Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Mixed Glioma, Recurrent Glioblastoma
Conditions
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.
Interventions
Given via injection into resection cavity or around tumor bed and/or IT
OTHERLaboratory Biomarker Analysis
Correlative studies
PROCEDURETherapeutic Conventional Surgery
Undergo en bloc resection
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A (Resection Cavity) - Dose Level 1 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. | 4 |
| Arm A (Resection Cavity) - Dose Level 2 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. | 3 |
| Arm A (Resection Cavity) - Dose Level 3 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. | 3 |
| Arm B (Intratumoral/Resection Cavity) - Dose Level 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. | 3 |
| Arm B (Intratumoral/Resection Cavity) - Dose Level 2 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. | 10 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Cancellation | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Arm B (Intratumoral/Resection Cavity) - Dose Level 1 | Arm A (Resection Cavity) - Dose Level 3 | Arm A (Resection Cavity) - Dose Level 1 | Arm A (Resection Cavity) - Dose Level 2 | Arm B (Intratumoral/Resection Cavity) - Dose Level 2 |
|---|---|---|---|---|---|---|
| Age, Customized Age Group 40-60 years | 15 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 5 Participants |
| Age, Customized Age Group <40 years | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Customized Age Group >60 years | 6 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants |
| ECOG Performance Status 0 | 6 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| ECOG Performance Status 1 | 14 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| ECOG Performance Status 2 | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Female | 11 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 12 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 10 / 10 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 10 / 10 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 10 |
Outcome results
Primary
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.
Time frame: Up to 2 weeks
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A (Resection Cavity) - Dose Level 1 | Number of Patients Experiencing Grade 3+ Adverse Events, Per NCI CTCAE Version 3.0 | 6 Participants |
| Arm A (Resection Cavity) - Dose Level 2 | Number of Patients Experiencing Grade 3+ Adverse Events, Per NCI CTCAE Version 3.0 | 5 Participants |
Primary
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.
Time frame: 2 weeks
Population: Excludes cancel patient (never started treatment).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (Resection Cavity) - Dose Level 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 | 0 patients |
| Arm A (Resection Cavity) - Dose Level 2 | 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 | 0 patients |
| Arm A (Resection Cavity) - Dose Level 3 | 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 | 0 patients |
| Arm B (Intratumoral/Resection Cavity) - Dose Level 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 | 0 patients |
| Arm B (Intratumoral/Resection Cavity) - Dose Level 2 | 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 | 0 patients |
Secondary
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.
Time frame: Up to 2 weeks
Population: 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 | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A (Resection Cavity) - Dose Level 1 | Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence | SD | 8 Participants |
| Arm A (Resection Cavity) - Dose Level 1 | Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence | PD | 1 Participants |
| Arm A (Resection Cavity) - Dose Level 2 | Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence | SD | 12 Participants |
| Arm A (Resection Cavity) - Dose Level 2 | Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence | PD | 1 Participants |
Secondary
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.
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A (Resection Cavity) - Dose Level 1 | Progression-free Survival (PFS) | PFS at 3 months | 55.6 percentage of patients |
| Arm A (Resection Cavity) - Dose Level 1 | Progression-free Survival (PFS) | PFS at 6 months | 22.2 percentage of patients |
| Arm A (Resection Cavity) - Dose Level 2 | Progression-free Survival (PFS) | PFS at 3 months | 61.5 percentage of patients |
| Arm A (Resection Cavity) - Dose Level 2 | Progression-free Survival (PFS) | PFS at 6 months | 23.1 percentage of patients |
Secondary
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.
Time frame: Up to 13 years
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (Resection Cavity) - Dose Level 1 | Survival | 11.8 months |
| Arm A (Resection Cavity) - Dose Level 2 | Survival | 11.4 months |
p-value: 0.2895% CI: [0.67, 4.11]Log Rank
Other Pre-specified
CEA Titers
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
Other Pre-specified
Change in CD46 Status
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
Other Pre-specified
Change in CD4 Counts
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
Other Pre-specified
Change in CD8 Counts
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
Other Pre-specified
Change in Viral Shedding
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
Other Pre-specified
Change in Viremia
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
Other Pre-specified
Measles Virus Specific Immunity, in Terms of Change in Interferon Gamma
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
Other Pre-specified
Measles Virus Specific Immunity, in Terms of Change in Lymphoproliferative Assay Results
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
Other Pre-specified
Viral Propagation in Tumor
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