)
Primary Completion Date
March 2018 (Anticipated)
Study Completion Date
March 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GU Research Network, LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Feasibility and Safety study of autologous dendritic cell immunotherapy (AGS-003-LNG) in patients with resectable non-small cell lung cancer.
Detailed Description
Feasibility and Safety study of autologous dendritic cell immunotherapy (AGS-003-LNG) in patients with resectable non-small cell lung cancer. Non-small cell lung cancer tumor will be resected from the patient. RNA from the tumor will be amplified and subsequently electroporated into matured, autologous dendritic cells. The dendritic cells with tumor RNA will be dosed back to the patient. Study will investigate feasibility and safety.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer (NSCLC)
Keywords
NSCLC, resectable, non-small cell lung cancer, immunotherapy, autologous, dendritic cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sequential, no radiation
Arm Type
Experimental
Arm Description
AGS-003-LNG initiated after completion of platinum doublet chemotherapy. AGS-003-LNG induction = 1 dose administered every 3 weeks for 5 doses. Booster doses will then be administered every 12 weeks. A dose of AGS-003-LNG consists of (1.2 x 10-7 Dendritic cells.) Platinum-doublet chemotherapy can be any of the following determined by PI Carboplatin/Abraxane: ABRAXANE is 100 mg/m2 i.v. over 30 minutes on Days 1, 8, & 15 of each 21-day cycle; carboplatin Area Under Curve (AUC) 6 (C&G) on Day 1 of each 21-day cycle immediately after ABRAXANE. Carboplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with carboplatin AUC 6 (C&G) i.v. 30 minutes after ALIMTA. Cisplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day with cisplatin 75 mg/m2 i.v., 30 minutes after ALIMTA. Carboplatin/Taxol TAXOL administered i.v. over 24 hrs at a dose of 135 mg/m2 followed by carboplatin, AUC 6 (C&G).
Arm Title
Concurrent, no radiation
Arm Type
Experimental
Arm Description
AGS-003-LNG dosing initiated concurrently or subsequent to 3rd cycle of platinum doublet chemotherapy & radiation therapy. AGS-003-LNG induction = 1 dose administered every 3 wks for 5 doses. Booster doses will then be administered every 12 wks. A dose of AGS-003-LNG =1.2 x 10-7 Dendritic cells. Platinum-doublet chemotherapy can be any of the following determined by PI Carboplatin/Abraxane: ABRAXANE is 100 mg/m2 i.v. over 30 minutes on Days 1, 8, & 15 of each 21-day cycle; carboplatin AUC 6 (C&G) on Day 1 of each 21-day cycle immediately after ABRAXANE. Carboplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with carboplatin AUC 6 (C&G) i.v. 30 minutes after ALIMTA. Cisplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day with cisplatin 75 mg/m2 i.v., 30 minutes after ALIMTA. Carboplatin/Taxol TAXOL administered i.v. over 24 hrs at a dose of 135 mg/m2 followed by carboplatin, AUC 6 (C&G).
Arm Title
Sequential, radiation
Arm Type
Experimental
Arm Description
AGS-003-LNG initiated after completion of platinum doublet chemotherapy. AGS-003-LNG induction = 1 dose administered every 3 weeks for 5 doses. Booster doses will then be administered every 12 weeks. A dose of AGS-003-LNG consists of (1.2 x 10-7 Dendritic cells.) Platinum-doublet chemotherapy can be any of the following determined by PI Carboplatin/Abraxane: ABRAXANE is 100 mg/m2 i.v. over 30 minutes on Days 1, 8, & 15 of each 21-day cycle; carboplatin AUC 6 (C&G) on Day 1 of each 21-day cycle immediately after ABRAXANE. Carboplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with carboplatin AUC 6 (C&G) i.v. 30 minutes after ALIMTA. Cisplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day with cisplatin 75 mg/m2 i.v., 30 minutes after ALIMTA. Carboplatin/Taxol TAXOL administered i.v. over 24 hrs at a dose of 135 mg/m2 followed by carboplatin, AUC 6 (C&G). Radiation therapy per PI
Arm Title
Concurrent, radiation
Arm Type
Experimental
Arm Description
AGS-003-LNG dosing initiated concurrently during or subsequent to the 3rd cycle (3-week cycle) of platinum doublet chemotherapy & radiation therapy. AGS-003-LNG induction = 1 dose administered every 3 wks for 5 doses. Booster doses administered every 12 wks. A dose of AGS-003-LNG =1.2 x 10-7 Dendritic cells. Platinum-doublet chemotherapy choice of the following determined by PI Carboplatin/Abraxane: ABRAXANE is 100 mg/m2 i.v. over 30 minutes on Days 1, 8, & 15 of each 21-day cycle; carboplatin AUC 6 (C&G) on Day 1 of each 21-day cycle immediately after ABRAXANE. Carboplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with carboplatin AUC 6 (C&G) i.v. 30 minutes after ALIMTA. Cisplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day with cisplatin 75 mg/m2 i.v., 30 minutes after ALIMTA. Carboplatin/Taxol TAXOL administered i.v. over 24 hrs at a dose of 135 mg/m2 followed by carboplatin, AUC 6 (C&G). Radiation therapy per PI.
Intervention Type
Biological
Intervention Name(s)
AGS-003-LNG
Intervention Description
autologous dendritic cell immunotherapy
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Paraplatin
Intervention Description
Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."
Intervention Type
Drug
Intervention Name(s)
Abraxane
Other Intervention Name(s)
Protein-bound paclitaxel, nano-particle albumin-bound paclitaxel, nab-paclitaxel
Intervention Description
Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.
Intervention Type
Drug
Intervention Name(s)
Alimta
Other Intervention Name(s)
Pemetrexed
Intervention Description
By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cell
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Cisplatinum, platamin, neoplatin, cismaplat, cis-diamminedichloroplatinum(II)
Intervention Description
Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis
Intervention Type
Drug
Intervention Name(s)
Taxol
Other Intervention Name(s)
Paclitaxel
Intervention Description
Mechanism of action involves interference with the normal breakdown of microtubules during cell division.
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Intervention Description
Causes DNA strand breaks.
Primary Outcome Measure Information:
Title
Safety - Adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V4.03
Description
Safety of AGS-003-LNG for subjects who receive 1 or more doses of AGS-003-LNG in combination with standard platinum-doublet chemotherapy with or without radiation. Adverse events will be collected per CTCAE V4.03.
Time Frame
2 Years
Title
Immunogenicity - Generation of Cluster of Differentiation-8 (CD8)+ Cluster of Differentiation (CD28)+ memory T-cells
Description
Generation of CD8+CD28+ memory T-cells against tumor associated antigens in subject receiving 5 or more doses of AGS-003-LNG.
Time Frame
After 5th dose of AGS-003-LNG. Within 6 months.
Secondary Outcome Measure Information:
Title
Efficacy - Overall survival
Description
While the study is not powered for efficacy Overall Survival (including median and one year survival) be analyzed as an exploratory endpoints.
Time Frame
2 Years
Title
Efficacy - Progression-free survival as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Description
While the study is not powered for efficacy, Progression Free Survival will be analyzed as an exploratory endpoint.
Time Frame
2 Years
Title
Efficacy - Objective response rate. The number of patients with a Complete Response or Partial Response.
Description
While the study is not powered for efficacy Objective Response Rate will be analyzed as an exploratory endpoint.
Time Frame
2 Years
Title
Feasibility - Number of patients with a success in the manufacture of AGS-003-LNG.
Description
AGS-003-LNG manufacturing success rate for non small cell lung cancer tumor RNA isolation from surgical resection.
Time Frame
1 Month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 19 years. Newly diagnosed non-small cell lung cancer indicated for routine lobectomy, mediastinoscopy, wedge resection, thoracotomy or Video-assisted thoracoscopic surgery (VATS) procedures with tumor collection. Stage III (T1-3, N1-2, M0) of any histology. Scheduled for routine lobectomy, mediastinoscopy, wedge resection, thoracotomy or VATS procedures. Signed and dated informed consent document for study participation. After tumor collection, potential subjects must meet all the following criteria to be enrolled in study treatment: Successful RNA isolation and amplification from tumor sample (as determined by Argos). Karnofsky performance status (KPS) score of 80-100. Life expectancy of six months or greater. NSCLC of any histology. Resolution of all acute toxic effects of prior radiotherapy or surgical procedures to Grade ≤ 1 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. 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. Able to abstain from taking prohibited drugs, either prescription or non-prescription, during the treatment phase of the study. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment. Exclusion Criteria: Active autoimmune disease or condition requiring chronic immunosuppressive therapy Any clinically significant condition that prohibits the initiation of standard of care. Malignancies within the prior three years, except for: treated in situ carcinomas or non-melanoma skin cancer. adequately treated early stage breast cancer. superficial bladder cancer. non-metastatic prostate cancer with a normal prostate-specific antigen (PSA) level. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of brain or leptomeningeal disease. Clinically significant disorders or conditions including cardiovascular system. renal system. hepatic organ system. coagulation disorders. Clinically significant infections, including human immunodeficiency virus (HIV), syphilis, and active hepatitis B or C. Pregnant or breastfeeding. Any serious medical condition or illness considered by the investigator to constitute an unwarranted high risk for investigational treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luke T Nordquist, MD
Organizational Affiliation
Cancer Research Network of Nebraska
Official's Role
Study Director
Facility Information:
Facility Name
Cancer Research Network of Nebraska / Oncology Associates
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68118
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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A Safety and Feasibility Study of AGS-003-LNG for the Treatment of Stage 3 Non Small Cell Lung Cancer

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