Gene Therapy Clinical Trials

Gene Therapy for Pleural Malignancies

Ad.hIFN-β (BG00001) is a replication-defective recombinant adenoviral vector containing the human interferon-beta (hIFN-β) gene. This Phase I study is designed to evaluate the safety and maximum tolerated dose (MTD) of two doses of intrapleural (IP) Ad.hIFN-β in subjects with pleural malignancies either metastatic or pleural mesothelioma. This Phase I study will evaluate the safety of two doses of BG00001. Eligible subjects will have:

malignant pleural mesothelioma, or
pleural effusions who have progressed through at least one prior therapy or have refused therapy

BG00001 is given twice, on Day 1 and Day 15. BG00001 is given through a catheter in the pleural space. [More information.]

Abramson Cancer Center of the University of Pennsylvania
Biogen Idec, Incorporated
Daniel H. Sterman, M.D. Principal Investigator
Adri Recio, RN
Ph: 215-573-6760
Email: arecio@mail.med.upenn.edu

Phase I clinical study of the treatment of malignant pleural mesothelioma with gene modified cancer cells.

Malignant mesothelioma is a tumor of the pleura for which there is no satisfactory treatment. It is almost universally fatal, regardless of the stage of the tumor at the time of diagnosis. Current treatment modalities include surgery, chemotherapy, and radiation therapy, although in some series none of these modalities is superior to no treatment at all. Because of the dismal prognosis for patients with malignant mesothelioma, a new mode of treatment is desperately needed.

A promising area of research into the treatment of various malignancies is gene therapy. Recent studies have demonstrated the utility of exposing tumor cells to cells transduced to express the Herpes simplex virus gene for thymidine kinase (HSV-TK). By virtue of their expression of HSV-TK, the transduced cells are rendered susceptible to the antiviral drug, ganciclovir (GCV). Nearby tumor cells are killed by a so-called bystander effect. In this protocol we propose a Phase I trial to study the safety and determine the maximal tolerated dose of an HSV-TK-transduced ovarian cancer cell line (PA1-STK cells) infused into the pleural cavities of patients with malignant pleural mesothelioma, followed by systemic administration of ganciclovir. The hope is that administration of ganciclovir will result in killing of the transduced ovarian cancer cells as well as the nearby malignant mesothelioma cells. This is a standard dose-escalation protocol.

Gene Therapy Laboratory
Louisiana State University Health Sciences Center
533 Bolivar Street, Room 601
New Orleans, LA 70112
Phone: (504) 568-6151
Fax: (504) 568-8500
E-mail: jkolls@lsuhsc.edu

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A Study of Intrapleural Gene Transfer for Pleural Malignancies - Lung Cancer

Purpose: To assess the safety and toxicity of intrapleural Ad.hIFN-beta in pts with MPM/MPE. To determine the maximum tolerated dose of intrapleural Ad.hIFN-beta delivered in a dose escalation fashion. To evaluate for successful gene transfer/IFN-beta gene expression.

This study involves the use of a new experimental type of technology called "gene transfer" that may eventually be useful in the treatment of pleural cancers. Gene transfer involves inserting a specially designed "gene" into cancer cells so they will produce an anti-cancer compound. The gene is first placed in a carrier or delivery system (in this case, the common-cold virus is used as the carrier). The virus, which has been altered so that it cannot grow in people, has a gene inserted into it. This virus, with the new gene in it, is then used to infect the cancer cells. Once inside the cancer cells, the gene becomes the blueprint for the production of a new protein. The new protein can be used to help destroy the cancer.

This research study will use a protein called interferon-beta (IFN-beta) to activate the immune system to help fight cancer. Interferons are natural compounds that the body makes in response to infections from viruses. These compounds make the body's immune response stronger and can hopefully help the body to "reject" the tumor. This type of gene transfer has been studied in mice, but is still experimental in humans. It is not known if the tumors will shrink with this experimental agent.

Procedure: A small catheter is placed between the lung and the chest wall (the pleural space). This catheter is used to drain cancerous fluid from the lung and to instill the gene into the pleural space. The catheter will remain in place for 6-8 weeks, during the study. The patient will be admitted to the hospital for approximately 3 days in order to receive the gene. The researchers will continue to see and evaluate the patient's response to the gene for six months.

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Phase II Gene Therapy Study in Patients with Malignant Pleural or Peritoneal Mesothelioma using rAd/p53 in Combination with Chemotherapy

Eligibility Requirements:

Patients with peritoneal or pleural mesothelioma
Prior chemotherapy/prior surgery permitted.
Evidence of p53 gene mutation will be assessed

Patients will be treated for three cycles with multiple intrapleural or intraperitoneal injections of rAd/p53 in combination with intravenous cisplatin. These treatments will take place at twenty-eight day intevals.

