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Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme

Primary Purpose

Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Mixed Glioma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Carcinoembryonic Antigen-Expressing Measles Virus

Laboratory Biomarker Analysis

Therapeutic Conventional Surgery

About this trial

This is an interventional treatment trial for Anaplastic Astrocytoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Recurrent grade 3 or 4 glioma, including astrocytoma, oligodendroglioma or mixed glioma with histologic confirmation at initial diagnosis or recurrence
Candidate for gross total or subtotal resection
Absolute neutrophil count (ANC) >= 1500/uL
Platelets (PLT) >= 100,000/uL
Total bilirubin =< 1.5 x upper normal limit (ULN)
Aspartate aminotransferase (AST) =< 2 x ULN
Creatinine =< 2.0 x ULN
Hemoglobin (Hgb) >= 9.0 gm/dL
Prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.3 x ULN
Ability to provide informed consent
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
Anti-measles virus immunity as demonstrated by immunoglobulin G (IgG) anti-measles antibody levels of >= 1.1 EU/ml as determined by enzyme immunoassay
Normal serum CEA levels (< 3 ng/ml) at the time of registration
Willing to provide biologic specimens as required by the protocol
Negative serum pregnancy test done =< 7 days prior to registration (for women of childbearing potential only)

Exclusion Criteria:

Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
Active infection =< 5 days prior to registration
History of tuberculosis or history of purified protein derivative (PPD) positivity
Any of the following therapies:
- Chemotherapy =< 4 weeks prior to registration (6 wks for nitrosourea-based chemotherapy)
- Immunotherapy =< 4 weeks prior to registration
- Biologic therapy =< 4 weeks prior to registration
- Bevacizumab =< 12 weeks prior to registration
- Non-cytotoxic antitumor drugs, i.e., small molecule cell cycle inhibitors =< 2 weeks prior to registration
- Radiation therapy =< 6 weeks prior to registration
- Any viral or gene therapy prior to registration
Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
New York Heart Association classification III or IV
Requiring blood product support
Inadequate seizure control
Expected communication between ventricles and resection cavity as a result of surgery
Human immunodeficiency virus (HIV)-positive test result, or history of other immunodeficiency
History of organ transplantation
History of chronic hepatitis B or C
Other concurrent chemotherapy, immunotherapy, radiotherapy or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
Exposure to household contacts =< 15 months old or household contact with known immunodeficiency
Allergy to measles vaccine or history of severe reaction to prior measles vaccination

Sites / Locations

Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm A (resection cavity administration)

Arm B (intratumoral and resection cavity administration)

Arm Description

Patients undergo en block resection of their tumor (after confirming diagnosis) on day 1, followed by MV-CEA administered into the resection cavity.

Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by MV-CEA IT through the catheter over 10 minutes on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques on day 5, followed by MV-CEA administered around the tumor bed.

Outcomes

Primary Outcome Measures

Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I) Maximum Tolerated Dose (MTD) (Phase I) as Measured by the Number of Participants With Dose Limiting Toxicities

The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include hematologic events grade 3 or higher (except grade 3 ANC lasting < 72 hours), non-hematologic events graded 3 or higher (except grade 3 nausea, vomiting, or diarrhea were to be considered DLT only if patient was receiving the max supportive care and alopecia was not considered dose limiting), neurologic toxicity grade 2 or higher, grade 2 allergic reactions asymptomatic bronchospasm and/or urticarial, grade 3 or higher allergic reactions, viremia lasting for 6 weeks or more from last viral administration deemed at least possibly related to treatment. The number of patients reporting a dose-limiting event are reported.

Number of Patients Experiencing Grade 3+ Adverse Events, Per NCI CTCAE Version 3.0

The number of patients experiencing grade 3+ adverse events (overall and by arm) will be tabulated and summarized in this patient population.

Secondary Outcome Measures

Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence

The number of responses will be summarized by simple descriptive summary statistics delineating response type. CR = total disappearance of all tumor with patient off corticosteroids or only on adrenal replacement maintenance. PR= 50% reduction in product of perpendicular diameters of contrast enhancement or mass with no new lesions with the patient being on stable or decreased steroid dose. REGR = unequivocal reduction in size of contrast-enhancement or decrease in mass effect as agreed upon independently by primary physician and quality control physicians; no new lesions. SD = failure to qualify for CR, PR, REGR, or PROG. PROG = >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions and/or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions.

Progression-free Survival (PFS)

Percentage of patients who are progression free at 3 and 6 months (PFS3 and PFS6) will be summarized descriptively. Progression-free survival is defined as the length of time from date of registration to a) date of progression or death due to any cause or b) last follow-up. Progression is defined as a >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions, and/or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions.

Survival

Overall survival is defined as the length of time from date of registration to a) death due to any cause or b) last follow-up. Reported using standard Kaplan-Meier estimation method.

Full Information

NCT ID

NCT00390299

First Posted

October 18, 2006

Last Updated

December 31, 2019

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00390299

Brief Title

Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme

Official Title

Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme (GBM)

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

October 23, 2006 (Actual)

Primary Completion Date

November 29, 2018 (Actual)

Study Completion Date

November 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This phase I trial studies the side effects and best dose of carcinoembryonic antigen-expressing measles virus (MV-CEA) in treating patients with glioblastoma multiforme that has come back. A virus, called MV-CEA, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells.

