Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00390299
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 23
• Location: 1
• Arms: 2
• Actual Duration (Months): 157.2
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Mixed Glioma; Recurrent Glioblastoma	Biological: Carcinoembryonic Antigen-Expressing Measles Virus; Other: Laboratory Biomarker Analysis; Procedure: Therapeutic Conventional Surgery	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

2. 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.

3. To assess viremia, viral replication, and measles virus shedding/persistence following intratumoral administration.

4. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme (GBM)
• Actual Study Start Date: Oct 23, 2006
• Actual Primary Completion Date: Nov 29, 2018
• Actual Study Completion Date: Nov 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: Carcinoembryonic Antigen-Expressing Measles Virus; Given via injection into resection cavity or around tumor bed and/or IT; Other Names: MV-CEA ; Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Therapeutic Conventional Surgery; Undergo en bloc resection
Experimental: 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 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.	Biological: Carcinoembryonic Antigen-Expressing Measles Virus; Given via injection into resection cavity or around tumor bed and/or IT; Other Names: MV-CEA ; Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Therapeutic Conventional Surgery; Undergo en bloc resection

Outcome Measures

Primary Outcome Measures

1. 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 [2 weeks]

   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.

2. Number of Patients Experiencing Grade 3+ Adverse Events, Per NCI CTCAE Version 3.0 [Up to 2 weeks]

   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

1. Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence [Up to 2 weeks]

   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.

2. Progression-free Survival (PFS) [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]

   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.

3. Survival [Up to 13 years]

   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.

Other Outcome Measures

1. CEA Titers [Up to 15 years]

   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.

2. Change in CD4 Counts [Baseline to day 28]

   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.

3. Change in CD46 Status [Baseline to up to day 5]

   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.

4. Change in CD8 Counts [Baseline to day 28]

   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.

5. Change in Viral Shedding [Baseline to day 28]

   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.

6. Change in Viremia [Baseline to up to 15 years]

   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.

7. Measles Virus Specific Immunity, in Terms of Change in Interferon Gamma [Baseline to day 28]

   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.

8. Measles Virus Specific Immunity, in Terms of Change in Lymphoproliferative Assay Results [Baseline to day 28]

   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.

9. Viral Propagation in Tumor [Up to day 5]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Evanthia Galanis, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 9, 2016

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00390299
• Other Study ID Numbers: MC0671; NCI-2009-01198; MC0671; P30CA015083; P50CA108961
• First Posted: Oct 19, 2006
• Last Update Posted: Jan 2, 2020
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Glioblastoma; Astrocytoma; Oligodendroglioma; Glioma; Recurrence

Study Results

Participant Flow

Arm/Group Title	Arm A (Resection Cavity) - Dose Level 1	Arm A (Resection Cavity) - Dose Level 2	Arm A (Resection Cavity) - Dose Level 3	Arm B (Intratumoral/Resection Cavity) - Dose Level 1	Arm B (Intratumoral/Resection Cavity) - Dose Level 2
Arm/Group Description	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by 10^5 TCID50 MV-CEA administered into the resection cavity on day 1.	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by 10^6 TCID50 MV-CEA administered into the resection cavity on day 1.	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by 10^7 TCID50 MV-CEA administered into the resection cavity on day 1.	Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by intratumoral administration of 10^6 TCID50 MV-CEA on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques followed by injection of 10^6 TCID50 MV-CEA in resection cavity on day 5.	Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by intratumoral administration of 10^7 TCID50 MV-CEA on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques followed by injection of 10^7 TCID50 MV-CEA in resection cavity on day 5.
Period Title: Overall Study
STARTED	4	3	3	3	10
COMPLETED	3	3	3	3	10
NOT COMPLETED	1	0	0	0	0

Baseline Characteristics

Arm/Group Title	Arm A (Resection Cavity) - Dose Level 1	Arm A (Resection Cavity) - Dose Level 2	Arm A (Resection Cavity) - Dose Level 3	Arm B (Intratumoral/Resection Cavity) - Dose Level 1	Arm B (Intratumoral/Resection Cavity) - Dose Level 2	Total
Arm/Group Description	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by 10^5 TCID50 MV-CEA administered into the resection cavity on day 1.	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by 10^6 TCID50 MV-CEA administered into the resection cavity on day 1.	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by 10^7 TCID50 MV-CEA administered into the resection cavity on day 1.	Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by intratumoral administration of 10^6 TCID50 MV-CEA on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques followed by injection of 10^6 TCID50 MV-CEA in resection cavity on day 5.	Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by intratumoral administration of 10^7 TCID50 MV-CEA on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques followed by injection of 10^7 TCID50 MV-CEA in resection cavity on day 5.	Total of all reporting groups
Overall Participants	4	3	3	3	10	23
Age, Customized (Count of Participants)
<40 years	1 25%	0 0%	0 0%	0 0%	1 10%	2 8.7%
40-60 years	3 75%	2 66.7%	3 100%	2 66.7%	5 50%	15 65.2%
>60 years	0 0%	1 33.3%	0 0%	1 33.3%	4 40%	6 26.1%
Sex: Female, Male (Count of Participants)
Female	0 0%	1 33.3%	1 33.3%	1 33.3%	8 80%	11 47.8%
Male	4 100%	2 66.7%	2 66.7%	2 66.7%	2 20%	12 52.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	4 100%	3 100%	3 100%	3 100%	10 100%	23 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
ECOG Performance Status (Count of Participants)
0	1 25%	1 33.3%	1 33.3%	0 0%	3 30%	6 26.1%
1	3 75%	1 33.3%	2 66.7%	2 66.7%	6 60%	14 60.9%
2	0 0%	1 33.3%	0 0%	1 33.3%	1 10%	3 13%

Outcome Measures

1. Primary Outcome

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	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.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Excludes cancel patient (never started treatment).

Arm/Group Title	Arm A (Resection Cavity) - Dose Level 1	Arm A (Resection Cavity) - Dose Level 2	Arm A (Resection Cavity) - Dose Level 3	Arm B (Intratumoral/Resection Cavity) - Dose Level 1	Arm B (Intratumoral/Resection Cavity) - Dose Level 2
Arm/Group Description	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by 10^5 TCID50 MV-CEA administered into the resection cavity on day 1.	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by 10^6 TCID50 MV-CEA administered into the resection cavity on day 1.	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by 10^7 TCID50 MV-CEA administered into the resection cavity on day 1.	Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by intratumoral administration of 10^6 TCID50 MV-CEA on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques followed by injection of 10^6 TCID50 MV-CEA in resection cavity on day 5.	Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by intratumoral administration of 10^7 TCID50 MV-CEA on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques followed by injection of 10^7 TCID50 MV-CEA in resection cavity on day 5.
Measure Participants	3	3	3	3	10
Number [patients]	0	0	0	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Resection Cavity) - Dose Level 1, Arm A (Resection Cavity) - Dose Level 2, Arm A (Resection Cavity) - Dose Level 3
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Maximum Tolerated Dose (x 10^7 TCID50)
	Estimated Value	1
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Intratumoral/Resection Cavity) - Dose Level 1, Arm B (Intratumoral/Resection Cavity) - Dose Level 2
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Maximum Tolerated Dose (x 10^7 TCID50)
	Estimated Value	1
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Per protocol analysis population; excludes cancel patient (never started treatment). Per section 16.2 of the protocol, this analysis will be performed by arm (for Arms A and B).

Arm/Group Title	Arm A (Resection Cavity Administration)	Arm B (Intratumoral and Resection Cavity Administration)
Arm/Group Description	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by MV-CEA administered into the resection cavity on day 1.	Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by intratumoral administration of MV-CEA on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques followed by injection of MV-CEA in resection cavity on day 5.
Measure Participants	9	13
Count of Participants [Participants]	6 150%	5 166.7%

3. Secondary Outcome

Title	Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence
Description	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.
Time Frame	Up to 2 weeks

Outcome Measure Data

Analysis Population Description

Per protocol analysis population; excludes cancel patient (never started treatment). Per section 16.2 of the protocol, this analysis will be performed by arm (for Arms A and B).

Arm/Group Title	Arm A (Resection Cavity Administration)	Arm B (Intratumoral and Resection Cavity Administration)
Arm/Group Description	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by MV-CEA administered into the resection cavity on day 1.	Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by intratumoral administration of MV-CEA on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques followed by injection of MV-CEA in resection cavity on day 5.
Measure Participants	9	13
SD	8 200%	12 400%
PD	1 25%	1 33.3%

4. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	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.
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

Outcome Measure Data

Analysis Population Description

Per protocol analysis population; excludes cancel patient (never started treatment). Per section 16.2 of the protocol, this analysis will be performed by arm (for Arms A and B).

Arm/Group Title	Arm A (Resection Cavity Administration)	Arm B (Intratumoral and Resection Cavity Administration)
Arm/Group Description	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by MV-CEA administered into the resection cavity on day 1.	Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by intratumoral administration of MV-CEA on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques followed by injection of MV-CEA in resection cavity on day 5.
Measure Participants	9	13
PFS at 3 months	55.6	61.5
PFS at 6 months	22.2	23.1

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Per protocol analysis population; excludes cancel patient (never started treatment). Per section 16.2 of the protocol, this analysis will be performed by arm (for Arms A and B).

Arm/Group Title	Arm A (Resection Cavity Administration)	Arm B (Intratumoral and Resection Cavity Administration)
Arm/Group Description	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by MV-CEA administered into the resection cavity on day 1.	Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by intratumoral administration of MV-CEA on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques followed by injection of MV-CEA in resection cavity on day 5.
Measure Participants	9	13
Median (95% Confidence Interval) [months]	11.8	11.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Resection Cavity) - Dose Level 1, Arm A (Resection Cavity) - Dose Level 2
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.66
	Confidence Interval	(2-Sided) 95%; 0.67 to 4.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Change in CD4 Counts
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	Baseline to day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	Change in CD46 Status
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	Baseline to up to day 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Change in CD8 Counts
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	Baseline to day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Change in Viral Shedding
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	Baseline to day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Other Pre-specified Outcome

Title	Change in Viremia
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	Baseline to up to 15 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Other Pre-specified Outcome

Title	Measles Virus Specific Immunity, in Terms of Change in Interferon Gamma
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	Baseline to day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Other Pre-specified Outcome

Title	Measles Virus Specific Immunity, in Terms of Change in Lymphoproliferative Assay Results
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	Baseline to day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Other Pre-specified Outcome

Title	Viral Propagation in Tumor
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 day 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to 2 weeks
Adverse Event Reporting Description	All patients who received treatment were assessed at the end of two weeks for adverse events.
Arm/Group Title	Arm A (Resection Cavity) - Dose Level 1		Arm A (Resection Cavity) - Dose Level 2		Arm A (Resection Cavity) - Dose Level 3		Arm B (Intratumoral/Resection Cavity) - Dose Level 1		Arm B (Intratumoral/Resection Cavity) - Dose Level 2
Arm/Group Description	Patients undergo en block resection of their tumor (after confirming diagnosis) followed by 10^5 TCID50 MV-CEA administered into the resection cavity on day 1.		Patients undergo en block resection of their tumor (after confirming diagnosis) followed by 10^6 TCID50 MV-CEA administered into the resection cavity on day 1.		Patients undergo en block resection of their tumor (after confirming diagnosis) followed by 10^7 TCID50 MV-CEA administered into the resection cavity on day 1.		Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by intratumoral administration of 10^6 TCID50 MV-CEA on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques followed by injection of 10^6 TCID50 MV-CEA in resection cavity on day 5.		Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by intratumoral administration of 10^7 TCID50 MV-CEA on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques followed by injection of 10^7 TCID50 MV-CEA in resection cavity on day 5.
All Cause Mortality
	Arm A (Resection Cavity) - Dose Level 1		Arm A (Resection Cavity) - Dose Level 2		Arm A (Resection Cavity) - Dose Level 3		Arm B (Intratumoral/Resection Cavity) - Dose Level 1		Arm B (Intratumoral/Resection Cavity) - Dose Level 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		10/10 (100%)
Serious Adverse Events
	Arm A (Resection Cavity) - Dose Level 1		Arm A (Resection Cavity) - Dose Level 2		Arm A (Resection Cavity) - Dose Level 3		Arm B (Intratumoral/Resection Cavity) - Dose Level 1		Arm B (Intratumoral/Resection Cavity) - Dose Level 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Arm A (Resection Cavity) - Dose Level 1		Arm A (Resection Cavity) - Dose Level 2		Arm A (Resection Cavity) - Dose Level 3		Arm B (Intratumoral/Resection Cavity) - Dose Level 1		Arm B (Intratumoral/Resection Cavity) - Dose Level 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		10/10 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased	2/3 (66.7%)	3	2/3 (66.7%)	2	2/3 (66.7%)	2	3/3 (100%)	6	8/10 (80%)	12
Gastrointestinal disorders
Colonic obstruction	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
General disorders
Fatigue	2/3 (66.7%)	3	1/3 (33.3%)	1	2/3 (66.7%)	6	3/3 (100%)	3	7/10 (70%)	17
Localized edema	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1
Infections and infestations
Pneumonia(gr 3/4 ANC)	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0
Investigations
Leukocyte count decreased	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/10 (10%)	1
Lymphocyte count decreased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	3/10 (30%)	3
Neutrophil count decreased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1
Platelet count decreased	0/3 (0%)	0	1/3 (33.3%)	2	1/3 (33.3%)	2	2/3 (66.7%)	2	4/10 (40%)	7
Metabolism and nutrition disorders
Hyperglycemia	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0	0/10 (0%)	0
Nervous system disorders
Ataxia	2/3 (66.7%)	6	1/3 (33.3%)	2	1/3 (33.3%)	1	1/3 (33.3%)	3	1/10 (10%)	3
Depressed level of consciousness	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1
Headache	1/3 (33.3%)	1	1/3 (33.3%)	2	2/3 (66.7%)	4	1/3 (33.3%)	1	4/10 (40%)	7
Peripheral motor neuropathy	2/3 (66.7%)	6	2/3 (66.7%)	3	1/3 (33.3%)	1	0/3 (0%)	0	1/10 (10%)	3
Peripheral sensory neuropathy	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	3	1/3 (33.3%)	1	0/10 (0%)	0
Pyramidal tract syndrome	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	2/10 (20%)	3
Seizure	2/3 (66.7%)	4	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	5/10 (50%)	7
Speech disorder	1/3 (33.3%)	1	1/3 (33.3%)	3	1/3 (33.3%)	3	2/3 (66.7%)	2	3/10 (30%)	6
Psychiatric disorders
Anxiety	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0
Confusion	1/3 (33.3%)	2	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/3 (33.3%)	2	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0
Vascular disorders
Thrombosis	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.