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Phase I Study of Decitabine Mediated Induction of Tumor Antigen and Tumor Suppressor Gene Expression in Patients with Cancers Involving the Lung, Esophagus, or Pleura

In preclinical studies, we have demonstrated induction of tumor antigen and tumor suppressor gene expression in lung and esophageal cancer cells as well as malignant pleural mesothelioma cells following DNA hypomethylation using decitabine concentrations which are potentially achievable in clinical settings. In order to assess the feasibility of DNA hypomethylation in solid tumors, patients with inoperable thoracic malignancies will receive two cycles of 72-hour intravenous infusion of decitabine using a phase I study design. Pharmacokinetics, systemic toxicity, and response to therapy will be recorded. Tumor biopsies will be obtained prior to, and after therapy to determine if expression of the NY-ESO-1 cancer testis antigen can be induced by demethylation mechanisms in vivo. Additional analysis will be undertaken to determine if immune recognition of this tumor antigen can be demonstrated following decitabine treatment. Furthermore, because approximately 40% of lung cancers exhibit inactivation of the Rb/CDKN2 pathway by hypermethylation, additional experiments will be undertaken to evaluate the pharmacokinetics for induction of this tumor suppressor pathway in vivo. Results of these studies may enable evaluation of additional agents which are known to facilitate transcription by demethylation or chromatin remodeling mechanisms.

Maryland
National Cancer Institute (NCI), 9000 Rockville Pike, Bethesda, Maryland, 20892, United States;

Recruiting
Clinical Studies Support Center/NCI 1-888-624-1937 ncicssc@mail.nih.gov

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Phase I Study of Gene Induction Mediated by Sequential Decitabine/Depsipeptide Infusion in Patients with Pulmonary and Pleural Malignancies

Preliminary research indicates that the drug decitabine (DAC) enhances the immune response to tumors and may enable the p16 gene, called the 'suppressor gene,' to function normally. The drug depsipeptide (DP) appears to help kill cancer cells and prevent the growth of new cancer cells. These two drugs have been administered separately in the past. This study will examine the effect of the two drugs when they are given together.

The study will enroll 42 patients with lung cancer. Pregnant or nursing women and patients with HIV will not be enrolled. An arterial blood gas test, an EKG, x-rays and scans, pulmonary function tests, HIV blood testing, and a baseline biopsy will be performed to determine patient eligibility. Each patient will receive up to two 34-day cycles of treatment with DAC and DP. The second cycle will begin 35 days after the first one ends. Patients who show improvement may be offered further treatments. Patients who experience severe adverse effects will be withdrawn from the study.

A total of four tumor biopsies will be performed on each patient: one before treatment begins, one on day 5 of the first cycle, one before the second cycle, and one on day 5 of the second cycle. Depending on the location of the tumor, biopsies will be done either by bronchoscopy or needle aspiration.

The drugs will be administered through a central venous catheter. Patients will be hospitalized for 5 to 6 days to receive the treatment. First, DAC will be administered for 72 hours. On day 4, DP will be given over a period of 4 hours. Different patients will receive different doses of DP to help determine safe doses. Frequent blood tests will be done to monitor the drugs' effects. Blood tests will also be done on days 8, 10, 11, 14, 18, 21, 28, and 34 of each cycle. Because DP affects the heart, patients will wear a heart monitor while receiving the first dose, and will have up to six EKGs during the first dose and up to four EKGs during the second dose. One month after each cycle, a follow-up x-ray, blood test, and scans of the chest, abdomen, pelvis, and brain will be done to help evaluate response to the treatment.

Maryland
National Cancer Institute (NCI), 9000 Rockville Pike, Bethesda, Maryland, 20892, United States; Recruiting
Tricia Kunst, R.N. 3014024399 kunstt@mail.nih.gov

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Intrapleural BG00001 in Treating Patients With Malignant Pleural Mesothelioma or Malignant Pleural Effusions

RATIONALE: Using BG00001 to insert the gene for interferon-beta into a person's pleural cavity may improve the body's ability to fight cancer.

PURPOSE: Phase I trial to study the effectiveness of intrapleural BG00001 in treating patients who have malignant pleural mesothelioma or malignantpleural effusions.

Pennsylvania
Abramson Cancer Center at University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, 19104, United States.

Recruiting
Adri Recio, RN 215-573-6760

Study chairs or principal investigators
Daniel H. Sterman, MD, Study Chair, University of Pennsylvania Cancer Center

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PV701 in Treating Patients With Advanced or Recurrent Peritoneal Cancer

RATIONALE: PV701 may be able to kill tumor cells while leaving normal cells undamaged.

PURPOSE: Phase I trial to study the effectiveness of PV701 in treating patients who have advanced or recurrentovarian epithelial, fallopian tube, primaryperitoneal, colorectal, or other cancer found primarily within the peritoneal cavity.

New York
Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States;

Recruiting
David R. Spriggs, MD 212-639-2203

Study chairs or principal investigators
David R. Spriggs, MD, Study Chair, Memorial Sloan-Kettering Cancer Center

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Gene Therapy Clinical Trials