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

NCT00618917 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 01-054UPCI 01-054
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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).

Conditions

Esophageal; Toxicity

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Determination of Recommended Phase II Dose of MnSOD/Plasmid DNA

  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).

  Every 8 weeks, up to 2 years

• Radiation-induced Esophageal Toxicity

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

  Up to 2 years

Secondary Outcomes (3)

• Overall (Objective) Response

  Up to 2 years

• Overall Survival (OS)

  Up to 5 years

• Time to Disease Progression

  Up to 5 years

Study Arms (1)

Radiation + MnSOD PL + Paclitaxel + Carboplatin

EXPERIMENTAL

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.

Genetic: Manganese Superoxide Dismutase Plasmid Liposome; Drug: carboplatin; Drug: paclitaxel; Radiation: Radiation Therapy

Interventions

Manganese Superoxide Dismutase Plasmid Liposome 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.

Also known as: MnSOD/PL

Radiation + MnSOD PL + Paclitaxel + Carboplatin

carboplatin DRUG

Chemotherapy to stop the growth of tumor cells.

Also known as: Paraplatin

Radiation + MnSOD PL + Paclitaxel + Carboplatin

paclitaxel 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.

Also known as: Taxol

Radiation + MnSOD PL + Paclitaxel + Carboplatin

Radiation Therapy 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.

Radiation + MnSOD PL + Paclitaxel + Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Inability to meet any of the above eligibility requirements

Sponsors & Collaborators

• Joel Greenberger: lead

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Radiation Injuries

Interventions

Carboplatin; Paclitaxel; Radiotherapy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Therapeutics

Results Point of Contact

• Title: Barbara Stadterman, MPH, MCCR, Regulatory Supervisor, CRS
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

412-647-5554

Study Officials

• Joel Greenberger, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Chairman of Radiation Oncology

Study Record Dates

• First Submitted: February 6, 2008
• First Posted: February 20, 2008
• Study Start: November 11, 2005
• Primary Completion: February 26, 2010
• Study Completion: August 11, 2011
• Last Updated: November 12, 2021
• Results First Posted: November 12, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)