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

NCT ID: NCT02662634

Last Updated: 2022-03-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2018-03-31

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.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

AGS-003-LNG

Intervention Type: BIOLOGICAL

autologous dendritic cell immunotherapy

Carboplatin

Intervention Type: DRUG

Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."

Abraxane

Intervention Type: DRUG

Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.

Alimta

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis

Taxol

Intervention Type: DRUG

Mechanism of action involves interference with the normal breakdown of microtubules during cell division.

Radiation Therapy

Intervention Type: RADIATION

Causes DNA strand breaks.

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).

Group Type: EXPERIMENTAL

AGS-003-LNG

Intervention Type: BIOLOGICAL

autologous dendritic cell immunotherapy

Carboplatin

Intervention Type: DRUG

Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."

Abraxane

Intervention Type: DRUG

Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.

Alimta

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis

Taxol

Intervention Type: DRUG

Mechanism of action involves interference with the normal breakdown of microtubules during cell division.

Radiation Therapy

Intervention Type: RADIATION

Causes DNA strand breaks.

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

Group Type: EXPERIMENTAL

AGS-003-LNG

Intervention Type: BIOLOGICAL

autologous dendritic cell immunotherapy

Carboplatin

Intervention Type: DRUG

Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."

Abraxane

Intervention Type: DRUG

Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.

Alimta

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis

Taxol

Intervention Type: DRUG

Mechanism of action involves interference with the normal breakdown of microtubules during cell division.

Radiation Therapy

Intervention Type: RADIATION

Causes DNA strand breaks.

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.

Group Type: EXPERIMENTAL

AGS-003-LNG

Intervention Type: BIOLOGICAL

autologous dendritic cell immunotherapy

Carboplatin

Intervention Type: DRUG

Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."

Abraxane

Intervention Type: DRUG

Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.

Alimta

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis

Taxol

Intervention Type: DRUG

Mechanism of action involves interference with the normal breakdown of microtubules during cell division.

Radiation Therapy

Intervention Type: RADIATION

Causes DNA strand breaks.

Interventions

AGS-003-LNG

autologous dendritic cell immunotherapy

Intervention Type: BIOLOGICAL

Carboplatin

Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."

Intervention Type: DRUG

Abraxane

Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.

Intervention Type: 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

Intervention Type: DRUG

Cisplatin

Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis

Intervention Type: DRUG

Taxol

Mechanism of action involves interference with the normal breakdown of microtubules during cell division.

Intervention Type: DRUG

Radiation Therapy

Causes DNA strand breaks.

Intervention Type: RADIATION

Other Intervention Names

Paraplatin; Protein-bound paclitaxel; nano-particle albumin-bound paclitaxel; nab-paclitaxel; Pemetrexed; Cisplatinum; platamin; neoplatin; cismaplat; cis-diamminedichloroplatinum(II); Paclitaxel

Eligibility 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.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GU Research Network, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luke T Nordquist, MD

Role: STUDY_DIRECTOR

Cancer Research Network of Nebraska

Locations

Cancer Research Network of Nebraska / Oncology Associates

Omaha, Nebraska, United States

Countries

United States

Other Identifiers

AGS-003-024

Identifier Type: -

Identifier Source: org_study_id