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Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Manganese

Superoxide Dismutase

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MnSOD PL (0.3, 3, or 30 mg) + (Paclitaxel + Carboplatin (45mg/m\^2)) + Radiation 1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks.

15 ml of liquid that contains either 0.3 mg, 3.0 mg or 30.0 mg (depending on which cohort is open when the subject is entered) of MnSOD PL This will be given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.

Manganese Superoxide Dismutase Plasmid Liposome

Chemotherapy to stop the growth of tumor cells.

carboplatin

Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.

paclitaxel

1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks.

Radiation Therapy

Joel Greenberger, MD

This is a Phase I-II study evaluating the feasibility, safety, and efficacy of swallowed MnSOD plasmid/liposome (PL) transgene given as protection against radiation-induced esophagitis during concurrent paclitaxel and carboplatin chemotherapy with thoracic radiation in subjects with locally advanced non-small cell lung cancer (NSCLC).

This is a Phase I-II study evaluating the feasibility, safety, and efficacy of swallowed MnSOD plasmid/liposome (PL) transgene given as protection against radiation-induced esophagitis during concurrent paclitaxel and carboplatin chemotherapy with thoracic radiation in subjects with locally advanced non-small cell lung cancer (NSCLC). Phase I of the study will assess the feasibility and safety of MnSOD PL by dose escalation in 3 cohorts of 3 chemoradiotherapy subjects each (Cohort1 = 0.3 mg/dose, Cohort2 = 3 mg/dose, Cohort3 = 30 mg/dose). The highest dose completed (as determined by toxicity monitoring for 8 weeks from initial treatment) will be the starting dose for Phase II. Phase II will examine the efficacy of MnSOD PL by assessing the incidence of Grade 3 or 4 esophagitis in 27 additional chemoradiotherapy subjects. Incidence of esophageal toxicity, as well as clinical response to the combination of chemoradiotherapy with MnSOD PL are the outcomes of interest.

MnSOD (Esophageal Protectant) to Prevent Esophagitis During Radiation/Chemotherapy Treatment for Non-Small Cell Lung Cancer (NSCLC)

Chemotherapy (Paclitaxel and Carboplatin)and Thoracic Radiotherapy With Swallowed Manganese Superoxide Dismutase (MnSOD) Plasmid Liposome Protection in Patients With Locally Advanced Stage III Non-Small Cell Lung Cancer: A Phase I-II Study

The maximally tolerated dose (milligrams) defined as the highest dose with fewer than one-third of patients experiencing a dose-limiting toxicity (DLT) per CTCAE v3.0 due to MnSOD.

(Three patients treated at each at three tiers of 0.3, 3, and 30mg of MnSOD/plasmid DNA. If no DLTs (grade III/IV toxicity due to MnSOD PL) observed, the dose of MnSOD PL escalated to the next tier. If one DLT observed, the cohort is expanded to six patients. If two of six patients experienced a DLT, dose escalation stops and the next lowest dose declared maximum tolerated dose (MTD). If none of three or one of six patients experience DLT at the 30-mg tier, that dose is defined as the starting dose for the efficacy phase and the MTD would be undefined).

Number of patients experiencing grade III/IV esophageal toxicity per CTCAE v3.0.

Clinical Response per Response Evaluation Criteria in Solid Tumors (RECIST). Per RECIST v1.0: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease: Neither sufficient shrinkage (compared to baseline) to qualify for partial or complete response (CR or PR) nor sufficient increase (taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest) to qualify for progressive disease (PD). Progressive Disease (PD): At least a 20%increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

The length of time from start of treatment that diagnosed patients remain alive.

The length of time from start of treatment until patients first disease recurrence/progression. Per RECIST v1.0: Progressive Disease (PD): At least a 20%increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Joel Greenberger

Professor, Chairman of Radiation Oncology

NCI Common Terminology Criteria for Adverse Events CTCAE v 3.0 - Adverse Events: Grade 1 and Grade 2 events per CTCAE v3.0 Serious Adverse Events: Grade 3 and Grade 4 events per CTCAE v3.0

MnSOD PL (0.3 mg) + (Paclitaxel + Carboplatin (45mg/m\^2))

Manganese Superoxide Dismutase Plasmid Liposome: 15 ml of liquid that containing 0.3 mg of MnSOD PL This will be given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.

carboplatin: Chemotherapy to stop the growth of tumor cells.

paclitaxel: Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.

MnSOD PL (0.3 mg) + Paclitaxel + Carboplatin

MnSOD PL (3.0 mg) + (Paclitaxel + Carboplatin (45mg/m\^2))

Manganese Superoxide Dismutase Plasmid Liposome: 15 ml of liquid that containing 3.0 mg of MnSOD PL This will be given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.

carboplatin: Chemotherapy to stop the growth of tumor cells.

paclitaxel: Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.

MnSOD PL (3.0 mg) + Paclitaxel + Carboplatin

MnSOD PL (30.0 mg) + (Paclitaxel + Carboplatin (45mg/m\^2))

Manganese Superoxide Dismutase Plasmid Liposome: 15 ml of liquid that containing 30.0 mg of MnSOD PL This will be given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.

carboplatin: Chemotherapy to stop the growth of tumor cells.

paclitaxel: Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.

MnSOD PL (30.0 mg) + Paclitaxel + Carboplatin

Radiation + MnSOD PL (0.3 mg) + (Paclitaxel + Carboplatin (45mg/m\^2))

1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks.

Manganese Superoxide Dismutase Plasmid Liposome: 15 ml of liquid that contains 0.3 mg of MnSOD PL, given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.

carboplatin: Chemotherapy to stop the growth of tumor cells.

paclitaxel: Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.

Radiation + MnSOD PL (0.3 mg) + Paclitaxel + Carboplatin

Radiation + MnSOD PL (3.0 mg) + (Paclitaxel + Carboplatin (45mg/m\^2))

1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks.

Manganese Superoxide Dismutase Plasmid Liposome: 15 ml of liquid that contains 3.0 mg of MnSOD PL, given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.

carboplatin: Chemotherapy to stop the growth of tumor cells.

paclitaxel: Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.

Radiation + MnSOD PL (3.0 mg) + Paclitaxel + Carboplatin

Radiation + MnSOD PL (30.0 mg) + (Paclitaxel + Carboplatin (45mg/m\^2))

1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks.

Manganese Superoxide Dismutase Plasmid Liposome: 15 ml of liquid that contains 30.0 mg of MnSOD PL, given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.

carboplatin: Chemotherapy to stop the growth of tumor cells.

paclitaxel: Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.

Radiation + MnSOD PL (30.0 mg) + Paclitaxel + Carboplatin

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Patients that received at least one dose of MnSOD.

Barbara Stadterman, MPH, MCCR, Regulatory Supervisor, CRS

Radiation: 1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks.

MnSOD PL (0.3, 3, or 30 mg) + (Paclitaxel + Carboplatin (45mg/m\^2))

Manganese Superoxide Dismutase Plasmid Liposome: 15 ml of liquid that contains either 0.3 mg, 3.0 mg or 30.0 mg (depending on which cohort is open when the subject is entered) of MnSOD PL This will be given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.

carboplatin: Chemotherapy to stop the growth of tumor cells.

paclitaxel: Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.

Radiation + MnSOD PL + Paclitaxel + Carboplatin

Determination of Recommended Phase II Dose of MnSOD/Plasmid DNA

Radiation + MnSOD PL (30 mg) + (Paclitaxel + Carboplatin (45mg/m\^2))

Radiation: 1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks.

Manganese Superoxide Dismutase Plasmid Liposome: 15 ml of liquid that contains 30.0 mg of MnSOD PL on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.

carboplatin: Chemotherapy to stop the growth of tumor cells.

paclitaxel: Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.

Patients treated at 30mg MnSOD (the phase II dose).

Radiation-induced Esophageal Toxicity

Partial Response per RECIST

Stable Disease per RECIST

Progressive Disease per RECIST

MnSOD PL + Paclitaxel + Carboplatin

Patients that received 30.0 mg MnSOD and evaluable for response.

Overall (Objective) Response

Patients that received 30.0 mg MnSOD (may or may not have been evaluable for response).

Overall Survival (OS)

Patients who received 30.0 mg of MnSOD and were evaluable for response.

Time to Disease Progression

MnSOD PL (0.3 mg) + (Paclitaxel + Carboplatin (45mg/m\^2))

Manganese Superoxide Dismutase Plasmid Liposome: 15 ml of liquid that containing 0.3 mg of MnSOD PL, given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.

Paclitaxel: Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.

Carboplatin: Chemotherapy to stop the growth of tumor cells.

MnSOD PL (3.0 mg) + (Paclitaxel + Carboplatin (45mg/m\^2))

Manganese Superoxide Dismutase Plasmid Liposome: 15 ml of liquid that containing 3.0 mg of MnSOD PL, given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.

Paclitaxel: Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.

Carboplatin: Chemotherapy to stop the growth of tumor cells.

MnSOD PL (30.0 mg) + (Paclitaxel + Carboplatin (45mg/m\^2))

Manganese Superoxide Dismutase Plasmid Liposome: 15 ml of liquid that containing 30.0 mg of MnSOD PL, given on Day 1 and 3 of each week of the experimental treatment for a total of 14 doses.

Paclitaxel: Chemotherapy to stop the growth of tumor cells. This drug kills tumor cells by inducing multipolar divisions. Cells entering mitosis in the presence of concentrations of paclitaxel equivalent to those in human breast tumors form abnormal spindles that contain additional spindle poles.

Carboplatin: Chemotherapy to stop the growth of tumor cells.

Spots Global Cancer Trial Database for manganese superoxide dismutase plasmid liposome