Detailed Description

PRIMARY OBJECTIVES: I. To assess the safety and toxicity of intratumoral and resection cavity administration of an Edmonston's strain measles virus genetically engineered to produce CEA (MV-CEA) in patients with recurrent glioblastoma multiforme. II. To determine the maximum tolerated dose (MTD) of MV-CEA. III. To characterize viral gene expression at each dose level as manifested by CEA titers. IV. To assess viremia, viral replication, and measles virus shedding/persistence following intratumoral administration. V. To assess humoral and cellular immune response to the injected virus. VI. To assess in a preliminary fashion antitumor efficacy of this approach. OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 sequential treatment arms. ARM A (RESECTION CAVITY ADMINISTRATION): Patients undergo en block resection of their tumor (after confirming diagnosis) on day 1, followed by MV-CEA administered into the resection cavity. ARM B (INTRATUMORAL AND RESECTION CAVITY ADMINISTRATION): Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by carcinoembryonic antigen-expressing measles virus intratumorally (IT) through the catheter over 10 minutes on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques on day 5, followed by MV-CEA administered around the tumor bed. After completion of study treatment, patients are followed up at 28 days (non-cohort I patients), 7 weeks (patients in cohort I only), every 2 months until progression, every 3 and 12 months after progression, and then yearly thereafter for up to 15 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Mixed Glioma, Recurrent Glioblastoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A (resection cavity administration)

Arm Type

Experimental

Arm Description

Patients undergo en block resection of their tumor (after confirming diagnosis) on day 1, followed by MV-CEA administered into the resection cavity.

Arm Title

Arm B (intratumoral and resection cavity administration)

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Carcinoembryonic Antigen-Expressing Measles Virus

Other Intervention Name(s)

MV-CEA

Intervention Description

Given via injection into resection cavity or around tumor bed and/or IT

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Procedure

Intervention Name(s)

Therapeutic Conventional Surgery

Intervention Description

Undergo en bloc resection

Primary Outcome Measure Information:

Title

Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I) Maximum Tolerated Dose (MTD) (Phase I) as Measured by the Number of Participants With Dose Limiting Toxicities

Description

Time Frame

2 weeks

Title

Number of Patients Experiencing Grade 3+ Adverse Events, Per NCI CTCAE Version 3.0

Description

The number of patients experiencing grade 3+ adverse events (overall and by arm) will be tabulated and summarized in this patient population.

Time Frame

Up to 2 weeks

Secondary Outcome Measure Information:

Title

Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence

Description

Time Frame

Up to 2 weeks

Title

Progression-free Survival (PFS)

Description

Time Frame

Length of time from date of registration to a) date of progression or death due to any cause or b) last follow-up, assessed up to 6 months

Title

Survival

Description

Overall survival is defined as the length of time from date of registration to a) death due to any cause or b) last follow-up. Reported using standard Kaplan-Meier estimation method.

Time Frame

Up to 13 years

Other Pre-specified Outcome Measures:

Title

CEA Titers

Description

Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlates between these laboratory values and other outcome measures like response and dose levels will be carried out in an exploratory manner.

Time Frame

Up to 15 years

Title

Change in CD4 Counts

Description

Time Frame

Baseline to day 28

Title

Change in CD46 Status

Description

Time Frame

Baseline to up to day 5

Title

Change in CD8 Counts

Description

Time Frame

Baseline to day 28

Title

Change in Viral Shedding

Description

Time Frame

Baseline to day 28

Title

Change in Viremia

Description

Time Frame

Baseline to up to 15 years

Title

Measles Virus Specific Immunity, in Terms of Change in Interferon Gamma

Description

Time Frame

Baseline to day 28

Title

Measles Virus Specific Immunity, in Terms of Change in Lymphoproliferative Assay Results

Description

Time Frame

Baseline to day 28

Title

Viral Propagation in Tumor

Description

Time Frame

Up to day 5

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Recurrent grade 3 or 4 glioma, including astrocytoma, oligodendroglioma or mixed glioma with histologic confirmation at initial diagnosis or recurrence Candidate for gross total or subtotal resection Absolute neutrophil count (ANC) >= 1500/uL Platelets (PLT) >= 100,000/uL Total bilirubin =< 1.5 x upper normal limit (ULN) Aspartate aminotransferase (AST) =< 2 x ULN Creatinine =< 2.0 x ULN Hemoglobin (Hgb) >= 9.0 gm/dL Prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.3 x ULN Ability to provide informed consent Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 Anti-measles virus immunity as demonstrated by immunoglobulin G (IgG) anti-measles antibody levels of >= 1.1 EU/ml as determined by enzyme immunoassay Normal serum CEA levels (< 3 ng/ml) at the time of registration Willing to provide biologic specimens as required by the protocol Negative serum pregnancy test done =< 7 days prior to registration (for women of childbearing potential only) Exclusion Criteria: Any of the following: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception Active infection =< 5 days prior to registration History of tuberculosis or history of purified protein derivative (PPD) positivity Any of the following therapies: Chemotherapy =< 4 weeks prior to registration (6 wks for nitrosourea-based chemotherapy) Immunotherapy =< 4 weeks prior to registration Biologic therapy =< 4 weeks prior to registration Bevacizumab =< 12 weeks prior to registration Non-cytotoxic antitumor drugs, i.e., small molecule cell cycle inhibitors =< 2 weeks prior to registration Radiation therapy =< 6 weeks prior to registration Any viral or gene therapy prior to registration Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment New York Heart Association classification III or IV Requiring blood product support Inadequate seizure control Expected communication between ventricles and resection cavity as a result of surgery Human immunodeficiency virus (HIV)-positive test result, or history of other immunodeficiency History of organ transplantation History of chronic hepatitis B or C Other concurrent chemotherapy, immunotherapy, radiotherapy or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) Exposure to household contacts =< 15 months old or household contact with known immunodeficiency Allergy to measles vaccine or history of severe reaction to prior measles vaccination

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Evanthia Galanis

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme

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