Trial Outcomes & Findings for MnSOD (Esophageal Protectant) to Prevent Esophagitis During Radiation/Chemotherapy Treatment for Non-Small Cell Lung Cancer (NSCLC) (NCT NCT00618917)

Last Updated: 2021-11-12

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

18 participants

Primary outcome timeframe

Every 8 weeks, up to 2 years

Results posted on

2021-11-12

Participant Flow

Participant milestones

Participant milestones
Measure	MnSOD PL (0.3 mg) + Paclitaxel + Carboplatin 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 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 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.
Overall Study STARTED	4	3	11
Overall Study COMPLETED	3	3	11
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Radiation + MnSOD PL (0.3 mg) + Paclitaxel + Carboplatin n=4 Participants 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 (3.0 mg) + Paclitaxel + Carboplatin n=3 Participants 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 (30.0 mg) + Paclitaxel + Carboplatin n=11 Participants 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.	Total n=18 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	70 years n=7 Participants	64 years n=5 Participants	65 years n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Every 8 weeks, up to 2 years

Population: Patients that received at least one dose of MnSOD.

Outcome measures

Outcome measures
Measure	Radiation + MnSOD PL + Paclitaxel + Carboplatin n=18 Participants 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.
Determination of Recommended Phase II Dose of MnSOD/Plasmid DNA	30 milligrams

PRIMARY outcome

Timeframe: Up to 2 years

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

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

Outcome measures

Outcome measures
Measure	Radiation + MnSOD PL + Paclitaxel + Carboplatin n=8 Participants 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-induced Esophageal Toxicity	0 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: Patients that received 30.0 mg MnSOD and evaluable for response.

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.

Outcome measures

Outcome measures
Measure	Radiation + MnSOD PL + Paclitaxel + Carboplatin n=8 Participants 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.
Overall (Objective) Response Partial Response per RECIST	3 Participants
Overall (Objective) Response Stable Disease per RECIST	2 Participants
Overall (Objective) Response Progressive Disease per RECIST	2 Participants

SECONDARY outcome

Timeframe: Up to 5 years

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

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

Outcome measures

Outcome measures
Measure	Radiation + MnSOD PL + Paclitaxel + Carboplatin n=8 Participants 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.
Overall Survival (OS)	31 months CI not reached due to low patient accrual.

SECONDARY outcome

Timeframe: Up to 5 years

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

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.

Outcome measures

Outcome measures
Measure	Radiation + MnSOD PL + Paclitaxel + Carboplatin n=7 Participants 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.
Time to Disease Progression	26 months Interval 15.3 to Upper bound of CI not reached due to low patient accrual.

Adverse Events

MnSOD PL (0.3 mg) + Paclitaxel + Carboplatin

Serious events: 1 serious events

Other events: 4 other events

Deaths: 1 deaths

MnSOD PL (3.0 mg) + Paclitaxel + Carboplatin

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

MnSOD PL (30.0 mg) + Paclitaxel + Carboplatin

Serious events: 7 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Barbara Stadterman, MPH, MCCR, Regulatory Supervisor, CRS

UPMC Hillman Cancer Center

Phone: 412-647-5554

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place