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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02662634
Recruitment Status : Recruiting
First Posted : January 25, 2016
Last Update Posted : March 25, 2016
Sponsor:
Collaborator:
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer (NSCLC) Biological: AGS-003-LNG Drug: Carboplatin Drug: Abraxane Drug: Alimta Drug: Cisplatin Drug: Taxol Radiation: Radiation Therapy Phase 2

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Safety and Feasibility Study of AGS-003-LNG for the Treatment of Stage 3 Non Small Cell Lung Cancer
Study Start Date : March 2016
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : March 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Sequential, no radiation

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).

Biological: AGS-003-LNG
autologous dendritic cell immunotherapy
Drug: Carboplatin
Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."
Other Name: Paraplatin
Drug: Abraxane
Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.
Other Names:
  • Protein-bound paclitaxel
  • nano-particle albumin-bound paclitaxel
  • nab-paclitaxel
Drug: Alimta
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
Other Name: Pemetrexed
Drug: Cisplatin
Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis
Other Names:
  • Cisplatinum
  • platamin
  • neoplatin
  • cismaplat
  • cis-diamminedichloroplatinum(II)
Drug: Taxol
Mechanism of action involves interference with the normal breakdown of microtubules during cell division.
Other Name: Paclitaxel
Radiation: Radiation Therapy
Causes DNA strand breaks.
Experimental: Concurrent, no radiation

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).

Biological: AGS-003-LNG
autologous dendritic cell immunotherapy
Drug: Carboplatin
Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."
Other Name: Paraplatin
Drug: Abraxane
Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.
Other Names:
  • Protein-bound paclitaxel
  • nano-particle albumin-bound paclitaxel
  • nab-paclitaxel
Drug: Alimta
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
Other Name: Pemetrexed
Drug: Cisplatin
Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis
Other Names:
  • Cisplatinum
  • platamin
  • neoplatin
  • cismaplat
  • cis-diamminedichloroplatinum(II)
Drug: Taxol
Mechanism of action involves interference with the normal breakdown of microtubules during cell division.
Other Name: Paclitaxel
Radiation: Radiation Therapy
Causes DNA strand breaks.
Experimental: Sequential, radiation

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

Biological: AGS-003-LNG
autologous dendritic cell immunotherapy
Drug: Carboplatin
Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."
Other Name: Paraplatin
Drug: Abraxane
Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.
Other Names:
  • Protein-bound paclitaxel
  • nano-particle albumin-bound paclitaxel
  • nab-paclitaxel
Drug: Alimta
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
Other Name: Pemetrexed
Drug: Cisplatin
Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis
Other Names:
  • Cisplatinum
  • platamin
  • neoplatin
  • cismaplat
  • cis-diamminedichloroplatinum(II)
Drug: Taxol
Mechanism of action involves interference with the normal breakdown of microtubules during cell division.
Other Name: Paclitaxel
Radiation: Radiation Therapy
Causes DNA strand breaks.
Experimental: Concurrent, radiation

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.

Biological: AGS-003-LNG
autologous dendritic cell immunotherapy
Drug: Carboplatin
Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."
Other Name: Paraplatin
Drug: Abraxane
Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.
Other Names:
  • Protein-bound paclitaxel
  • nano-particle albumin-bound paclitaxel
  • nab-paclitaxel
Drug: Alimta
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
Other Name: Pemetrexed
Drug: Cisplatin
Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis
Other Names:
  • Cisplatinum
  • platamin
  • neoplatin
  • cismaplat
  • cis-diamminedichloroplatinum(II)
Drug: Taxol
Mechanism of action involves interference with the normal breakdown of microtubules during cell division.
Other Name: Paclitaxel
Radiation: Radiation Therapy
Causes DNA strand breaks.


Outcome Measures

Primary Outcome Measures :
  1. Safety - Adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V4.03 [ Time Frame: 2 Years ]
    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.

  2. Immunogenicity - Generation of Cluster of Differentiation-8 (CD8)+ Cluster of Differentiation (CD28)+ memory T-cells [ Time Frame: After 5th dose of AGS-003-LNG. Within 6 months. ]
    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 :
  1. Efficacy - Overall survival [ Time Frame: 2 Years ]
    While the study is not powered for efficacy Overall Survival (including median and one year survival) be analyzed as an exploratory endpoints.

  2. Efficacy - Progression-free survival as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. [ Time Frame: 2 Years ]
    While the study is not powered for efficacy, Progression Free Survival will be analyzed as an exploratory endpoint.

  3. Efficacy - Objective response rate. The number of patients with a Complete Response or Partial Response. [ Time Frame: 2 Years ]
    While the study is not powered for efficacy Objective Response Rate will be analyzed as an exploratory endpoint.

  4. Feasibility - Number of patients with a success in the manufacture of AGS-003-LNG. [ Time Frame: 1 Month ]
    AGS-003-LNG manufacturing success rate for non small cell lung cancer tumor RNA isolation from surgical resection.


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02662634


Contacts
Contact: Tony Romero, MS, CCRC 402-697-2229 tromero@gucancer.com

Locations
United States, Nebraska
Cancer Research Network of Nebraska / Oncology Associates Recruiting
Omaha, Nebraska, United States, 68118
Contact: Tony Romero, MS, CCRC    402-697-2229    tromero@gucancer.com   
Principal Investigator: Stephen Lemon, MD         
Sponsors and Collaborators
GU Research Network, LLC
Cancer Research Network of Nebraska/Oncology Associates
Investigators
Study Director: Luke T Nordquist, MD Cancer Research Network of Nebraska
More Information

Responsible Party: GU Research Network, LLC
ClinicalTrials.gov Identifier: NCT02662634     History of Changes
Other Study ID Numbers: AGS-003-024
First Posted: January 25, 2016    Key Record Dates
Last Update Posted: March 25, 2016
Last Verified: March 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by GU Research Network, LLC:
NSCLC
resectable
non-small cell lung cancer
immunotherapy
autologous
dendritic cell

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin
Carboplatin
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors