Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00390299

Purpose

RATIONALE: The measles virus, that has been changed in a certain way, may kill tumor cells without damaging normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of viral therapy in treating patients with recurrent glioblastoma multiforme.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Biological: carcinoembryonic antigen-expressing measles virus Genetic: fluorescence in situ hybridization Genetic: reverse transcriptase-polymerase chain reaction Other: immunohistochemistry staining method Other: immunologic technique Other: laboratory biomarker analysis Procedure: adjuvant therapy Procedure: conventional surgery Procedure: needle biopsy Procedure: neoadjuvant therapy	Phase 1

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
Official Title:	Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme (GBM)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Measles

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:

Adverse events profile, in terms of number and severity of all adverse events, as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Overall toxicity incidence and toxicity profile (by dose level, patient, and tumor site) as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Time until any treatment related toxicity [ Designated as safety issue: Yes ]
Time until treatment-related toxicity ≥ grade 3 [ Designated as safety issue: Yes ]
Time until hematologic nadirs (WBC, absolute neutrophil count, platelet count) [ Designated as safety issue: No ]
Maximum tolerated dose of vaccine as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Correlate viremia, human CEA titers, viral propagation in tumor, viral shedding, CD46 status, delayed-type hypersensitivity results, CD4 and CD8 counts, lymphoproliferative assay, and ELISPOT assay with response and toxicity [ Designated as safety issue: Yes ]
Viral gene expression at each dose level as assessed by CEA titer [ Designated as safety issue: No ]
Viremia following intratumoral administration of vaccine as assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) of peripheral blood mononuclear cells [ Designated as safety issue: No ]
Measles virus shedding/persistence following intratumoral administration of vaccine as assessed by RT-PCR [ Designated as safety issue: No ]
Viral replication following intratumoral administration of vaccine as assessed by in situ hybridization and Vero cell overlay [ Designated as safety issue: No ]

Secondary Outcome Measures:

CR, PR, regress, stable dis, & prog dis by neur exam, MRI, and/or CT scan for bidimens. meas. dis & eval dis. at baseline, 28 days after resection, and then every 2 mo. until progr. [ Designated as safety issue: No ]
Humoral and cell. imm. resp. by antimeasles virus-specific antibody level (IgG) at baseline, 28 days after resection, and every 2 mo until prog [ Designated as safety issue: No ]
Humoral and cell. imm. resp. by lymphoproliferative assay and interferon-gamma ELISPOT assay performed at baseline and at 28 days after tumor resection [ Designated as safety issue: No ]
Progression-free survival at 3 and 6 months [ Designated as safety issue: No ]
Time to disease progression [ Designated as safety issue: No ]
Time to treatment failure (due to progression, unacceptable toxicity, or refusal to continue participation by the patient) [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	October 2006
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the safety and toxicity of intratumoral and/or resection cavity administration of a recombinant, attenuated Edmonston B vaccine strain derivative of measles virus genetically engineered to produce human carcinoembryonic antigen (CEA) in patients with recurrent glioblastoma multiforme.
Determine the maximum tolerated dose of this oncolytic virus in these patients.
Determine viral gene expression at each dose level as manifested by CEA titers in patients treated with this oncolytic virus.
Assess viremia, viral replication, and measles virus shedding/persistence after intratumoral administration of this oncolytic virus.
Assess humoral and cellular immune response to the injected virus in these patients.

Secondary

Determine, preliminarily, the antitumor efficacy of this vaccine in these patients.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 sequential treatment groups.

Group 1 (resection cavity administration): Patients undergo en block resection of their tumor (after confirming diagnosis) on day 1, followed by recombinant measles virus encoding human carcinoembryonic antigen (MV-CEA) administered into the resection cavity over 10 minutes.
Group 2 (intratumoral and resection cavity administration): Patients undergo placement of a catheter within the tumor, followed by MV-CEA administration into the tumor through the catheter over 10 minutes on day 1. Patients undergo en block resection of their tumor with computer-assisted stereotactic techniques on day 5, followed by MV-CEA administered around the tumor bed.

In both groups, cohorts of 1-6 patients receive escalating doses of MV-CEA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD in group 1 has been determined, patients are assigned to group 2. The MTD in group 1 is used to determine the starting dose in group 2. At least 10 patients are treated at the MTD determined in group 2.

Biopsy specimen, resected tumor, normal tissue, and peripheral blood are collected during study for immunologic and biomarker correlative studies, including analysis of CD46 receptor levels (by immunohistochemistry [IHC]), measles virus N protein (by IHC), measles and viral gene expression and replication (by in situ hybridization), CEA monitoring (by immunoassay), measles virus N mRNA (by reverse transcriptase-polymerase chain reaction), and measles virus immunity. Assessments of immune competence and peripheral response to viral administration are also performed.

After completion of study treatment, patients are followed periodically for up to 15 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed grade 4 astrocytoma (glioblastoma multiforme) at primary diagnosis and/or recurrence
Recurrent disease
Candidate for gross total or subtotal resection
- No expected communication between ventricles and resection cavity as a result of surgery
Antimeasles virus immunity as demonstrated by IgG antimeasles antibody levels of ≥ 20 EU/mL as determined by enzyme immunoassay
Human carcinoembryonic antigen (CEA) < 3 ng/mL

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST ≤ 2 times ULN
Creatinine ≤ 2.0 times ULN
Hemoglobin ≥ 9.0 g/dL
PT and aPTT ≤ 1.3 times ULN
Willing to provide biological specimens as required by the study
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No active infection within the past 5 days
No history of tuberculosis or purified protein derivative positivity
No New York Heart Association class III or IV cardiac disease
Adequate seizure control
HIV negative
No history of other immunodeficiency
No history of chronic hepatitis B or C
No exposure (household contacts) to children ≤ 15 months of age or to people with known immunodeficiency
No allergy to measles vaccine or history of severe reaction to prior measles vaccination
No requirement for blood product support

PRIOR CONCURRENT THERAPY:

More than 4 weeks since prior chemotherapy (6 weeks for nitrosourea-based chemotherapy) and recovered
More than 4 weeks since prior immunotherapy
More than 4 weeks since prior biologic therapy
More than 2 weeks since prior noncytotoxic antitumor drugs (i.e., small molecule cell cycle inhibitors)
More than 6 weeks since prior radiotherapy
No prior viral or gene therapy
No history of organ transplantation
No concurrent chemotherapy, other immunotherapy, radiotherapy, or any other ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation)
No concurrent enrollment on any other study involving a pharmacologic agent (e.g., drugs, biologics), immunotherapy approaches, or gene therapy whether for symptom control or therapeutic intent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00390299

Locations

United States, Minnesota
Mayo Clinic Cancer Center	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:

Evanthia Galanis, MD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Evanthia Galanis, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier:	NCT00390299 History of Changes
Other Study ID Numbers:	CDR0000507615, P30CA015083, MC0671, 06-004440
Study First Received:	October 18, 2006
Last Updated:	April 18, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Mayo Clinic:

recurrent adult brain tumor
adult glioblastoma
adult gliosarcoma
adult giant cell glioblastoma

Additional relevant MeSH terms:

Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors

Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases

ClinicalTrials.gov processed this record on May 22, 2012