Phase I Study of IV DOTAP: Cholesterol-Fus1 in Non-Small-Cell Lung Cancer

NCT00059605 | Completed Phase 1

• 1 other identifier: ID00-123
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find out the highest safe dose of DOTAP:Chol-fus1 that can be given to participants in the treatment of non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). This study is an attempt to transfer a gene (fus1) into cancer cells, using the drug DOTAP:Cholesterol-fus1. Researchers will also study the side effects of this experimental gene transfer at different doses, and will conduct tests to see if there are any effects on tumor size at different doses. Experimental transfer of the fus1 gene into humans has never been tried before. Objectives:

• Assess the toxicity of DOTAP:Cholesterol-fus1 Liposome Complex (DOTAP:Chol-fus1) administered intravenously.
• To determine the maximal tolerated dose and recommended phase II dose of DOTAP:Chol-fus1 administered intravenously.
• Assess the expression of fus1 following intravenous delivery of DOTAP:Chol-fus1 in tumor and normal bronchial epithelial cell biopsies.
• Assess any anti-cancer activity for DOTAP:Chol-fus1.

Conditions

Lung Cancer

Keywords

Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Lung Cancer; NSCLC; SCLC; DOTAP:Chol-fus1; gene; gene transfer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of DOTAP:Chol-fus1

  Before each dose level (3 weeks); Days 2, 3, and 8 after first dose, blood tests, vital signs, and side effects; and after every two treatment cycles or 6 weeks, tumor measured using CT or MRI scan.

Secondary Outcomes (1)

• Toxicity of the Intravenous DOTAP:Chol-fus1 complex

  Observation for 2 weeks follwing each treatment cycle (3 weeks) for toxicity.

Study Arms (1)

DOTAP:Chol-fus1

EXPERIMENTAL

Infusion intravenous once every 3 weeks

Genetic: DOTAP:Chol-fus1

Interventions

DOTAP:Chol-fus1 GENETIC

Infusion of DOTAP:Chol-fus1 by vein once every 3 weeks.

Also known as: DOTAP:Chol-FUS1 Liposomes

DOTAP:Chol-fus1

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically documented non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC)
• For NSCLC subjects: Locally advanced, unresectable, incurable stage IIIB (pleural effusion) or stage IV NSCLC, or recurrent NSCLC that is not potentially curable by radiotherapy or surgery. Patients must have received at least one prior platinum-based chemotherapy regimen for NSCLC. For SCLC subjects: Extensive disease or recurrent disease after initial treatment for limited disease. Patients must have received prior platinum-based chemotherapy or chemoradiotherapy. All subjects: There is no limit to the number of prior chemotherapy regimens received.
• Preference will be given to patients with tumors amenable to biopsy. In the expansion cohort at MTD, all patients must have tumor amenable to biopsy and must consent to biopsy.
• Karnofsky Performance Status \>= 70%, or Zubrod Performance Status \<= 1.
• Negative serum pregnancy test (serum HCG) if female and of childbearing potential. Since beta-HCG may be falsely elevated as a result of malignancy, women of child-bearing potential who have an elevated serum beta-HCG level are eligible for enrollment if they have two Transvaginal Ultrasound (TVUS) scans one week apart and serial beta-HCG levels two weeks apart that are inconsistent with pregnancy and a Gynecology consult to ensure that the beta- HCG level was at a value high enough to see pregnancy with TVUS. Subjects must agree to practice effective birth control during the study period.
• Negative serology for Human Immunodeficiency Virus.
• Patients must be \>/= 4 weeks beyond major surgical procedures such as thoracotomy, laparotomy or joint replacement, and must be \>/= 1.5 weeks beyond minor surgical procedures such as biopsy of subcutaneous tumors, pleuroscopy, etc, and must not have evidence of wound dehiscence, active wound infection, or comparable major residual complications of the surgery. Absolute neutrophil count (ANC) \> 1500 \* 10\*\*9/mm\*\*3, platelet count \> 100,000 \* 10\*\*9/mm\*\*3. Prothrombin time (PT) and Partial thromboplastin time (PTT) \< 1.25 times the institutional upper limit of normal.
• Adequate renal function documented by serum creatinine of \<= 1.5 mg/dl or calculated creatinine clearance \> 50 ml/min.
• Adequate hepatic function as documented by serum bilirubin\< 1.5 mg/dl and SGOT and SGPT \</= 1.5 \* upper limit of normal.
• FEV1 and corrected DLCO of \>/= 40% of predicted.
• Patients with asymptomatic brain metastases that have been treated are eligible if the following criteria are met: No history of seizures in the preceding 6 months. Definitive treatment must have been completed ≥4weeks prior to registration. Subjects must be off steroids that were being administered because of brain metastases or related symptoms for ≥2 weeks. Post-treatment imaging within 2 weeks of registration must demonstrate stability or regression of the brain metastases.
• Stable cardiac condition with a left ventricular ejection fraction \> 50%.
• Patients must have voluntarily signed an informed consent in accordance with institutional policies.

You may not qualify if:

• Females who are pregnant or breast-feeding.
• Patients who received investigational therapy, monoclonal antibody such as bevacizumab or cetuximab, or who received radiotherapy to the skull, spine, thorax or pelvis within 30 days of entry into the protocol. Patients are permitted to have received palliative radiotherapy to an extremity provided at least 14 days has elapsed since completion of therapy, provided the patient received no more than 10 radiotherapy fractions and a dose no higher than 30 Gy to that site, and provided skull, spine, thorax or pelvis were not in the radiotherapy field.
• Active systemic viral, bacterial or fungal infections requiring treatment.
• Patients with serious concurrent illness or psychological, familial, sociological, geographical, or other concomitant conditions that, in the opinion of the investigator, would not permit adequate follow-up and compliance with the study protocol.
• Use of any investigational agent within four weeks of study treatment.
• Prior gene therapy.
• History of myocardial infarction within 6 months, angina within the past 6 months, or a history of arrhythmias on active therapy.
• Patients who have received standard chemotherapy with FDA approved agents within 21 days of entry into the protocol.
• Patients who have received therapy with an oral tyrosine kinase inhibitor (eg, erlotinib) within 14 days prior to entry into the protocol.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Lu C, Stewart DJ, Lee JJ, Ji L, Ramesh R, Jayachandran G, Nunez MI, Wistuba II, Erasmus JJ, Hicks ME, Grimm EA, Reuben JM, Baladandayuthapani V, Templeton NS, McMannis JD, Roth JA. Phase I clinical trial of systemically administered TUSC2(FUS1)-nanoparticles mediating functional gene transfer in humans. PLoS One. 2012;7(4):e34833. doi: 10.1371/journal.pone.0034833. Epub 2012 Apr 25.

  PMID: 22558101 DERIVED

Related Links

• UT M.D.Anderson Cancer Center

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• David J. Stewart, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2003
• First Posted: April 30, 2003
• Study Start: March 1, 2003
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: February 23, 2012

Record last verified: 2012-02

Locations

US (1)