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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Esophageal, Toxicity

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Trial Information

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

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.

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

feasibility and safety

Outcome Time Frame:

The endpoint will be the proportion of toxicities attributed to administration of MnSOD plasmid liposome.

Safety Issue:


Principal Investigator

Ahmad Tarhini, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh Cancer Institute/Univeristy of Pittsburgh Medical Center, Cancer Centers


United States: Food and Drug Administration

Study ID:




Start Date:

November 2005

Completion Date:

September 2015

Related Keywords:

  • Esophageal
  • Toxicity
  • lung cancer
  • chemotherapy
  • radiation therapy
  • radiation toxicity
  • Carcinoma, Non-Small-Cell Lung
  • Esophageal Diseases
  • Lung Neoplasms



University of Pittsburgh Pittsburgh, Pennsylvania  15261