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

NCT ID: NCT00618917

Last Updated: 2021-11-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-11
• Study Completion Date: 2011-08-11

Brief Summary

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).

Detailed Description

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.

Conditions

Esophageal; Toxicity

Keywords

NSCLC; lung cancer; chemotherapy; radiation therapy; radiation toxicity

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiation + MnSOD PL + Paclitaxel + Carboplatin

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.

Group Type: EXPERIMENTAL

Manganese Superoxide Dismutase Plasmid Liposome

Intervention Type: GENETIC

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

Intervention Type: DRUG

Chemotherapy to stop the growth of tumor cells.

paclitaxel

Intervention Type: DRUG

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 Therapy

Intervention Type: 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.

Interventions

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.

Intervention Type: GENETIC

carboplatin

Chemotherapy to stop the growth of tumor cells.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Radiation Therapy

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.

Intervention Type: RADIATION

Other Intervention Names

MnSOD/PL; Paraplatin; Taxol

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically documented NSCLC including squamous cell carcinoma, adenocarcinoma (including bronchoalveolar cell), and large cell anaplastic carcinoma (including giant and clear cell carcinomas) and poorly differentiated non-small cell lung cancer. Totally resected tumors are excluded.
• Subjects must be without evidence of M0.
• Subjects with T1 or T2 disease with N2 or tumor stage 3, lymph node metastasis 1-2 ( stage 1) disease (Stage IIIA) are eligible if they are medically inoperable. Subjects with T4 with any N or any T with N3 disease are eligible. Radiographic evidence of mediastinal lymph nodes >2.0 cm in the largest diameter is sufficient to stage N2 or N3 disease. If the largest mediastinal node is < 2.0 cm in diameter and this is the basis for stage III disease, then at least one of the nodes must be proven positive cytologically or histologically.
• Subjects with tumors adjacent to a vertebral body are eligible as long as all gross disease can be encompassed in the radiation boost field. The boost volume must be limited to < 50% of the ipsilateral lung volume.
• Subjects with a pleural effusion that is a transudate, cytologically negative and non-bloody are eligible if the radiation oncologists feel the tumor can still be encompassed within a reasonable field of radiotherapy. Exudative, bloody, or cytologically malignant effusions are ineligible. If a pleural effusion can be seen on the chest CT but not on chest X-ray and is too small to tap, the subject will be eligible.
• Subjects must be deemed a suitable candidate for protocol treatment by both Radiation Oncology and Medical Oncology
• Subjects must have a Performance Status > 70 (Karnofsky Performance Scale).
• Subjects Weight loss < 10% in 3 months prior to diagnosis.
• Subjects must be male or female > 18 years.
• Subjects must have had no prior systemic chemotherapy, radiation therapy to the thorax, or total surgical resection.
• At least 3 weeks since formal exploratory thoracotomy and the subject has recovered from surgery, or 1 week from diagnostic thoracoscopy.
• Laboratory values must be as follows: (See Section 6.1 of the full protocol for required timing): Granulocytes > 2,000/ml, Platelets > 100,000/ml, Hemoglobin* > 8 mg/dl, Bilirubin < 1.5 x normal, Creatinine clearance > 50 ml/n (24 hour or calculated, forced expiratory volume at one second > 800 cc. Note: *Physician can maintain a subject's hemoglobin with the use of Erythropoetin or transfusions prophylactic use of G-CSF (colony stimulating factor, is not permitted).
• Subjects must have a MRI or CT brain scan within 4 weeks prior to study entry to rule out asymptomatic brain metastases.
• Subjects must be informed of the investigational nature of the study and sign an informed consent form and have no serious medical or psychiatric illnesses that would prevent informed consent.
• No history of serious cardiac disease that is not adequately controlled.
• Female subjects must be non-pregnant and non-lactating. Female subjects of childbearing potential must implement an effective method of contraception during the study. All women of childbearing potential must have a pre-study negative serum or urine pregnancy test within 7 days prior to study entry.

Exclusion Criteria

• Inability to meet any of the above eligibility requirements

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Joel Greenberger

OTHER

Sponsor Role: lead

Responsible Party

Joel Greenberger

Professor, Chairman of Radiation Oncology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Joel Greenberger, MD

Role: PRINCIPAL_INVESTIGATOR

UPMC Hillman Cancer Center

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

UPCI 01-054

Identifier Type: OTHER

Identifier Source: secondary_id

01-054

Identifier Type: -

Identifier Source: org_study_id